用户名: 密码: 验证码:
超频振动膜过滤技术在清开灵注射液药材金银花和栀子提取分离工艺中的应用研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
广东省名牌产品明兴清开灵注射液是一种中药注射液,处方由牛黄、珍珠母、水牛角、黄芩、栀子、金银花、板蓝根七味药组成。具有保护肝脏、促进损伤肝细胞的修复、清热解毒、镇静安神等功效。处方中的栀子、金银花、板蓝根的有效部位是分别利用水提醇沉和加热浓缩的方法制取浸膏而得到的,该法有耗醇、耗能、费时,效率低、成本高等不足,且得到的产品质量也常常不稳定。本课题拟用超频振动膜过滤技术代替醇沉和加热浓缩,期望能够节约乙醇、缩短生产周期,提高产品质量、提取效率和安全系数,并且能降低成本。
     超频振动膜过滤技术是运用机械的高频振动,在滤膜表面产生高剪切力的新型高效的“动态”膜分离和浓缩技术,与传统水提醇沉、加热浓缩工艺及一般“静态”膜过滤技术相比具有以下特点:
     1.滤膜不易堵塞和污染,膜的保存和再生工序简单,膜的使用寿命长;
     2.生产工序少,周期短,效率高,成本低,能耗低,安全指数高;
     3.常温操作,不需要添加有机试剂,尤其适合稳定性差的物质的分离纯化,产品质量稳定;
     4.适用范围广,适应性强,在实际生产中灵活性大,分离、浓缩过程可以连续地进行;
     本实验结果表明:在清开灵注射液药材金银花和栀子的提取分离浓缩工艺中,超频振动膜滤技术可替代目前广泛使用的水提醇沉和加热浓缩工艺。
     本课题采用超频振动膜过滤技术,以“明兴清开灵注射液”处方中主要中药组分——金银花和栀子为研究对象,分别对其有效成分进行提取、分离和浓缩,期望能够替代水提醇沉、加热浓缩工艺。实验采用正交试验设计,以膜有效通量、相对除杂率、药典规定的主要成分绿原酸和栀子苷收率等为指标,考察了药液pH值、药液浓度、乙醇浓度和不同孔径滤膜四种主要影响因素,最终得到一组最优过滤条件;在最优组合的基础上,分别以金银花和栀子水提液过滤前后及浓缩前后的性状、相对除杂率、绿原酸和栀子苷的收率为考察指标,比较超频振动膜过滤提取、分离、浓缩与水提醇沉和加热浓缩工艺的效果,并对前期的试验结果进一步验证。结果表明:对于金银花提取液来说,γ型孔径的膜,药液pH=3,药液浓度为0.05g/ml,不加乙醇的条件下有最好的过滤效果;而对于栀子提取液来说,γ型孔径的膜,药液pH=9,药液浓度为0.05g/ml,乙醇浓度为10%的条件下有最好的过滤效果;同时配合δ型脱水膜,能使分离、浓缩过程连续、高效地进行。实验数据分析及相关物料成本核算表明,超频振动膜滤技术显著优于传统水提醇沉、加热浓缩工艺。
     作为国际公认为20世纪末到21世纪中期最有发展前途的一项高新生产技术,膜分离已经成为世界各国研究的热点。本实验旨在将超频振动膜过滤技术这一先进的分离浓缩技术推广应用到中药生产中,替代目前广泛使用的醇沉分离和加热浓缩工艺以及“静态”膜过滤,并促进中药提取物的分离浓缩工艺现代化及产品的规范化、标准化。同时,通过试验探索符合中药生产领域的膜分离技术的新理论、新工艺,为目前中药生产中关键环节的工艺改革提供有效可行的方法和依据,解决目前制约膜分离技术在中药提取液分离浓缩工艺中应用的关键问题,深化膜分离技术的应用,为推动中药生产现代化尽一份力量。
MingXing QingKaiLing injection, a famous product in Guangdong Province, is a traditional Chinese medicine injection which consists of bezoar, Nacre, Buffalo Horn, Milkvetch Root, gardenia, honeysuckle and Isatis Root, with the effect of protecting liver, promoting the restoration of the injury liver cell and so on. For the gardenia, honeysuckle and Isatis Root, their active ingredients’extraction method is water extraction by alcohol sedimentation and heating concentraion, which is time-consuming, has low efficiency, consumes alcohol and energy, costs much money, pollutes the environment and the safety coefficient is low, Morever, the product’s quality is unstable frequently. The research uses vibratory shear enhanced processing membrance filtration technology to replace the alcohol precipitation, expecting to save the ethanol, reduct production cycle, improve extraction efficiency, safety coefficient, save the costs and so on.
