雷公藤外用制剂现代研究进展
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摘要
雷公藤具有抗炎、镇痛、抗肿瘤、免疫调节等多种药理活性,但其活性物质往往又是其毒性成分,因此如何实现减毒增效就成为雷公藤类制剂重要的研究方向。与传统口服给药相比,经皮给药制剂具有降低肝脏毒性、避免"峰谷现象"等优点,目前已成为雷公藤类制剂给药方式的研究热点。本文从雷公藤外用制剂的促透技术、不同促透技术的作用机制等方面进行综述,并提出雷公藤外用制剂面临的挑战和未来的研究方向。
Tripterygium wil fordii possesses various activities,including anti-inflammation,analgesia,antitumor and immunoregulation.However,the active substances are often toxic ingredients.For this reason,the research as how to decrease its toxicity and at the same time increase its efficacy has been an important research direction.As compared with the traditional route of oral medication,transdermal drug delivery has the advantages of less hepatotoxicity and absence of peak-valley drug concentration.Therefore,new route of Tripterygium wil fordii delivery has become an important hot spot in research.This paper made a comprehensive review from the perspectives of drug permeation-enhancing methods and related mechanisms involved in different drug permeation-enhancing techniques.At the same time,the paper also brought forth challenges and future direction in the research for Tripterygium wil fordii preparations for external use.
Tripterygium wil fordii possesses various activities,including anti-inflammation,analgesia,antitumor and immunoregulation.However,the active substances are often toxic ingredients.For this reason,the research as how to decrease its toxicity and at the same time increase its efficacy has been an important research direction.As compared with the traditional route of oral medication,transdermal drug delivery has the advantages of less hepatotoxicity and absence of peak-valley drug concentration.Therefore,new route of Tripterygium wil fordii delivery has become an important hot spot in research.This paper made a comprehensive review from the perspectives of drug permeation-enhancing methods and related mechanisms involved in different drug permeation-enhancing techniques.At the same time,the paper also brought forth challenges and future direction in the research for Tripterygium wil fordii preparations for external use.
引文
[1]沈子龙,李爽,谢启昆.雷公藤巴布剂透皮吸收研究[J].中国药科大学学报,1994,25(3):141-144.SHEN ZiLong,LI Shuang,XIE QiKun.Study on percutaneous absorption of Tripterygium wilfordii PAP patcher(TWPP)with radioisotope tracing technique[J].J China Pharm Univ,1994,25(3):141-144.In Chinese with English abstract.
[2]陈凌云,张卫兵,张丽萍.类风关巴布剂体外透皮吸收研究[J].医药导报,2004,23(7):444-445.CHEN LingYun,ZHANG WeiBing,ZHANG LiPing.Experimental study on transdermal delivery of rhemeutoid-arthrosis Babugao[J].Herald Med,2004,23(7):444-445.In Chinese with English abstract.
[3]万军梅,郭群.雷公藤巴布剂的抗炎免疫药理作用研究[J].武汉职业技术学院学报,2008,7(5):77-79.WAN JunMei,GUO Qun.Study on anti-inflammatory and immune effects of Tripterygium wilfordi PAP patcher(TWPP)[J].J Wuhan Inst Technol,2008,7(5):77-79.In Chinese with English abstract.
[4]张宁,徐艳明,祁永华,等.外用凝胶剂研究进展[J].黑龙江医药,2010,23(1):92-93.ZHANG Ning,XU YanMing,QI YongHua,et al.Research advances in external use gels[J].Heilongjiang Med J,2010,23(1):92-93.In Chinese.
[5]熊欣,刘淑芝,顼佳音,等.新型载体经皮凝胶剂的研究进展[J].中国实验方剂学杂志,2011,17(22):244-249.XIONG Xin,LIU ShuZhi,XU JiaYin,et al.Development of transdermal gels with novel drug carriers[J].Chin J Exp Tradit Med Formul,2011,17(22):244-249.In Chinese with English abstract.
