复方氨敏虎杖工艺研究
|
摘要
本文以复方氨敏虎杖胶囊为研究对象,通过工艺筛选和工艺优化,获得本制剂主要原料虎杖、千里光的提取工艺及胶囊生产的最佳处方和生产工艺。
首先,通过试验考察了中药虎杖和千里光的提取溶剂的浓度、溶剂量、提取时间、提取次数等对药物的影响,从而分析筛查出虎杖和千里光的最佳提取条件,制定出其提取工艺路线,生产出合格的复方氨敏虎杖胶囊的中药原料。
其次根据现有生产设备利用玻璃化温度原理对虎杖和千里光的喷雾干燥工序的工艺进行了优化,使干膏粉的质量和收率大大提高,有效降低了能源消耗和喷雾干燥时间,大大提高了干膏粉的出粉率。
再次,对复方氨敏虎杖硬胶囊的生产工艺进行了研究改进,通过改变辅料及辅料添加方法等手段,使本产品的生产工艺更具合理性和可操作性,使产品在保证质量的前提下既节约能耗又降低了生产成本,为今后大规模生产打下基础。
最后,进行稳定性考察,通过加速稳定性试验和含量变化分析,进一步验证复方氨敏虎杖胶囊研究中处方筛选和工艺优化的可靠性。
Compound Paracetamol and Chlorphenamine Maleate Capsules were studied in this paper. Through process screening and optimization, the extraction process of Polygonum cospidatum and climbing groundsel was obtained and the production technique and the formulation were founded.
First of all, the density, quantity, extraction time, extraction number of times of extraction resolver of Polygonum cospidatum and the climbing groundsel were inspected through the experiments. The best extraction conditions were obtained and the extraction process route and produced the qualified traditional Chinese medicine raw material of Compound Paracetamol and Chlorphenamine Maleate Capsule was formulated.
Secondly, under the existing equipment,utilizing glass temperature principle,the process of spray drying working procedure of Polygonum cospidatum and the climbing groundsel was optimized.The quality and yield of the dry powder have been improved greatly, the energy consumption and spray drying time have been reduced effectively,and producing powder rate of dry powder have been improved greatly.
Moreover, we made the research to improve the production processes of the compound made of two or more ingredients ammonia Polygonum cospidatum capsule.By changing the means of adjuvants and add method of adjuvants,we enriched the production technology with more rationality and effectiveness, making the products save energy consumption and reduce producing cost on the premise of ensuring the quality of products. All of this laid a foundation for producing on a large scale in the future.
Finally, we carried on the stable inspection.Through the acceleration stability test and the content change analysis,we further confirmed the reliability of prescription screening and the craft optimization which were applied in the research of the compound made of Compound Paracetamol and Chlorphenamine Maleate Capsule.
首先,通过试验考察了中药虎杖和千里光的提取溶剂的浓度、溶剂量、提取时间、提取次数等对药物的影响,从而分析筛查出虎杖和千里光的最佳提取条件,制定出其提取工艺路线,生产出合格的复方氨敏虎杖胶囊的中药原料。
其次根据现有生产设备利用玻璃化温度原理对虎杖和千里光的喷雾干燥工序的工艺进行了优化,使干膏粉的质量和收率大大提高,有效降低了能源消耗和喷雾干燥时间,大大提高了干膏粉的出粉率。
再次,对复方氨敏虎杖硬胶囊的生产工艺进行了研究改进,通过改变辅料及辅料添加方法等手段,使本产品的生产工艺更具合理性和可操作性,使产品在保证质量的前提下既节约能耗又降低了生产成本,为今后大规模生产打下基础。
最后,进行稳定性考察,通过加速稳定性试验和含量变化分析,进一步验证复方氨敏虎杖胶囊研究中处方筛选和工艺优化的可靠性。
Compound Paracetamol and Chlorphenamine Maleate Capsules were studied in this paper. Through process screening and optimization, the extraction process of Polygonum cospidatum and climbing groundsel was obtained and the production technique and the formulation were founded.
First of all, the density, quantity, extraction time, extraction number of times of extraction resolver of Polygonum cospidatum and the climbing groundsel were inspected through the experiments. The best extraction conditions were obtained and the extraction process route and produced the qualified traditional Chinese medicine raw material of Compound Paracetamol and Chlorphenamine Maleate Capsule was formulated.
Secondly, under the existing equipment,utilizing glass temperature principle,the process of spray drying working procedure of Polygonum cospidatum and the climbing groundsel was optimized.The quality and yield of the dry powder have been improved greatly, the energy consumption and spray drying time have been reduced effectively,and producing powder rate of dry powder have been improved greatly.
