川产道地药材白芷香豆素的分离、质量控制及透皮特性研究
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摘要
川产道地药材白芷(Angelica dahurica(Fisch.ex Hoffm.)Benth.etHook.f.var.formosana(Boiss.)Shan et Yuan.)具有散风除湿,通窍止痛,消肿排脓的功效,临床上主要用于各种疼痛。本文主要针对川产道地药材白芷治疗偏头痛的香豆素有效部位进行分离研究,在此基础上进行了川白芷香豆素有效部位的质量评价及透皮特性研究。
以总香豆素含量为评价指标,对香豆素有效部位的提取、分离纯化工艺进行了全面系统的研究,采用单因素考察和正交试验对其影响因素进行了筛选,确定了最佳工艺参数,进行了中试放大试验,10批川白芷香豆素有效部位样品中总香豆素含量均大于55%,结果表明该工艺重现性较好,适合大生产。
通过体内药效学试验确认川白芷香豆素有效部位对偏头痛具有明显影响后,采用硅胶柱层析法分离有效成分,得到了7个单一化合物,采用熔点测定、HPLC、TLC等方法,对其中2个化合物进行了纯度检查,同时采用~1H-NMR、~(13)C-NMR、MS对其余5个化合物进行了结构鉴定,为揭示川产道地药材白芷治疗偏头痛的物质基础提供了佐证。
为了保证川产道地药材白芷香豆素有效部位质量稳定、可控,对川白芷香豆素有效部位进行了质量评价体系研究,内容包括:一般检查项目、薄层色谱鉴别、含量测定研究(总香豆素、欧前胡素)等,并首次进行了川白芷香豆素有效部位的RP-HPLC指纹图谱研究。
首次采用改良的Franz扩散池对川产道地药材白芷香豆素有效部位进行了体外透皮特性研究,为了提高药物的经皮渗透量,对几种常用的促渗剂进行了筛选,结果表明川白芷香豆素有效部位本身的透皮速率J值为4.1350μg/cm~2·h左右,加入氮酮、油酸和冰片均具有提高其皮肤渗透性的作用,以浓度为2%的冰片促渗作用最强,使其透皮速率J值增加为26.905μg/cm~2·h左右。实验结果可为开发安全有效、质量稳定可控的川白芷香豆素透皮给药制剂奠定基础。
Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana (Boiss.) Shan et Yuan is a genuine staple herb of Sichuan,has the function of dispel Wind and remove Dampness,dredge the orifices to relieve pain,subdue swelling and evacuate of pus.It is ofen used to cure all kinds of pain.In this reaserch,the seperation process of active components in Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook. f.var.formosana(Boiss.) Shan et Yuan of treating hemicrania is studied. After that the quality standard and outside-body transdermal characteristics of the effective extraction products was researched.
First,content of coumarin was chosen as indexe,single factor and orthogonal design were used in selecting the optimum extract and separate conditions.After the best technologic parameter was ascertained,pilot experiment was finished.Under the best condition,10 batches of extraction products were made.The content of coumarin in extraction products can be above 55%.It is proved that the technique of preparation was reasonable and practical.
Pharmacodynamic experiment was used to identify the extraction products is active for curing hemicrania.Then the active compound was separated by the sillaca gel chromatography.7 constituens were separated from the active extraction products.The degree of purity in two of those constituents were identified by HPLC、TLC、determination of melting point.The structures of 5 constituens else were confirmed by ~1H-NMR、~(13)C-NMR、MS.The above reseach can offer evidence for the active components of Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f. var.formosana(Boiss.)Shan et Yuan in treating hemicrania.
In order to make sure that active extraction products is contronllable, stable,research on quality standard of active extraction products was carried out.The research was as follows:the general items,TLC to identify active extraction products,UV-VIS and HPLC to determine the content of coumarin and imperatorin.RP-HPLC fingerprint for quality assessment of extraction products from Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana(Boiss.) Shan et Yuan is the first time to reaserch..
Improved Franz diffuse pool adopted to study the outside-body transdermal characteristics of active extraction products from Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana(Boiss.) Shan et Yuan the first time.For the purpose of improving the transdermal pervasion quantity of the drug,several common permeation promoters were filtered,and the experimental results indicated that the coumarin of Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana (Boiss.) Shan et Yuan itself had good penetrability,whose transdermal velocity can reach about 4μg/cm~2·h.Adding permeation promoters as azone,oleic acid and borneol,can increase its penetrate velocity, especially 2%borneol.It can improve the penetrate velocity to about 26.905μg/cm~2·h.It can lay a foundation for reseach safe,effective, steadily and controllable transdermal delivery preperation.
