祛风凉血脂质体软膏的制备工艺及质量标准研究
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摘要
祛风凉血脂质体软膏处方由紫草、补骨脂、红花、蒺藜、川芎等八味中药组成,是临床经验方,以祛风润燥、活血通络为治疗原则,是用于治疗祛风凉血的纯中药现代外用制剂。本课题通过查阅大量的国内外文献资料和综述,设计并实施了对原料药材的提取工艺、脂质体软膏的成型工艺、制剂质量标准及制剂的稳定性研究。
根据组方中每一味药材的理化性质、生物活性成分及中医药理论临床应用等特性,制定出用乙醇回流提取的制备工艺。通过单因素试验对浸泡时间进行了考察,通过正交试验,对提取时间、加乙醇量和提取次数、乙醇浓度进行了考察,并确定其最佳提取工艺参数条件;同时对脂质体软膏制剂的成型工艺及中试等都进行了全面系统的研究,建立了科学合理的工艺技术路线。
为确保制剂的质量可控,充分利用现代分析手段对祛风凉血脂质体软膏的质量标准进行了研究。利用薄层色谱法(TLC)对制剂中补骨脂、川芎、当归等八味药材全部进行TLC鉴别;高效液相色谱法(HPLC)测定了君药补骨脂的有效成分补骨脂素和异补骨脂素的含量,并进行方法学考察。全面建立起了祛风凉血脂质体软膏的质量标准体系。
最后,通过留样观察法对制剂进行了为期0月、1个月、2个月、3个月、6个月的稳定性考察(还将继续),定期对制剂的性状、鉴别、含量测定等各方面检测,结果表明各考察指标无显著性差异,均符合标准及药典等各方面的规定,稳定性良好。
Qufeng Liangxue liposome cream is composed of eight Chinese medicinal herbs,which is an effective prescription to cure Qufeng Liangxue.It has the functions of Qufeng dampness、promoting the emergency of liver and kidney and activating blood circulation and dissipating blood stasis.The main topics of medicinal raw materials extraction process,liposomes ointment forming process,quality standards and the stability of formulations were studied.
Most of the active substances in the prescription and theri pharmacologic action have been identified on the whole.Based on the former study results,the experiment extracted active substances according to their physical and chemical properties.Soaking time was studied singly.The potential influence factors to the performance of extraction were fully considered.The techniques of alcohol extract was designed in scientific and reasonable way with orthogonal design.The reasonable extract equipments and technique conditions were optimized by taking those representative effective constituents as citerion.Also,the process conditions of and formulation were studied before the processing parameters were determined.
In order to guarantee the quality and curative effects of Qufeng Liangxue liposome cream, quality standard its set up was with the help of modern science and technology,such as TLC and HPLC. After a series of experimental studies,the most important traditional Chinese medicine herb in the prescription was controled quantitatively,and the quality standards were established.
In addition,primary stability was tested in three lots of pilot study samples during the period of six months,and all the items covered the certification.
The experimental result suggested that the technology of Qufeng Liangxue liposome cream convenient and feasible,the physical and chemical properties stable and the quality controllable.
根据组方中每一味药材的理化性质、生物活性成分及中医药理论临床应用等特性,制定出用乙醇回流提取的制备工艺。通过单因素试验对浸泡时间进行了考察,通过正交试验,对提取时间、加乙醇量和提取次数、乙醇浓度进行了考察,并确定其最佳提取工艺参数条件;同时对脂质体软膏制剂的成型工艺及中试等都进行了全面系统的研究,建立了科学合理的工艺技术路线。
为确保制剂的质量可控,充分利用现代分析手段对祛风凉血脂质体软膏的质量标准进行了研究。利用薄层色谱法(TLC)对制剂中补骨脂、川芎、当归等八味药材全部进行TLC鉴别;高效液相色谱法(HPLC)测定了君药补骨脂的有效成分补骨脂素和异补骨脂素的含量,并进行方法学考察。全面建立起了祛风凉血脂质体软膏的质量标准体系。
最后,通过留样观察法对制剂进行了为期0月、1个月、2个月、3个月、6个月的稳定性考察(还将继续),定期对制剂的性状、鉴别、含量测定等各方面检测,结果表明各考察指标无显著性差异,均符合标准及药典等各方面的规定,稳定性良好。
Qufeng Liangxue liposome cream is composed of eight Chinese medicinal herbs,which is an effective prescription to cure Qufeng Liangxue.It has the functions of Qufeng dampness、promoting the emergency of liver and kidney and activating blood circulation and dissipating blood stasis.The main topics of medicinal raw materials extraction process,liposomes ointment forming process,quality standards and the stability of formulations were studied.
Most of the active substances in the prescription and theri pharmacologic action have been identified on the whole.Based on the former study results,the experiment extracted active substances according to their physical and chemical properties.Soaking time was studied singly.The potential influence factors to the performance of extraction were fully considered.The techniques of alcohol extract was designed in scientific and reasonable way with orthogonal design.The reasonable extract equipments and technique conditions were optimized by taking those representative effective constituents as citerion.Also,the process conditions of and formulation were studied before the processing parameters were determined.