Moreover, we made the research to improve the production processes of the compound made of two or more ingredients ammonia Polygonum cospidatum capsule.By changing the means of adjuvants and add method of adjuvants,we enriched the production technology with more rationality and effectiveness, making the products save energy consumption and reduce producing cost on the premise of ensuring the quality of products. All of this laid a foundation for producing on a large scale in the future.
Finally, we carried on the stable inspection.Through the acceleration stability test and the content change analysis,we further confirmed the reliability of prescription screening and the craft optimization which were applied in the research of the compound made of Compound Paracetamol and Chlorphenamine Maleate Capsule.
引文
[1]浸出技术与中药制剂[J].中国药科大学药剂学教研室2009,11～13。
[2]徐荣周、廖立德、薛大权、夏洪林主编.药物制剂生产工艺与注解[M].北京.化学工业出版社.2008：21～30。
[3]王效山,王键等.制药工艺学[M].北京：北京科学技术出版社,2003.206-207。
[4]杜艳,浸出技术与中药制剂[J].山西：山西医大学报,2008.14～16。
[5]廖勇,药物制剂研究开发与生产新工艺技术应用大全[M].北京：当代中国音像出版社,2003.1043～1044。
[6]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：17-18
[7]毛永芬,窦夏睿.虎杖的性能特点及临床应用[J].河北中医,2003,25(8)：634-635.
[8]张建超,高新周,易德亮.虎杖中自藜芦醇苷提取分离工艺研究[J].时珍国医国药,2003,14(4)：257-258.
[9]全国中草药汇编编写组编.全国中草药汇编(上册)[M].北京：人民卫生出版社,1975：112～123.
[10]肖崇厚.中药提取鉴定原理[M].上海：上海科学技术出版社,1981,24～29.
[11]付昆.虎杖中自藜芦醇苷的提取分离及含量测定[J].中国现代中西医杂志,2003,1(9)：835-836.
[12]王丹,唐盈.中药虎杖中自藜芦醇甙含量测定的研究[J].中草药,1987,18(11)：16-18.
[13]林启寿.中草药成分化学[M].北京：科学技术出版社,1977,211～216.
[14]张喜云.虎杖的化学成分、药理作用与提取分离[J].天津药学,1999,11(8)：14-15.
[15]国家药典委员会.中华人民共和国药典[M].北京：化学工业出版社,2005.
[16]ZHANG Mian, WANG Lei, HUANG Lan, et al. Qualitative and quantitative analysis of rhizome of Polygonum cuspidatum[J]. Journal of Chinese Pharmaceutical Sciences.2004,13(2):106 111.
[17]Chu Qingcui, Peng Youyuan, Ye Jiannong. Determination ofactive ingredients of Polygonum cuspidatum Sied. et Zucc. by capillary electrophoresis with electrochemical detection[J]. ElectrOanalysis,2004,16(17):1434-1436.
[18]药物制剂研究开发与生产新工艺技术应用大全[M].北京.当代中国音像出版社,2003 1039
[19]浸出技术与中药制剂[J].中国药科大学药剂学教研室2009,11-13
[20]吴斌、吴立军.千里光属植物的化学成分研究进展[J].中国中药杂志,2003.28(2)：97
[21]李华、聂芳红、陈进东、等.千里光抗菌有效部位化学成分及其急性毒性研究[J].中兽医医药杂志.2008.1：7～8
[22]陈录新、李宁、张勉等、千里光的研究进展[J].海峡药学、2006.18(4)：13-14
[23]洪美玲.病理学[M].北京：人民卫生出版社.1999：49～50
[24]国家中医药管理局《中华本草》编委会.中华本草[M].上海：上海科技出版社.1999：1390。
[25]陈录新、马鸿雁、张勉等.千里光化学成分的研究[J].中国中药杂志.2006.31(22)：1872
[26]尚遂存、武雪芬、杨林莎.中草药食品抗氧化剂的筛选[J].天然产物研究与开发,1994.6(1)：36～38。
[27]梁爱华,叶祖光.千里光属植物的毒性研究进展[J].中国中药杂志,2006,3 1(2)：93-95.
[28]周杰,国兴明.贵州中药雪里见化学成分分离和纯化的初步研究[J].农业生物学报,2005,24(3)：265～266.
[29]唐栩,许东辉,梅雪婷,等.26种总黄酮类天然活性成分的药理研究进展[J].中药材,2003,26(1)：46.