以总香豆素含量为评价指标,对香豆素有效部位的提取、分离纯化工艺进行了全面系统的研究,采用单因素考察和正交试验对其影响因素进行了筛选,确定了最佳工艺参数,进行了中试放大试验,10批川白芷香豆素有效部位样品中总香豆素含量均大于55%,结果表明该工艺重现性较好,适合大生产。
通过体内药效学试验确认川白芷香豆素有效部位对偏头痛具有明显影响后,采用硅胶柱层析法分离有效成分,得到了7个单一化合物,采用熔点测定、HPLC、TLC等方法,对其中2个化合物进行了纯度检查,同时采用~1H-NMR、~(13)C-NMR、MS对其余5个化合物进行了结构鉴定,为揭示川产道地药材白芷治疗偏头痛的物质基础提供了佐证。
为了保证川产道地药材白芷香豆素有效部位质量稳定、可控,对川白芷香豆素有效部位进行了质量评价体系研究,内容包括:一般检查项目、薄层色谱鉴别、含量测定研究(总香豆素、欧前胡素)等,并首次进行了川白芷香豆素有效部位的RP-HPLC指纹图谱研究。
首次采用改良的Franz扩散池对川产道地药材白芷香豆素有效部位进行了体外透皮特性研究,为了提高药物的经皮渗透量,对几种常用的促渗剂进行了筛选,结果表明川白芷香豆素有效部位本身的透皮速率J值为4.1350μg/cm~2·h左右,加入氮酮、油酸和冰片均具有提高其皮肤渗透性的作用,以浓度为2%的冰片促渗作用最强,使其透皮速率J值增加为26.905μg/cm~2·h左右。实验结果可为开发安全有效、质量稳定可控的川白芷香豆素透皮给药制剂奠定基础。
Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana (Boiss.) Shan et Yuan is a genuine staple herb of Sichuan,has the function of dispel Wind and remove Dampness,dredge the orifices to relieve pain,subdue swelling and evacuate of pus.It is ofen used to cure all kinds of pain.In this reaserch,the seperation process of active components in Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook. f.var.formosana(Boiss.) Shan et Yuan of treating hemicrania is studied. After that the quality standard and outside-body transdermal characteristics of the effective extraction products was researched.
First,content of coumarin was chosen as indexe,single factor and orthogonal design were used in selecting the optimum extract and separate conditions.After the best technologic parameter was ascertained,pilot experiment was finished.Under the best condition,10 batches of extraction products were made.The content of coumarin in extraction products can be above 55%.It is proved that the technique of preparation was reasonable and practical.
Pharmacodynamic experiment was used to identify the extraction products is active for curing hemicrania.Then the active compound was separated by the sillaca gel chromatography.7 constituens were separated from the active extraction products.The degree of purity in two of those constituents were identified by HPLC、TLC、determination of melting point.The structures of 5 constituens else were confirmed by ~1H-NMR、~(13)C-NMR、MS.The above reseach can offer evidence for the active components of Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f. var.formosana(Boiss.)Shan et Yuan in treating hemicrania.
In order to make sure that active extraction products is contronllable, stable,research on quality standard of active extraction products was carried out.The research was as follows:the general items,TLC to identify active extraction products,UV-VIS and HPLC to determine the content of coumarin and imperatorin.RP-HPLC fingerprint for quality assessment of extraction products from Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana(Boiss.) Shan et Yuan is the first time to reaserch..
Improved Franz diffuse pool adopted to study the outside-body transdermal characteristics of active extraction products from Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana(Boiss.) Shan et Yuan the first time.For the purpose of improving the transdermal pervasion quantity of the drug,several common permeation promoters were filtered,and the experimental results indicated that the coumarin of Angelica dahurica(Fisch.ex Hoffm.)Benth.et Hook.f.var.formosana (Boiss.) Shan et Yuan itself had good penetrability,whose transdermal velocity can reach about 4μg/cm~2·h.Adding permeation promoters as azone,oleic acid and borneol,can increase its penetrate velocity, especially 2%borneol.It can improve the penetrate velocity to about 26.905μg/cm~2·h.It can lay a foundation for reseach safe,effective, steadily and controllable transdermal delivery preperation.
引文
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[1]国家药典委员会.中华人民共和国药典.北京:化学工业出版社,2005
[2]野口敬身,河南实.伞型科植物の有效成分にする研究.药学杂志,1938,58(4):370
[3]秦清之.和白芷成分研究.药学杂志,1963,83(6):606
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[6]王梦月,贾敏如,马逾英,等.白芷镇痛有效部位的化学成分研究.中国药学杂志,2005,40(8):583-585
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