用于风湿病治疗的中药外用膏剂的应用现状及研究进展
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摘要
由于疗效确切、药性稳定、不良反应率低,用于风湿病治疗的中药外用膏剂越来越受到国内外学者的关注。本文选择经国家食品药品监督管理总局(CFDA)批准上市并用于治疗风湿病的中药外用膏剂为研究对象,对其剂型、品种以及规格等方面进行梳理与分析;查阅近年来发表的中药外用膏剂研究的相关文献,对其制剂新技术应用、制剂处方研究、成型工艺研究、药效学与安全性研究等进行归纳、分析和总结;指出用于风湿病治疗的中药外用膏剂研究中存在的问题,如缺乏新型制剂,相关促透剂的促透物质基础、促透机制、促透规律研究较少,质量控制标准研究中检测指标的选择不够全面,药代动力学的定性、定量研究相对匮乏等。同时,提出应规范中药外用膏剂的剂型分类及规格描述,亦应积极引进中药智能化、缓控释、靶向制剂等新剂型;加强相关促透剂本身透皮行为的研究,并探讨促透剂自身成分透皮吸收与促透皮吸收的相关性;采用生物效应指标或化学与生物效应相结合的综合评价指标,借鉴中药多维谱效学的最新研究成果,从而建立符合现代透皮理念的科学检测指标及质量控制方法。
Due to the definite curative effect,stable drug properties and low incidence of adverse reactions,the external traditional Chinese medicine( TCM) ointment for rheumatism treatment has attracted more and more attention from scholars at home and abroad. Based on the external TCM ointment for the treatment of rheumatism approved by China Food and Drug Administration( CFDA),this paper would comb and analyze their dosage forms,varieties,specifications,etc. On the other hand,this article summarizes the application of the new formulation technology,prescription research,study on the forming process,pharmacodynamics and safety research,etc. The problems existing in this area were pointed out, such as lack of new preparations; less research on the penetration material basis,the penetration enhancing mechanism,and the penetration enhancing law; the selection of detection indicators of quality control standards is not comprehensive enough; qualitative and quantitative studies of pharmacokinetics are relatively scarce and so on. Meanwhile, proper measures and suggestions are put forward. Not only the formulation classification and specification description of external TCM ointment should be standardized,but also new dosage forms such as intelligentized,controlled release and targeted preparations of Chinese medicine should be actively introduced; the study of transdermal activity of transdermal enhancer itself should be strengthened,and investigating the correlation between the transdermal absorption of the agent itself and promoting transdermal absorption; the biological effect index or indicators that combine chemical and biological effects should be used, and learning from the latest research achievements of multidimensional spectroscopy of Chinese herbal medicine,thereby establishing scientific detection indicators and quality control methods that conform to modern transdermal concept.
Due to the definite curative effect,stable drug properties and low incidence of adverse reactions,the external traditional Chinese medicine( TCM) ointment for rheumatism treatment has attracted more and more attention from scholars at home and abroad. Based on the external TCM ointment for the treatment of rheumatism approved by China Food and Drug Administration( CFDA),this paper would comb and analyze their dosage forms,varieties,specifications,etc. On the other hand,this article summarizes the application of the new formulation technology,prescription research,study on the forming process,pharmacodynamics and safety research,etc. The problems existing in this area were pointed out, such as lack of new preparations; less research on the penetration material basis,the penetration enhancing mechanism,and the penetration enhancing law; the selection of detection indicators of quality control standards is not comprehensive enough; qualitative and quantitative studies of pharmacokinetics are relatively scarce and so on. Meanwhile, proper measures and suggestions are put forward. Not only the formulation classification and specification description of external TCM ointment should be standardized,but also new dosage forms such as intelligentized,controlled release and targeted preparations of Chinese medicine should be actively introduced; the study of transdermal activity of transdermal enhancer itself should be strengthened,and investigating the correlation between the transdermal absorption of the agent itself and promoting transdermal absorption; the biological effect index or indicators that combine chemical and biological effects should be used, and learning from the latest research achievements of multidimensional spectroscopy of Chinese herbal medicine,thereby establishing scientific detection indicators and quality control methods that conform to modern transdermal concept.