[30]李德荣.千里光(菊科：千里光族)的核形态及其系统学意义[J].江西农业大学学报,2004,26(3)：399～400.
[31]张文平,张文书,曾雪英.千里光与甲氧苄氨嘧啶联用抗菌作用试验研究[J].江西医学检验,2004,22(6)：536～538.
[32]陈进军,王建华,耿果霞,等.千里光的化学成份鉴定及体外抗菌试验[J].动物医学进展,1999,20(4)：35-36.
[33]周艳娟,：李翠芹,王吉之.羽叶千里光不同部位提取物的抗氧化活性研究[J].现代生物医药研究进展,2008,8(3)：511-512.
[34]李华,聂芳红,陈进东,等.千里光抗菌有效部位化学成分及其急性毒性研究[J].中兽医药杂志,2008,1：7.
[35]汪劲松,潘继承.中草药千里光有效成分的提取及抑菌作用的研究[J].湖北师范学院学报(自然科学版),2000,3(20)：48～49.
[36]王效山,王键等.制药工艺学[M].北京：北京科学技术出版社,2003.253.
[37]君轩,玻璃化温度和脆性温度[J].世界橡胶工业,2005.6：52.
[38]张绪峤,药物制剂设备和车间工艺设计[M].中国医药科技出版社,2000：124～126.
[39]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：29-30
[40]徐荣周、廖立德、薛大权、夏洪林主编.药物制剂生产工艺与注解[M].北京.化学工业出版社.2008：629-630。
[41]Carstensen JT. Drug Stability (Principle and Practices). New York:Marcel Dekker Inc,1990.226-230.
[42]Murthy KS, et al. Ccurrent perspectives on the dissolution stability of solid oral dosage forms. J Pharm Sci,1993,82(2):112-113
[43]LuBIN,er al. Microencapsulation of Drugs. Ed. By Whateley TL. Harwood Academic Publishers. U.K.1992.103
[44]Chulia D,et al. Powder Technology and Pharmaceutical Processes, The Netherlands, Elsevier Science B. V.,1994.494-497
[45]Martindale The extra pharmacopoeia.28th Ed. London:The pharmaceutical press,1982.375,616,1070.
[46]卫生部药典委员会编.中国药典2005年版,二部附录,药物稳定性试验指导原则
[47]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：151-152.
[48]国家药品监督管理局.《药品生产质量管理规范》(1998年修订)
[49]韩瑞亭,药物制剂技术[M].中国农业大学出版社,2009：78-85.
[50]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：99-100
[51]卫生部药典委员会编.中国药典2005年版,二部附录,药物稳定性试验指导原则
[52]中国药典2005年版.二部.2005：附录176-179
[2]徐荣周、廖立德、薛大权、夏洪林主编.药物制剂生产工艺与注解[M].北京.化学工业出版社.2008：21～30。
[3]王效山,王键等.制药工艺学[M].北京：北京科学技术出版社,2003.206-207。
[4]杜艳,浸出技术与中药制剂[J].山西：山西医大学报,2008.14～16。
[5]廖勇,药物制剂研究开发与生产新工艺技术应用大全[M].北京：当代中国音像出版社,2003.1043～1044。
[6]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：17-18
[7]毛永芬,窦夏睿.虎杖的性能特点及临床应用[J].河北中医,2003,25(8)：634-635.
[8]张建超,高新周,易德亮.虎杖中自藜芦醇苷提取分离工艺研究[J].时珍国医国药,2003,14(4)：257-258.
[9]全国中草药汇编编写组编.全国中草药汇编(上册)[M].北京：人民卫生出版社,1975：112～123.
[10]肖崇厚.中药提取鉴定原理[M].上海：上海科学技术出版社,1981,24～29.
[11]付昆.虎杖中自藜芦醇苷的提取分离及含量测定[J].中国现代中西医杂志,2003,1(9)：835-836.
[12]王丹,唐盈.中药虎杖中自藜芦醇甙含量测定的研究[J].中草药,1987,18(11)：16-18.
[13]林启寿.中草药成分化学[M].北京：科学技术出版社,1977,211～216.
[14]张喜云.虎杖的化学成分、药理作用与提取分离[J].天津药学,1999,11(8)：14-15.
[15]国家药典委员会.中华人民共和国药典[M].北京：化学工业出版社,2005.
[16]ZHANG Mian, WANG Lei, HUANG Lan, et al. Qualitative and quantitative analysis of rhizome of Polygonum cuspidatum[J]. Journal of Chinese Pharmaceutical Sciences.2004,13(2):106 111.