In order to guarantee the quality and curative effects of Qufeng Liangxue liposome cream, quality standard its set up was with the help of modern science and technology,such as TLC and HPLC. After a series of experimental studies,the most important traditional Chinese medicine herb in the prescription was controled quantitatively,and the quality standards were established.
In addition,primary stability was tested in three lots of pilot study samples during the period of six months,and all the items covered the certification.
The experimental result suggested that the technology of Qufeng Liangxue liposome cream convenient and feasible,the physical and chemical properties stable and the quality controllable.
引文
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[26]陈文梅,金鸣,吴伟等,视食品红花黄色素抗血小板激活银子作用的研究[J].心肺血管杂志,2001,20(14):201,240.
[27]夏玉叶,盛雨辰,羟基红色素A对大鼠血栓形成和血小板聚集功能的影响[J].中国药理学通报,2005,21(11):1400-1401.
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[31]Liu J,Chen H S,Xu Y X,et all Studies on chemical cons2 tituents of Tribu lus terrestris L 1[J]1 Acad J Second M ilM edU niv(第二军医大学学报),2003,24(2):221-222.
[32]Li J X,Shi Q,Xiong Q B,et al.Tribulasam ides A and B,new hepatopo ro tective lignanam ides from frutis of T ribulusterrestris:indication of cytopro tectiveactivity in murine heap-tocyte culture[J]Planta M ed,1998,64:628-6311
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[34]Chen H S,Chen Q J,Xuan W D.A new organic acid from Tribulus terrestris[J]A cad J Second Miled Univ(第二军医大学学报),2004,25(11):1241-1242.
[35]Huang X L,Zhang Y S,Liang Z Y.Studies on water so lublepo lysaccharides isolated from T ribulus terrestris-purification and prelim inary structural determination of heteropo ly-saccaride H[J].Acta Pham Sin(药学学报),1991,26(8):578-583.
[36]De KockWT,Enslin P R,Chemical investigation of photosensitization diseases of domestric animals Ii Isolation and characterization of steroidal sapogenins from T ribu lus terrestris[J].Afr Chem Inst,1958,11:33-36.
[37]杨柳,赖海生,蔡红兵。白蒺藜对酪氨酸酶活性的双向调节作用[J].陕西中医,2005,26 (4):370-573
[38]邓燕,杨柳,安胜利,不同浓度中药刺蒺藜对黑色素细胞和酪氨酸酶的作用[J].上海第一军医大学学报,2002,22(11):1017-1019.
[39]方欢乐,陈衍斌,何首乌的研究进展[J].现代中医药,2006,26(6):60-61.
[40]杨晓笛,卢锋等.中药紫草有效成分的提取[J].汕头大学学报,2002,17(4):67-69.
[41]李晓瑾,谭秀芳,马媛,等.药用植物紫草的研究进展[J].新疆师范大学学2005,24(4):69-71.
[42]谢秀琼.对制剂中紫草相关成分和提取工艺探讨[J].中国药房,1997,8(2):25.
[43]应静芝.紫草在儿科临床应用举隅[J].浙江临床医学2002.10(4):729.
[44]孙培杰.紫草的要离作用与临床应用研究进展[J].中医药信息 2002.19(4):19.
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[2]徐小柯.祛风凉血的发病机制研究进展[J].国外医学皮肤性病学分册,1995,21,4:204
[3]李宗华.祛风凉血的治疗进展[J],Mod Diagn treat现代诊疗与治疗,2007,Mar18(2).
[4]韩玲,祛风凉血及中医药治疗研究进展.中药药理与临床,2006,22(6):77-80.
[5]屈岚,薛长连,李成建.中医药治疗祛风凉血研究探要[J]中医药学刊,2004,22(3):529-531.
[6]刘瓦利.祛风凉血的中医辨证与治疗[J].中国临床医生,2005,33(2):50-52.
[7]徐建国.补骨脂对酪氨酸酶激活作用[J].中草药,1991,22(4):168-169.
[8]郭秀芝,刘卫萍,杨杰.补骨脂的药理活性及其开发利用[J].中医药学报,2005,33(5)34-35
[9]王淑云.补骨脂的药理作用研究[J].时针国医国药,2006,17(6)1801-1802
[10]M kaoudji,FDe Pachtere,CPouget,et al.ThereAdditional Phthalide Derivatives and Two Dimers,From ligusticam waclichiii rhizomes[J].Nat Prod,1986,49(5):872.
[11]M kobayashi and HMitsyhashi.Studies on the constituents of Umbellifera Plants ⅩⅦ.Structure of Three New ligustilide Deriva-tives from ligusticam wallichiii.ChemPharm Ball,1987,35(12):4789.
[12]钟凤林,杨连菊,吉力等.对不同产地和品种川芎中挥发油的研究[J].中国中药杂志.
