连翘挥发油不同馏分药效学及自乳化给药系统的研究
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摘要
连翘为木犀科植物连翘Forsythia suspensa(Thunb.)Vahl的干燥果实。味苦,无毒,性微寒。连翘作为中医常用的清热解毒药,历来被视为疮家要药。现代药理研究表明,连翘具有广谱抗菌、抗病毒、抗炎、解热、镇痛,止吐、利尿等作用。本实验主要针对其在抗炎、解热、镇痛方面的作用进行了一系列的研究。
首先采用水蒸气蒸馏法提取连翘油。通过试验发现该方法耗能小、工艺简单,提取的挥发油纯度高,容易进行下一步分离。
将连翘油提取出后,本试验选择了真空精馏法作为分段分离连翘油的方法。将连翘油按照不同的温度分段分离为7个组分,分别为30℃以下,30℃～40℃,40℃～60℃,60℃～85℃,85℃～95℃,95℃～120℃以及釜底残留物。结果表明真空精馏不但能将连翘挥发油中所含的成分分段分离,还可以把某些成分高度富集起来。
连翘油在真空精馏塔中分段分离后,进一步研究了不同温度段的组分的抗炎,消肿,解热,镇痛的药理作用,结果从不同组分中发现了不仅有抗炎、镇痛的成分,还具有致炎、致痛的成分,但是单个组分的药效不如连翘原油的药效强。.当去除掉其中致炎致痛组分后,将其他组分重新组合,发现比原挥发油抗炎,镇痛的效果更好。此试验表明了中药是一个协同作用的整体,连翘原油中多种组分同时作用于机体所产生的药效的强度超过各组分单独作用的总和。
由于连翘油具刺激性,并有强烈刺鼻的味道,直接口服病人将难以下咽,因此本文将分离重组后的连翘油制成一种实用新型的口服制剂—连翘油自乳化口服制剂,并最终制备成软胶囊,使其更便于服用。自乳化后的连翘油口服制剂的刺激性大大减小,毒副作用也大大降低,半数致死量从6.2ml/kg增加到9.9ml/kg.。说明了自乳化过程中可能由于乳滴包裹住了挥发性成分,使得其在体内缓慢释放,缓和了药物的毒副作用。
Forsythia is a dry fruit of Oleaceae Forsythia plants. It is bitter, non-toxic and slightly cold. Forsythia is clearing away heat and toxic drug commonly used in Chinese medicine,it has always been regarded as an important drug for the treatment of traumatic. Modern pharmacological Studies Show that Forsythia has functions of antibacterium, antivirus, anti-inflammation,antipyretic,analgesic diuresis etc. This experiment has carried on a series of research mainly aimed at its roles of anti-inflammatory, antipyretic and analgesia.
First we use steam distillation to forsythia extrac t forsythia oil. Through the experiment, we found that this method is simple, little energy consumption, extraction of oil is purity and it is easy to separate.
This experiment choses vacuum distillation method to separation of the oil. We have separated the oil into seven components according to the different temperature. They are 30℃degrees below, 30℃～40℃, 40℃～60℃, 60℃～85℃, 85℃～95℃, 95℃～120℃and residue. Results show that the vacuum distillation can ont only separate the ingredients of forsythia naphtha, but also some ingredients can be highly enriched.
We studied the pharmacological functions of anti-pyretic,anti-inflammatory, detumescence analgesic of the components for different temperature after Forsythia oil had been separated in the vacuum rectifying tower. Results shows that the different components have not only anti-inflammation and analgesic ingredient,but also have inflammatory and pain ingredient,and the efficacy of crude oil is better than single forsythia components. When inflammatory and pain ingredient had been removed, We were re-combination of other components, then we find that the effect of Anti-inflammatory and analgesia are better than the original naphtha's,The experiment shows that the traditional Chinese medicine is a whole of synergy. Efficacy of many components of crude oil produced in the body is better than the sum of function components separately.