[17]Chu Qingcui, Peng Youyuan, Ye Jiannong. Determination ofactive ingredients of Polygonum cuspidatum Sied. et Zucc. by capillary electrophoresis with electrochemical detection[J]. ElectrOanalysis,2004,16(17):1434-1436.
[18]药物制剂研究开发与生产新工艺技术应用大全[M].北京.当代中国音像出版社,2003 1039
[19]浸出技术与中药制剂[J].中国药科大学药剂学教研室2009,11-13
[20]吴斌、吴立军.千里光属植物的化学成分研究进展[J].中国中药杂志,2003.28(2)：97
[21]李华、聂芳红、陈进东、等.千里光抗菌有效部位化学成分及其急性毒性研究[J].中兽医医药杂志.2008.1：7～8
[22]陈录新、李宁、张勉等、千里光的研究进展[J].海峡药学、2006.18(4)：13-14
[23]洪美玲.病理学[M].北京：人民卫生出版社.1999：49～50
[24]国家中医药管理局《中华本草》编委会.中华本草[M].上海：上海科技出版社.1999：1390。
[25]陈录新、马鸿雁、张勉等.千里光化学成分的研究[J].中国中药杂志.2006.31(22)：1872
[26]尚遂存、武雪芬、杨林莎.中草药食品抗氧化剂的筛选[J].天然产物研究与开发,1994.6(1)：36～38。
[27]梁爱华,叶祖光.千里光属植物的毒性研究进展[J].中国中药杂志,2006,3 1(2)：93-95.
[28]周杰,国兴明.贵州中药雪里见化学成分分离和纯化的初步研究[J].农业生物学报,2005,24(3)：265～266.
[29]唐栩,许东辉,梅雪婷,等.26种总黄酮类天然活性成分的药理研究进展[J].中药材,2003,26(1)：46.
[30]李德荣.千里光(菊科：千里光族)的核形态及其系统学意义[J].江西农业大学学报,2004,26(3)：399～400.
[31]张文平,张文书,曾雪英.千里光与甲氧苄氨嘧啶联用抗菌作用试验研究[J].江西医学检验,2004,22(6)：536～538.
[32]陈进军,王建华,耿果霞,等.千里光的化学成份鉴定及体外抗菌试验[J].动物医学进展,1999,20(4)：35-36.
[33]周艳娟,：李翠芹,王吉之.羽叶千里光不同部位提取物的抗氧化活性研究[J].现代生物医药研究进展,2008,8(3)：511-512.
[34]李华,聂芳红,陈进东,等.千里光抗菌有效部位化学成分及其急性毒性研究[J].中兽医药杂志,2008,1：7.
[35]汪劲松,潘继承.中草药千里光有效成分的提取及抑菌作用的研究[J].湖北师范学院学报(自然科学版),2000,3(20)：48～49.
[36]王效山,王键等.制药工艺学[M].北京：北京科学技术出版社,2003.253.
[37]君轩,玻璃化温度和脆性温度[J].世界橡胶工业,2005.6：52.
[38]张绪峤,药物制剂设备和车间工艺设计[M].中国医药科技出版社,2000：124～126.
[39]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：29-30
[40]徐荣周、廖立德、薛大权、夏洪林主编.药物制剂生产工艺与注解[M].北京.化学工业出版社.2008：629-630。
[41]Carstensen JT. Drug Stability (Principle and Practices). New York:Marcel Dekker Inc,1990.226-230.
[42]Murthy KS, et al. Ccurrent perspectives on the dissolution stability of solid oral dosage forms. J Pharm Sci,1993,82(2):112-113
[43]LuBIN,er al. Microencapsulation of Drugs. Ed. By Whateley TL. Harwood Academic Publishers. U.K.1992.103
[44]Chulia D,et al. Powder Technology and Pharmaceutical Processes, The Netherlands, Elsevier Science B. V.,1994.494-497
[45]Martindale The extra pharmacopoeia.28th Ed. London:The pharmaceutical press,1982.375,616,1070.
[46]卫生部药典委员会编.中国药典2005年版,二部附录,药物稳定性试验指导原则
[47]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：151-152.
[48]国家药品监督管理局.《药品生产质量管理规范》(1998年修订)
[49]韩瑞亭,药物制剂技术[M].中国农业大学出版社,2009：78-85.
[50]毕殿周.药剂学(第四版)[M].人民卫生出版社,2002：99-100
[51]卫生部药典委员会编.中国药典2005年版,二部附录,药物稳定性试验指导原则
[52]中国药典2005年版.二部.2005：附录176-179