[6]管咏梅,丁莹,张霄潇,等.雷公藤凝胶与软膏中雷公藤内酯的经皮渗透性比较研究[J].中国药师,2008,11(4):373-375.GUAN YongMei,DING Ying,ZHANG XiaoXiao,et al.Study on percutaneous permeation of triptolide in gel and ointment[J].China Pharmacist,2008,11(4):373-375.In Chinese with English abstract.
[7]余雅婷,朱卫丰,陈丽华,等.雷公藤甲素微乳凝胶的制备及体外透皮性能考察[J].中国医院药学杂志,2016,36(13):1087-1091.YU YaTing,ZHU WeiFeng,CHEN LiHua,et al.Preparation of triptolide microemulsion-based gel and investigation of its in vitro percutanous permeability[J].Chin Hosp Pharm J,2016,36(13):1087-1091.In Chinese with English abstract.
[8]龙正海,韦登明,杜纪斌.雷公藤内酯醇复方乳膏剂皮肤毒理及其透皮吸收性能研究[J].中成药,2010,32(2):213-218.LONG ZhengHai,WEI DengMing,DU JiBin.Dermal toxicology and absorption of triptolide compound cream[J].Chin Tradit Patent Med,2010,32(2):213-218.In Chinese with English abstract.
[9]杜丽娜,金义光.经皮给药系统研究进展[J].国际药学研究杂志,2013,40(4):379-385.DU LiNa,JIN YiGuang.Progress of transdermal drug delivery systems[J].J Int Pharm Res,2013,40(4):379-385.In Chinese with English abstract.
[10]陈贵,徐坤,豆婧婧,等.微针条件下雷公藤甲素不同剂型对类风湿性关节炎大鼠皮肤损伤的研究[J].中国药学杂志,2012,47(6):435-438.CHEN Gui,XU Kun,DOU Jingjing,et al.Effects of different triptolide formulations given by MEMS micro-needles on skin injury of rheumatoid arthritis rats[J].Chin Pharm J,2012,47(6):435-438.In Chinese with English abstract.
[11]ZUO Jing,DU LiNa,LI Miao,et al.Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs[J].Int J Pharm,2014,466(1-2):76-82.
[12]Crevenna R,Burian A,Oesterreicher Z.Iontophoresis driven concentrations of topically administered diclofenac in skeletal muscle and blood of healthy subjects[J].Eur J Clin Pharmacol,2015,71(11):1359-1364.
[13]周伟,闫娟.雷公藤离子导入治疗膝骨关节炎疗效观察[J].中国煤炭工业医学杂志,2006,9(10):1065-1066.ZHOU Wei,YAN Juan.Effect of Tripterygium wilfordii with iontophoresis in the treatment of knee osteoarthritis[J].Chin J Coal Ind Med,2006,9(10):1065-1066.In Chinese.
[14]El-Nabarawi M A,Bendas E R,El Rehem R T,et al.Transdermal drug delivery of paroxetine through lipid-vesicular formulation to augment its bioavailability[J].Int J Pharm,2013,443(1-2):307-317.
[15]Carbone C,Leonardi A,Cupri S,et al.Pharmaceutical and biomedical applications of lipid-based nanocarriers[J].Pharm Pat Anal,2014,3(2):199-215.
[16]ZHAI YingJie,ZHAI GuangXi.Advances in lipid-based colloid systems as drug carrier for topic delivery[J].J Control Release,2014,193:90-99.
[17]李瀚旻,兰少波,常明向.雷公藤甲素脂质体透皮制剂对Ⅱ型胶原诱发的关节炎的影响[J].中草药,2013,44(2):199-202.LI HanMin,LAN ShaoBo,CHANG MingXiang.Effects of transdermal liposome preparation of triptolide on arthritis induced by collagenⅡ[J].Chin Tradit Herb Drugs,2013,44(2):199-202.In Chinese with English abstract.