Because forsythia oil has excitant and strong pungent flavor,patients will be difficult to swallow if we are direct oral. Therefore this paper put the forsythia oil after have been separated and recombined into a new products—Forsythia oil SEDDS, eventually we made it soft capsule and make it easier for use. Irritating and side effects of Forsythia oil SEDDS are reduced greatly.LD50 increased from the 4.95 ml/kg to 7ml/kg . This phenomenon describes the volatile components may be surroundded by milk drops in n the process of SEDDS, It slow releases in the body and reduces the side effects of drugs.
首先采用水蒸气蒸馏法提取连翘油。通过试验发现该方法耗能小、工艺简单,提取的挥发油纯度高,容易进行下一步分离。
将连翘油提取出后,本试验选择了真空精馏法作为分段分离连翘油的方法。将连翘油按照不同的温度分段分离为7个组分,分别为30℃以下,30℃～40℃,40℃～60℃,60℃～85℃,85℃～95℃,95℃～120℃以及釜底残留物。结果表明真空精馏不但能将连翘挥发油中所含的成分分段分离,还可以把某些成分高度富集起来。
连翘油在真空精馏塔中分段分离后,进一步研究了不同温度段的组分的抗炎,消肿,解热,镇痛的药理作用,结果从不同组分中发现了不仅有抗炎、镇痛的成分,还具有致炎、致痛的成分,但是单个组分的药效不如连翘原油的药效强。.当去除掉其中致炎致痛组分后,将其他组分重新组合,发现比原挥发油抗炎,镇痛的效果更好。此试验表明了中药是一个协同作用的整体,连翘原油中多种组分同时作用于机体所产生的药效的强度超过各组分单独作用的总和。
由于连翘油具刺激性,并有强烈刺鼻的味道,直接口服病人将难以下咽,因此本文将分离重组后的连翘油制成一种实用新型的口服制剂—连翘油自乳化口服制剂,并最终制备成软胶囊,使其更便于服用。自乳化后的连翘油口服制剂的刺激性大大减小,毒副作用也大大降低,半数致死量从6.2ml/kg增加到9.9ml/kg.。说明了自乳化过程中可能由于乳滴包裹住了挥发性成分,使得其在体内缓慢释放,缓和了药物的毒副作用。
Forsythia is a dry fruit of Oleaceae Forsythia plants. It is bitter, non-toxic and slightly cold. Forsythia is clearing away heat and toxic drug commonly used in Chinese medicine,it has always been regarded as an important drug for the treatment of traumatic. Modern pharmacological Studies Show that Forsythia has functions of antibacterium, antivirus, anti-inflammation,antipyretic,analgesic diuresis etc. This experiment has carried on a series of research mainly aimed at its roles of anti-inflammatory, antipyretic and analgesia.
First we use steam distillation to forsythia extrac t forsythia oil. Through the experiment, we found that this method is simple, little energy consumption, extraction of oil is purity and it is easy to separate.
This experiment choses vacuum distillation method to separation of the oil. We have separated the oil into seven components according to the different temperature. They are 30℃degrees below, 30℃～40℃, 40℃～60℃, 60℃～85℃, 85℃～95℃, 95℃～120℃and residue. Results show that the vacuum distillation can ont only separate the ingredients of forsythia naphtha, but also some ingredients can be highly enriched.
We studied the pharmacological functions of anti-pyretic,anti-inflammatory, detumescence analgesic of the components for different temperature after Forsythia oil had been separated in the vacuum rectifying tower. Results shows that the different components have not only anti-inflammation and analgesic ingredient,but also have inflammatory and pain ingredient,and the efficacy of crude oil is better than single forsythia components. When inflammatory and pain ingredient had been removed, We were re-combination of other components, then we find that the effect of Anti-inflammatory and analgesia are better than the original naphtha's,The experiment shows that the traditional Chinese medicine is a whole of synergy. Efficacy of many components of crude oil produced in the body is better than the sum of function components separately.
Because forsythia oil has excitant and strong pungent flavor,patients will be difficult to swallow if we are direct oral. Therefore this paper put the forsythia oil after have been separated and recombined into a new products—Forsythia oil SEDDS, eventually we made it soft capsule and make it easier for use. Irritating and side effects of Forsythia oil SEDDS are reduced greatly.LD50 increased from the 4.95 ml/kg to 7ml/kg . This phenomenon describes the volatile components may be surroundded by milk drops in n the process of SEDDS, It slow releases in the body and reduces the side effects of drugs.