[13]王文祥,顾明,蒋小岗等,川芎成分的化学研究[J].中草药,2002,33(1):4-5.
[14]杨丽红,谢秀琼,万丽,川芎化学成分研究[J].时珍国医国药,2007,33(7):6751-6752.
[15]梁日欣,廖福龙,韩东.川芎预处理对麻醉家兔心肌缺血再灌注损伤的保护[J].中药药理与临床,2000,16(2):11.
[16]左保华,周志冰,杨会杰,川芎嗪对再灌注心率失常的预防作用[J]九江医学,1995,10(4)196-198.
[17]蔡年英,Gwen Barer,川芎嗪对缺氧大鼠和雪貂肺血管的署长作用[J].中国应用生理学杂志,1990,6(1):19.
[18]李秋怡,干国平,刘焱文,川芎的化学成分及药理研究进展[J].时珍国医国药,2006,17(7)8921
[19]徐理纳,徐德成,张向嘉等.阿魏酸钠抗血小板聚集作用的机理研究-对TXA_2/PGI_2平衡的影响[J].中国医学科学院报,1984,6(6):414
[20]陈飞,姚成.当归化学成分及其药理作用研究进展[J].中医药研究,2002,18(3):51-53.
[21]唐军,当归化学成分及其药理作用研究进展[J].中医中药,2005,23(2):120.
[22]钟小明,陈旭东,余鸿.当归药理作用研究进展[J].四川解剖学杂志,2007,15(1):44-46.
[23]朱惠京,张红英,吴光等.防风正丁醇萃取物对大鼠血液流变学的影响[J].中草药,1998,27(12):812.
[24]吴祯久,防风的抗凝作用实验研究[J].延边医学院学报,1994,17(1):16.
[25]李文,李丽,是元艳防风有效部位的药理作用研究[J]中医中药,2005,23(2):120.
[26]陈文梅,金鸣,吴伟等,视食品红花黄色素抗血小板激活银子作用的研究[J].心肺血管杂志,2001,20(14):201,240.
[27]夏玉叶,盛雨辰,羟基红色素A对大鼠血栓形成和血小板聚集功能的影响[J].中国药理学通报,2005,21(11):1400-1401.
[28]康丽,颜晓燕,辛志伟红花的药理作用研究进展[J].西南军医,2008,10(6):136-138.
[29]裴永娜,红花的药理作用和临床应用[J].时珍国医国药,2005,16(2):144-146
[30]孙国珍,张洁,马百平,蒺藜中甾体皂苷类化学成分研究进展[J].2007,38(7):1111-1114
[31]Liu J,Chen H S,Xu Y X,et all Studies on chemical cons2 tituents of Tribu lus terrestris L 1[J]1 Acad J Second M ilM edU niv(第二军医大学学报),2003,24(2):221-222.
[32]Li J X,Shi Q,Xiong Q B,et al.Tribulasam ides A and B,new hepatopo ro tective lignanam ides from frutis of T ribulusterrestris:indication of cytopro tectiveactivity in murine heap-tocyte culture[J]Planta M ed,1998,64:628-6311
[33]Wu T S,ShiL S,Kuo S C.A ikaloids and other constituents from T ribu lus terrestris [J].Phytochemistry,1999,50:1411-1415.
[34]Chen H S,Chen Q J,Xuan W D.A new organic acid from Tribulus terrestris[J]A cad J Second Miled Univ(第二军医大学学报),2004,25(11):1241-1242.
[35]Huang X L,Zhang Y S,Liang Z Y.Studies on water so lublepo lysaccharides isolated from T ribulus terrestris-purification and prelim inary structural determination of heteropo ly-saccaride H[J].Acta Pham Sin(药学学报),1991,26(8):578-583.
[36]De KockWT,Enslin P R,Chemical investigation of photosensitization diseases of domestric animals Ii Isolation and characterization of steroidal sapogenins from T ribu lus terrestris[J].Afr Chem Inst,1958,11:33-36.
[37]杨柳,赖海生,蔡红兵。白蒺藜对酪氨酸酶活性的双向调节作用[J].陕西中医,2005,26 (4):370-573
[38]邓燕,杨柳,安胜利,不同浓度中药刺蒺藜对黑色素细胞和酪氨酸酶的作用[J].上海第一军医大学学报,2002,22(11):1017-1019.
[39]方欢乐,陈衍斌,何首乌的研究进展[J].现代中医药,2006,26(6):60-61.
[40]杨晓笛,卢锋等.中药紫草有效成分的提取[J].汕头大学学报,2002,17(4):67-69.
[41]李晓瑾,谭秀芳,马媛,等.药用植物紫草的研究进展[J].新疆师范大学学2005,24(4):69-71.
[42]谢秀琼.对制剂中紫草相关成分和提取工艺探讨[J].中国药房,1997,8(2):25.
[43]应静芝.紫草在儿科临床应用举隅[J].浙江临床医学2002.10(4):729.
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