     VESP is a new type and high-performance of dynamic membrane filtration and concentraion technology which uses high shearing force on the surface of membrane duing to mechanical high-frequency vibration. Compared with conventional water extraction by alcohol sedimentation and distillation to condense, it possesses a lot of good characteristics. It has a wide range of applications, has strong adaptability and great flexibility while it’s procedure of separation and concentration is able to be consecutively carried out, operating at room temperature and does not need to add organic reagents, it is very suitable for separating and purifying unsteady materials. Morever, its production working procedure is fewer, the cycle is shorter, But the efficiency and the security index is higher, the cost and the energy consumption is lower, also the filtrating membranes are comparatively difficult to be clogged and contaminated, membrance life span becomes longer. Quality of products will be promoted as well as fully got assured. The experimental result indicated that conventional water extraction by alcohol sedimentation and distillation to condense and generally static membrane filtration could be substituted by vibratory shear enhanced processing membrane filtration during purification and concentration of the honeysuckle and gardenia in Qingkailing injection.
     Using VESP and taking the MingXing QingKingLing injection’s major components of prescription - honeysuckle and gardenia as the research object, the research respectively extracted, separated and condensed the effective components of them, expecting that can substitute conventional water extraction by alcohol sedimentation and distillation to condense. orthogonal design chiefly applies on the test, taking the valid flux of membrane, relative removal rates of impurity, yield of the chlorogenic acid and gardenia glucoside as index, optimize the main influential factors including pore size of filtration membrane, concentration of physic liquor, pH of physic liquor and the alcohol concentration. satisfactory result were achieved by orthogonal design test. According to preceding optimal parameter array, vibratory shear enhanced processing membrane filtration was compared with conventional water extraction by alcohol sedimentation and distillation to condense through investigating the description, relative removal of impurity, yield of the chlorogenic acid and gardenia glucoside respectively before and after filtration, and confirmed the earlier’s test result. Experiment result showed that for the honeysuckle, in the condition of pH=3, solution concentration is 0.05g/ml, using the membraneγhad the best filtration effect, for the gardenia, in the condition of pH=9, solution concentration is 0.05g/ml, the alcohol concentration is 10%, using the membraneγhad the best filtration effect, combined with membraneδof pore size to dehydrate, a process of continuity and high efficiency in separation and concentration of effective ingredient was displayed on us. Experiment result and correlated materials cost audit make clear that vibratory shear enhanced processing membrane filtration strikingly outstrip conventional water extraction by alcohol sedimentation and distillation to condense.
     Regarded as a most promising high-tech production of the separation technology at the end of the 20th century to the mid-21st centurys, membrane separation technology has become a hot research in the countries of the world. The experiment ultilized the vibratory shear enhanced processing membrane filtration to extract, separate and condense the main active ingredient of the honeysuckle and gardenia in MingXing QingKingLing injection, aiming that can bring this advanced technology of the seperation and purification into traditional Chinese medicine production and substitute widely used the conventional water extraction by alcohol sedimentation and distillation to condense and generally static membrane filtration technique, promoting standardization of membrane separation process and product. Meantime, new theory and technique about membrane separation process is explored and referred to reform old key point of production of the traditional Chinese medicine. In addition, this research will help solve critical issue that limit application of membrane filtration technique in production of the traditional Chinese medicine and contribute our effort to promote modernization of traditional Chinese medicine production.
引文
[1] 宁慧青. 超滤膜分离技术在中药生产中的应用研究[J]. 山西化工,2003,23(3):9-12
    [2] Brad Culkin, Ann Plotkin, Michele Monroe. Solve Membrane Fouling Problems with High-Shear Filtration[J]. Chemical Engineering Progress, 1998, 94(1):29-33
    [3] Kazutalca Takata, Kaxuyoshi Yamamoto, Rulin Bianc. Removal of humic substances with vibratory shear enhanced processing membrane filtration[J]. Water Suppl, 2001, l(17): 29-35
    [4] 郑领英. 膜分离与分离膜[J]. 高分子通报, 1999, 9(3): 134-144
    [5] 郭瑞丽, 李玲.膜分离技术及其应用简介[J]. 新疆大学学报(自然科学版), 2003,20(4):410-413
    [6] 朱智清. 膜分离技术的发展及其工业应用[J]. 化工技术与开发, 2003, 32(1)19-21
    [7] 刘玉荣. 浅谈几种膜技术及其应用. 全国化工实用高新技术交流会, 成都, 全国化工实用高新技术交流会论文集. 200407:37-45
    [8] 潘晓鸥, 李健. 超滤法在中药分离、纯化工艺中的应用进展[J]. 华西医学, 2004, 19 (2):351-352
    [9] 郭立玮, 彭国平. 水醇法与膜分离法精制含山茱萸中药制剂的比较研究[J].中成药,1999, 21(2):59-61
    [10] 王世岭. 超滤法提取黄芩甙的探讨[J]. 中成药研究, 1988,15(5):8-9
    [11] 王世岭. 超滤法一次提取黄芩甙的研究[J]. 中成药,1994,16(3):2-3
    [12] 冯汉鸽. 麻黄碱的提取[J]. 时珍国药研究,1993, 4(1):32-33
    [13] 何 昌 生 . 超 滤 技 术 在 甜 菊 甙 生 产 过 程 中 的 应 用 [J]. 水 处 理 技术,1994.20(2):89.