引文
[1]李倩,冯卫生.连翘的化学成分研究进展.河南中医学院学报,2005,20(117):26-28
[2]张海燕,连翘化学成分及药理活性的研究进展[J].中药材,2000,23(10):657
[3]芮菁,尾崎幸,唐元泰.连翘提取物的抗炎镇痛作用.中草药,1999,30(1):43
[4]张其兰,赵鲁明,滕伯刚.牙痛灵镇痛、抗炎及抑菌作用的研究.中成药,1994,16(8):35
[5]刘悦,宋少江,徐绥绪等.连翘化学成分研究[J].沈阳药科大学学报,2003,2(25-27)
[6]刘明,中药连翘药理作用的研究近况.现代医药卫生,2007,23(16):2438-2439
[7]全健,超临界流体萃取技术在提取中药挥发油中的应用.广东微量元素科学,2001,8(7):13-16
[8]应安国,许松林,徐世民.间歇真空精馏提纯桉叶油的研究.林产工业,2005,32(2):29-31
[9]许松林,应安国,王淑华.真空精馏提纯桃醛的研究.精细石油化工,2004,6:43-45
[10 杨兆娟,周荣.从山苍籽油中提取高纯柠檬醛.香料香精化妆品,2002,4:13-15
[11]R.Neslihan Gursoy.Simon Benita.Self-emulsifying drug delivery sys-tems(SEDDS) for improved oral delivery of lipophilic drugs.Biomedecine & Pharmacotherapy,2004,58(3):173-182
[12]Siew PY,Kah HY.Influence of lipolysis and droplet size on tocotrienol absorption from self-emulsifying formulations.Int J of Pharm,2004,281:67-78
[13]J.You,FD.Cui,QRLi,et al.A novel formulation design about water-insoluble oily drug:preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits.Int J Pharm,2005,288:315-323
[14]S.Nazzal,Smalyukh,OD.Lavrentovich,et al.Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system(SNEDDS) of ubiquinone:mechanism and progress of emulsion formation.Int J Pharm,2002,235(1-2):247-265
[15]Attama,Nzekwea,Nnamania,et al.The use of solid self-emulsifying systems in the delivery of diclofenac.Int J Pharm,2003,262:23-28
[16]李军,孙兰义,崔铭伟.隔壁精馏塔技术进展.化工进展,2007,26:20-22
[17]吴济民;李识寒;于健等.新型填料塔技术在环己烯-环己烷萃取精馏塔中的应用.化工进展,2004,23(8):880-882
[18]陈昀,刘红茹.计算精馏塔理论塔板数新方法的开发.计算机与应用化学,2007,24(5):681-684
[19]肖会敏,王四旺,王剑波等.连翘挥发油的成分分析以及药理作用的研究进展.时珍国医国药,2008,19(8):20447-2048
[20 曾南,药理与中药药理实验.北京,科学出版社,2008
[21]李莉,王中彦,莫凤奎.自乳化药物传递系统的研究概况.药学专论,2005,14(2):25-27
[22]周庆辉,平其能.自乳化药物传递系统的应用与前景,药学进展,2001,25(3):134-138
[23]Pouron,CW.Formulation of self-emulsifying drug delivery system[J].Adv Drug Deliv Rev,1997,235:47-58
[24]贾伟,高文远,邱明丰等.药物控释新剂型[M].北京:化学工业出版社,2005
[25]川龙晓英,杨帆,李丽等.水飞蓟素自乳化给药系统处方设计及溶出度评价[J].中国药师,2004,7(7):496-498.