引文
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[8]李学敏,王琼,兰颐,等.微乳技术对止痛凝胶膏剂中成分释放和含量变化的影响[J].中国中药杂志,2013,38(16):2614-2617.
[9]徐波,张来根,张农山,等.“MEMS微针促透‘易层’贴敷技术”治疗膝骨关节炎372例临床研究[J].时珍国医国药,2016,27(8):1912-1914.
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[11]赵立建,刘善新,苏酩,等.星点设计-效应面法优选活血巴布膏成型工艺[J].中国实验方剂学杂志,2016,22(13):19-22.
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[14]黄晓晨,宿树兰,钱大玮,等.不同促渗剂对少腹逐瘀方外用贴剂中效应成分群体外透皮吸收的影响[J].中草药,2014,45(21):3074-3080.
[15]白云凤,宫凯敏,王银洁,等.不同促渗剂对白芥子散贴剂体外透皮吸收效果的影响[J].中国实验方剂学杂志,2015,21(2):30-32.
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[17]银杉杉,汪艳秋,周国良,等.不同促渗剂对三威跌打风湿贴中柚皮苷体外透皮吸收的影响[J].中国实验方剂学杂志,2016,22(7):15-18.
[18]江敏瑜,闫丹,陈娇,等.三七跌打软膏的制备及体外透皮特性研究[J].中草药,2017,48(22):4639-4647.
[19] Riviere J E,Brooks J D. Predicting skin permeability from complex chemical mixtures:dependency of quantitative structure permeation relationships on biology of skin model used[J]. Toxicol Sci,2011,119(1):224-232.
[20]张倩,尹忠鹏,赵海南,等.微渗析技术用于金黄膏在大鼠体内经皮渗透性的初步研究[J].天津中医药大学学报,2012,31(3):151-153.
[21]冯乾坤,商学君,侯爽,等.中药凝胶贴膏与软膏剂的体外透皮特性比较研究[J].中国卫生工程学,2017,16(6):732-733.
[22]汪洁,魏颖,吕志阳,等.抗炎镇痛自发热凝胶膏剂的制备工艺研究[J].科技视界,2017(28):5-6.
[23]尹华,周爱珍,王知青.散瘀软膏成型工艺优选[J].中国实验方剂学杂志,2012,18(7):17-19.
[24]张博华,张义生,李杰,等.小儿咳喘贴黑膏药的制备工艺研究[J].中国药师,2015,18(2):332-334.
[25]何海珍,唐建飞,刘秋敏,等.黑膏药过敏性试验及去火毒工艺研究[J].浙江中医药大学学报,2009,33(1):124-125.
[26]储益平,居玲玲,高志芬,等.不同的成型工艺对关节止痛膏中挥发性成分的影响[J].世界中医药,2011,6(2):165-168.
[27]张康.复方祖师麻镇痛贴制备工艺和质量标准研究[D].成都:西华大学,2012.
[28]林媛媛,刘静,王冬梅,等. Box-Behnken试验设计法优化宝泻灵凝胶膏剂处方及其体外透皮特性研究[J].中草药,2014,45(9):1238-1244.
[29]吴东盼,田雪峰,蔡学军,等. D-最优混料设计优化寒痹舒凝胶膏剂的基质组成及其体外评价[J].中草药,2015,46(10):14. 4. 5-1453.
[30]严国鸿,林雄,李煌,等.双藤痹痛凝胶膏成型工艺研究[J].中国药房,2015,26(10):1383-1385.
[31]严国鸿,张玉琴,林雄,等.双藤痹痛凝胶膏剂对胶原诱导性关节炎模型大鼠血浆炎性因子和滑膜组织相关因子的影响[J].中国中医药信息杂志,2018,25(1):43-47.
[32]李慧敏.青鹏软膏干预佐剂性关节炎大鼠作用研究[D].天津:天津医科大学,2011.
[33]蔡辉,陆乐,赵智明.“以毒攻毒”在类风湿关节炎治疗中的运用[J].中医学报,2015,30(11):1664-1666.
[34]马振勇,李玉奎,赫金凤,等.复方乌头微乳大鼠皮肤长期毒性实验研究[J].中医学报,2017,32(12):2423-2425.