    [14] 黄伟文, 朱婉珍. 超滤法制备中药注射液的质量研究[J]. 水处理技术, 1988,14 (2): 87-90
    [15] 郑志安, 周嘉秀. 应用工业型平板式超滤机制备大输液的初步研究[J]. 药学情报通讯, 1991, 9(1):53-56
    [16] 宋洪涛 . 超滤法改革复合当归注射液制备工艺研究 [J]. 药学情报杂志,1993.11(3):41.
    [17] 全山从. 以超滤法和水醇法制备补骨脂[J]. 中成药,1990.12(1):3
    [18] 胡奇芬,苏彦珍. 不同工艺对复方中药制剂中多糖含量的影响[J]. 中成药, 1990,12(11):6-7
    [19] 董波. 采用超滤法处理何首乌药液的初步研究[J]. 甘肃药学,1992,(1):29
    [20] 刘洪谦, 屈凌波, 贾金付, 等. 生脉饮口服液超滤技术研究[J]. 中草药,1996, 27(4): 209-211
    [21] 杨张渭, 陆晓峰. 人参精采用超滤工艺中试研究[J]. 中成药, 1994, 16(1): 4
    [22] 杨明, 刘小彬. 膜分离技术在中药制剂中的应用[J]. 世界科学技术, 2004, 16(2): 31-34
    [23] 郭立玮, 彭国平. 大孔树脂吸附与超滤联用对六味地黄丸中丹皮酚和马钱素含量的影响[J]. 南京中医药大学学报, 1999, 15(2): 86-87
    [24] Long D. Nghiem. Andrea I. Sch? fer. Fouling autopsy of hollow-fibre MF membranes in wastewater reclamation[J]. Desalination, 206.188.113-121
    [25] Bhave R. Inorganic Membranes[J]. Synthesis, Characteristics, and Applications, New York: Van Nostrand Reinhold, 1991.
    [26] 顾国维, 何义亮. 膜生物反应器在污水处理中的研究和应用[M]. 北京化学工业出版社,1999
    [27] McDonogh R.et al. Concentration Polarization and adsorption effects Incross-flowul trafiltration of proteins[J]. Desalination, 1990,79:217~231
    [28] Meirelesh M, Aimar P. Effects Of protein fouling on the apparent pore size distribution of sieving membrane[J]. J.mem.Sci,1991,56:13~28
    [29] Bhave R R. Fleming H L[J]. AIChE Symp Ser, 1988,84(261):19一27.
    [30] Kazutalca Takata, Kaxuyoshi Yamamoto, Rulin Bianc. Removal of humic substances with vibratory shear enhanced processing membrane filtration[J]. Water Supply:The Review Journal of the International Water Supply Association / Economic and Social Commission for Asia and the Pacific, United Nations, 0735-1917,1999, 17,(1):93-102
    [31] Cheryan M. Ultrafiltration Handbook[M]. Technomic Publishing Co, Lancaster,PA,1986.
    [32] 李书国. 超滤膜的污染原因及清洗方法[J]. 食品科学, 1999, 2: 28-30
    [33] 王晓琳, 杨健, 徐南平, 等. 液体膜分离技术研究与应用现状及其展望[J]. 膜科学与技术, 1999, 20(5): 41
    [34] Katsuyoshi Tanida, Kazutaka Takata, Satoru Komori. Scale-up law of vibrating membrance separation sepration system[J]. 化学工学论文集, 0386-216X, 2002 Vol.28,no.2p:143-149
    [35] Kazutalca Takata, Kaxuyoshi Yamamoto, Rulin Bianc. Removal of humic substances with vibratory shear enhanced processing membrane filtration. Water Supply[J]. The Review Journal of the International Water Supply Association / Economic and Social Commission for Asia and the Pacific, United Nations, 0735-1917, 1999, 17(1): 93-102.