[26]李国栋,高申,张勇等.月见草油自乳化制剂处方研究[J].第二军医大学学报,2004,25(3):320-322
[27]凌桂霞,孙进,殷静等.桂利嗪自微乳化软胶囊的制备和溶出度的考察[J].中国药学杂志,2005,40(19):1482-1484
[28]李娟,张燕,王广基.茵拉西坦自乳化给药系统与片剂的药代动力学及体内外相关性的研究(英文).中国临床药理学与治疗学,2007,12(4):434-439
[29]刁雨辉,全新勇,周建平.尼索地平自微乳制剂稳定性的影响因素.中国医院药学杂志,2007,27(2):215-218
[2]张海燕,连翘化学成分及药理活性的研究进展[J].中药材,2000,23(10):657
[3]芮菁,尾崎幸,唐元泰.连翘提取物的抗炎镇痛作用.中草药,1999,30(1):43
[4]张其兰,赵鲁明,滕伯刚.牙痛灵镇痛、抗炎及抑菌作用的研究.中成药,1994,16(8):35
[5]刘悦,宋少江,徐绥绪等.连翘化学成分研究[J].沈阳药科大学学报,2003,2(25-27)
[6]刘明,中药连翘药理作用的研究近况.现代医药卫生,2007,23(16):2438-2439
[7]全健,超临界流体萃取技术在提取中药挥发油中的应用.广东微量元素科学,2001,8(7):13-16
[8]应安国,许松林,徐世民.间歇真空精馏提纯桉叶油的研究.林产工业,2005,32(2):29-31
[9]许松林,应安国,王淑华.真空精馏提纯桃醛的研究.精细石油化工,2004,6:43-45
[10 杨兆娟,周荣.从山苍籽油中提取高纯柠檬醛.香料香精化妆品,2002,4:13-15
[11]R.Neslihan Gursoy.Simon Benita.Self-emulsifying drug delivery sys-tems(SEDDS) for improved oral delivery of lipophilic drugs.Biomedecine & Pharmacotherapy,2004,58(3):173-182
[12]Siew PY,Kah HY.Influence of lipolysis and droplet size on tocotrienol absorption from self-emulsifying formulations.Int J of Pharm,2004,281:67-78
[13]J.You,FD.Cui,QRLi,et al.A novel formulation design about water-insoluble oily drug:preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits.Int J Pharm,2005,288:315-323
[14]S.Nazzal,Smalyukh,OD.Lavrentovich,et al.Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system(SNEDDS) of ubiquinone:mechanism and progress of emulsion formation.Int J Pharm,2002,235(1-2):247-265
[15]Attama,Nzekwea,Nnamania,et al.The use of solid self-emulsifying systems in the delivery of diclofenac.Int J Pharm,2003,262:23-28
[16]李军,孙兰义,崔铭伟.隔壁精馏塔技术进展.化工进展,2007,26:20-22
[17]吴济民;李识寒;于健等.新型填料塔技术在环己烯-环己烷萃取精馏塔中的应用.化工进展,2004,23(8):880-882
[18]陈昀,刘红茹.计算精馏塔理论塔板数新方法的开发.计算机与应用化学,2007,24(5):681-684
[19]肖会敏,王四旺,王剑波等.连翘挥发油的成分分析以及药理作用的研究进展.时珍国医国药,2008,19(8):20447-2048
[20 曾南,药理与中药药理实验.北京,科学出版社,2008
[21]李莉,王中彦,莫凤奎.自乳化药物传递系统的研究概况.药学专论,2005,14(2):25-27
[22]周庆辉,平其能.自乳化药物传递系统的应用与前景,药学进展,2001,25(3):134-138
[23]Pouron,CW.Formulation of self-emulsifying drug delivery system[J].Adv Drug Deliv Rev,1997,235:47-58
[24]贾伟,高文远,邱明丰等.药物控释新剂型[M].北京:化学工业出版社,2005
[25]川龙晓英,杨帆,李丽等.水飞蓟素自乳化给药系统处方设计及溶出度评价[J].中国药师,2004,7(7):496-498.
[26]李国栋,高申,张勇等.月见草油自乳化制剂处方研究[J].第二军医大学学报,2004,25(3):320-322
[27]凌桂霞,孙进,殷静等.桂利嗪自微乳化软胶囊的制备和溶出度的考察[J].中国药学杂志,2005,40(19):1482-1484
[28]李娟,张燕,王广基.茵拉西坦自乳化给药系统与片剂的药代动力学及体内外相关性的研究(英文).中国临床药理学与治疗学,2007,12(4):434-439
[29]刁雨辉,全新勇,周建平.尼索地平自微乳制剂稳定性的影响因素.中国医院药学杂志,2007,27(2):215-218