[35]袁伟彬,吴涵,黄晓冰,等.新工艺温通膏安全性评价研究[J].中药材,2017,40(8):1956-195.
[36]宋倩,刘健.成人Still病风湿热痹型30例临床治疗观察[J].中医药临床杂志,2015,27(11):1586-1589.
[37]张莉莉,曹玉举,郭家巧,等.黑膏药骨病活血膏中血竭的薄层色谱鉴别[J].中医外治杂志,2015,24(4):61-62.
[38]袁杰,刘道芳.接骨灵贴膏质量标准的研究[J].中成药,2016,38(3):575-578.
[39]段冀江,李沙沙,翁立冬,等. HPLC测定田七跌打风湿软膏中盐酸小檗碱的含量[J].中国实验方剂学杂志,2013,19(13):85-87.
[40]康阿龙,王卫峰,汤迎爽.椎间盘热融压敏胶贴膏质量标准的研究[J].药学服务与研究,2016,16(1):44-47.
[41]杜伟锋,姜东京,蔡宝昌.基于近红外光谱和多维谱效研究中药产地加工“发汗”[J].中成药,2014,36(11):2377-2380.
[42]王绚,陈军,蔡宝昌,等.优化马钱子总生物碱贴膏剂对大鼠佐剂性关节炎的治疗作用及其机制[J].中国实验方剂学杂志,2014,20(21):144-148.
[43]宋立华,刘淑芝.中药凝胶膏剂的研究进展分析[J].中国实验方剂学杂志,2015,21(22):133-136.
[44]曾照亿,刘佳,肖芳,等.挥发油3种加入方式对止痛凝胶贴膏剂基质及体外释放度的影响[J].中国实验方剂学杂志,2017,23(15):20-25.
[2] Taylor W J,Korendowych E,Nash P,et al. Drug use and toxicity in psoriatic disease:focus on methotrexate[J]. J Rheumatol,2008,35(7):1454-1457.
[3] Karaman A,Iraz M,Kirimlioglu H,et al. Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment[J]. Pediatr Surg Int,2006,22(9):701-708.
[4]国家药典委员会.中华人民共和国药典.一部[M].北京:中国医药科技出版社,2015:589-1591.
[5]徐敏敏,刘绍凡,王定菊.肿意膏穴位贴敷治疗急性痛风性关节炎(湿热痹阻证)的临床观察[J].中国中医急症,2018,27(1):112-114.
[6]周杨,朱红梅.辛味药研究现状与思考[J].中华中医药杂志,2013,28(6):1647-1650.
[7]王传邦,刘亭亭,牟丽秋,等.新型微乳载药系统的研究进展和应用前景[J].中国药业,2016,25(1):5-10.
[8]李学敏,王琼,兰颐,等.微乳技术对止痛凝胶膏剂中成分释放和含量变化的影响[J].中国中药杂志,2013,38(16):2614-2617.
[9]徐波,张来根,张农山,等.“MEMS微针促透‘易层’贴敷技术”治疗膝骨关节炎372例临床研究[J].时珍国医国药,2016,27(8):1912-1914.
[10]王琼.水包油型止痛微乳凝胶膏剂的优化与评价[D].北京:北京中医药大学,2014.
[11]赵立建,刘善新,苏酩,等.星点设计-效应面法优选活血巴布膏成型工艺[J].中国实验方剂学杂志,2016,22(13):19-22.
[12]黎丽.热熔压敏胶伤湿止痛膏的实验研究[D].北京:北京中医药大学,2012.
[13]朱静.橡胶膏剂低敏基质配方预混剂及应用研究[D].南京:南京中医药大学,2012.
[14]黄晓晨,宿树兰,钱大玮,等.不同促渗剂对少腹逐瘀方外用贴剂中效应成分群体外透皮吸收的影响[J].中草药,2014,45(21):3074-3080.
[15]白云凤,宫凯敏,王银洁,等.不同促渗剂对白芥子散贴剂体外透皮吸收效果的影响[J].中国实验方剂学杂志,2015,21(2):30-32.
[16]黄雨威,王利胜,兰小群,等.促渗剂对消喘巴布剂中白芥子体外透皮吸收特性的影响[J].中国医院药学杂志,2013,33(21):1754-1757.