    [36] Brad Culkin, Ann Plotkin, Michele Monroe. Solve Membrane Fouling Problems with High-Shear Filtration[J]. Chemical Engineering Progress, 1998, 94(1): 29-33
    [37] 赵福雄, 徐谋华. 酵母振动膜过滤系统的应用研究[J]. 现代食品科技, 2005, 21 (2):84
    [38] Jaffrin, MY Ding, LH; Akoum, O Brou, A. Aydrodynamic comparison between rotating disk and vibratory dynamic filtration systems[J]. Journal of Membrane Science, 0376-7388, 2004, 242 (2) :155-167
    [39] Petala, MD, Zouboulis, AI. Vibratory shear enhanced processing membrane filtration applied for the romoval of natural organic matter from surface waters[J]. Journal of Membrane Science, 2006 , 269 (1):1-14
    [40] Postlethwaite J, Lamping SR., Leach GC, Hurwitz MF, Lye GJ. Flux and transmission characteristics of a vibrating microfiltration system operated at high biomass loading[J]. Journal of Membrane Science, 0376-7388, 2004 , 228 (1):89-101
    [41] Brett Elias, Jabez Van Cleef. High-Shear Membrane separation for Process & Wastewater Treatment[J]. Chemical Engineering, 1998, 105(10):94-104
    [42] 楼永通. 膜分离技术在中药生产中的应用. 中国药学会学术年会.昆明. 2004,中国药学会学术年会论文集. 200407: 331-335
    [43] 周宏兵, 黄涛, 赖毅勤, 等. 超频振动膜过滤法在小叶榕叶水提物分离中的应用研究[J] . 食品与药品, 2007, 9(06A):11-14
    [44] 周宏兵, 黄涛, 赖毅勤, 等.小叶榕叶水提物超频振动膜过滤工艺的研究[J] .广东药学院学报, 2007, 23(2):116-118
    [45] 钟方晓. 金银花有效成分标准物质的研究[J]. 时珍国医国药,2004,15(7):394-395
    [46] 宋德花, 梁运霞, 刘广文, 等. 正交试验法优选金银花中绿原酸水提醇沉工艺的研究[J]. 黑龙江畜牧兽医职业学院学报,2006,5(1):21-24
    [47] 国家药典委员会.《中国药典》一部[s].2005:153
    [48] 倪永兴, 彭图婉, 曾诠.多指标试验全概率公试评分法研究槐米炭炮制工艺[J]. 中国药科大学学报,1995,26(6):259
    [49] 周怀悟,倪永兴. 医药应用慨率统计[M]. 上海:百家出版社,1990.
    [50]白雪梅,罗强,贾天军, 等. 金银花 HPLC 指纹图谱的研究[J]. 中成药, 2004,26(7): 521-524
    [51] ANDREW LIVINGSTON, LUDMILA PEEVA. Membrane Separation in Green Chemical Processing[J]. Solvent Nanofiltration in Liquid Phase Organic Synthesis Reactions, Ann. N.Y. Acad.Sci., 2003,984:123- 141.
    [52] 田智勇,许启泰. 中药栀子的研究进展[J]. 时珍国医国药, 2004, 15(11):782-784
    [53] 乔 丹,薄显辉. 栀子药材提取工艺的优选[J]. 黑龙江医药, 2002,15(4):269-270
    [54] 国家药典委员会, 中华人民共和国药典一部[s]. 2005:173.
    [55] 楼永通.膜分离技术在中药生产中的应用. 中国药学会学术年会,昆明:2004年中国药学会学术年会论文集: 331-335
    [56] 周宏兵. 超频振动膜过滤系统在中药分离浓缩中的应用探讨. 全国中药标准研究学术研讨会. 广东珠海: 全国中药标准研究学术研讨会论文集. 200510: 311-314
    [57] Petala, MD, Zouboulis, AI. Vibratory shear enhanced processing membranefiltration applied for the removal of natural organic matter from surface waters[J]. Journal of Membrane Science, 2006, 269 (1):2-14
    [58] Kazutalca Takata, Kaxuyoshi Yamamoto, Rulin Bianc. Removal of humic substances with vibratory shear enhanced processing membrane filtration[J]. Water Supply, 1999,17 (1):93-102
    [59] 李淑莉,陈 斌.药液种类和浓度对超滤影响的初步研究[J].期膜科学与技术,1999,19(3):41-42
    [60] 任建新. 膜分离技术及其应用[M]. 北京:化学工业出版社,2003.
    [61] 吴 密, 于群主编. 现代制药企业成本核算与财务管理实务全书[M]. 吉林出版社: 2004 年
    [62] 张素萍主编. 中药制药工艺与设备[M]. 化学工业出版社:2005 年 10 月
    [63] 夏循礼, 陈 勇. 醇提水沉与水提醇沉提取杜仲叶活性成分的比较研究[J]. 湖北大学学报(自然科学版), 2003,03:48-51
    [64] 何兴. 现代制药企业可持续发展战略全书[M]. 中国科技出版社:2005 年.

© 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