[17]银杉杉,汪艳秋,周国良,等.不同促渗剂对三威跌打风湿贴中柚皮苷体外透皮吸收的影响[J].中国实验方剂学杂志,2016,22(7):15-18.
[18]江敏瑜,闫丹,陈娇,等.三七跌打软膏的制备及体外透皮特性研究[J].中草药,2017,48(22):4639-4647.
[19] Riviere J E,Brooks J D. Predicting skin permeability from complex chemical mixtures:dependency of quantitative structure permeation relationships on biology of skin model used[J]. Toxicol Sci,2011,119(1):224-232.
[20]张倩,尹忠鹏,赵海南,等.微渗析技术用于金黄膏在大鼠体内经皮渗透性的初步研究[J].天津中医药大学学报,2012,31(3):151-153.
[21]冯乾坤,商学君,侯爽,等.中药凝胶贴膏与软膏剂的体外透皮特性比较研究[J].中国卫生工程学,2017,16(6):732-733.
[22]汪洁,魏颖,吕志阳,等.抗炎镇痛自发热凝胶膏剂的制备工艺研究[J].科技视界,2017(28):5-6.
[23]尹华,周爱珍,王知青.散瘀软膏成型工艺优选[J].中国实验方剂学杂志,2012,18(7):17-19.
[24]张博华,张义生,李杰,等.小儿咳喘贴黑膏药的制备工艺研究[J].中国药师,2015,18(2):332-334.
[25]何海珍,唐建飞,刘秋敏,等.黑膏药过敏性试验及去火毒工艺研究[J].浙江中医药大学学报,2009,33(1):124-125.
[26]储益平,居玲玲,高志芬,等.不同的成型工艺对关节止痛膏中挥发性成分的影响[J].世界中医药,2011,6(2):165-168.
[27]张康.复方祖师麻镇痛贴制备工艺和质量标准研究[D].成都:西华大学,2012.
[28]林媛媛,刘静,王冬梅,等. Box-Behnken试验设计法优化宝泻灵凝胶膏剂处方及其体外透皮特性研究[J].中草药,2014,45(9):1238-1244.
[29]吴东盼,田雪峰,蔡学军,等. D-最优混料设计优化寒痹舒凝胶膏剂的基质组成及其体外评价[J].中草药,2015,46(10):14. 4. 5-1453.
[30]严国鸿,林雄,李煌,等.双藤痹痛凝胶膏成型工艺研究[J].中国药房,2015,26(10):1383-1385.
[31]严国鸿,张玉琴,林雄,等.双藤痹痛凝胶膏剂对胶原诱导性关节炎模型大鼠血浆炎性因子和滑膜组织相关因子的影响[J].中国中医药信息杂志,2018,25(1):43-47.
[32]李慧敏.青鹏软膏干预佐剂性关节炎大鼠作用研究[D].天津:天津医科大学,2011.
[33]蔡辉,陆乐,赵智明.“以毒攻毒”在类风湿关节炎治疗中的运用[J].中医学报,2015,30(11):1664-1666.
[34]马振勇,李玉奎,赫金凤,等.复方乌头微乳大鼠皮肤长期毒性实验研究[J].中医学报,2017,32(12):2423-2425.
[35]袁伟彬,吴涵,黄晓冰,等.新工艺温通膏安全性评价研究[J].中药材,2017,40(8):1956-195.
[36]宋倩,刘健.成人Still病风湿热痹型30例临床治疗观察[J].中医药临床杂志,2015,27(11):1586-1589.
[37]张莉莉,曹玉举,郭家巧,等.黑膏药骨病活血膏中血竭的薄层色谱鉴别[J].中医外治杂志,2015,24(4):61-62.
[38]袁杰,刘道芳.接骨灵贴膏质量标准的研究[J].中成药,2016,38(3):575-578.
[39]段冀江,李沙沙,翁立冬,等. HPLC测定田七跌打风湿软膏中盐酸小檗碱的含量[J].中国实验方剂学杂志,2013,19(13):85-87.
[40]康阿龙,王卫峰,汤迎爽.椎间盘热融压敏胶贴膏质量标准的研究[J].药学服务与研究,2016,16(1):44-47.
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