[18]李瀚旻,罗春华,晏雪生,等.雷公藤甲素对人肝癌Bel-7402细胞增殖及凋亡的影响[J].中华中医药学刊,2009,27(1):8-10.LI HanMin,LUO ChunHua,YAN XueSheng,et al.Effect of tripolide on human hepatic cancer Bel-7402cell proliferation and apoptosis[J].Chin Arch Tradit Chin Med,2009,27(1):8-10.In Chinese with English abstract.
[19]常明向,李瀚旻,兰少波.雷公藤甲素脂质体透皮制剂对H-22实体瘤的影响[J].时珍国医国药,2012,23(5):1157-1159.CHANG MingXiang,LI HanMin,LAN ShaoBo.Effects of transdermal preparation of tripolide liposomes on H-22solid tumor[J].Lishizhen Med Mat Medica Res,2012,23(5):1157-1159.In Chinese.
[20]Klang V,Matsko N,Zimmermann A M,et al.Enhancement of stability and skin permeation by sucrose stearate and cyclodextrins in progesterone nanoemulsions[J].Int J Pharm,2010,393(1-2):152-160.
[21]张少燕,石森林.雷公藤及其提取物的制剂新技术与新剂型研究进展[J].海峡药学,2012,24(10):9-12.ZHANG ShaoYan,SHI SenLin.Research progress on advanced pharmaceutical preparation and technology of Tripterygium and its extracts[J].Strait Pharm J,2012,24(10):9-12.In Chinese with English abstract.
[22]顾清,尤本明,杨帝顺,等.基于纳米乳-凝胶技术的雷公藤多苷纳米载体的制备及药效学研究[J].中国中药杂志,2015,40(1):73-78.GU Qing,YOU BenMing,YANG DiShun,et al.Development of Tripterygiumglycosides nano-carries based on“nanoemulsion-gels”and its pharmacodynamics[J].China J Chin Mat Med,2015,40(1):73-78.In Chinese with English abstract.
[23]ner M.Preparation,characterization and physic-chemical property of solid lipid nanoparticles(SLN)and nanostructured lipid carriers(NLC):their benefits as colloidal drug carrier systems[J].Pharmazie,2006,61(5):375-386.
[24]梅之南,杨祥良,杨亚江,等.雷公藤内酯醇固体脂质纳米粒经皮渗透及抗炎活性的研究[J].中国药学杂志,2003,38(11):854-857.MEI ZhiNan,YANG XiangLiang,YANG YaJiang,et al.Study on triptolide loaded solid lipid nanoparticle for transdermal delivery and its anti-inflammatory activity[J].Chin Pharm J,2003,38(11):854-857.In Chinese with English abstract.
[25]梅之南,杨亚江,徐辉碧,等.固体脂质纳米粒降低雷公藤内酯醇肝毒性的实验研究[J].中草药,2003,34(9):817-819.MEI ZhiNan,YANG YaJiang,XU HuiBi,et al.Experimental research on triptolide solid lipid nanoparticle for decreasing liver toxicity of triptolide[J].Chin Tradit Herb Drugs,2003,34(9):817-819.In Chinese with English abstract.
[26]Pardeike J,Hommoss A,Müller R H.Lipid nanoparticles(SLN,NLC)in cosmetic and pharmaceutical dermal products[J].Int J Pharm,2009,366(1-2):170-184.
[27]袁菱,周蕾,陈彦,等.雷公藤红素纳米结构脂质载体的制备及其理化性质考察[J].中成药,2013,35(9):2023-2027.YUAN Ling,ZHOU Lei,CHEN Yan,et al.Preparation of tripterine-loaded nanostructured lipid carrier and its physicochemical property evaluation[J].Chin Tradit Pat Med,2013,35(9):2023-2027.In Chinese.
[28]袁菱,周蕾,陈彦,等.雷公藤红素纳米结构脂质载体的制备及其体外透皮研究[J].中草药,2012,43(8):1514-1518.YUAN Ling,ZHOU Lei,CHEN Yan,et al.Preparation of tripterine-loaded nanostructured lipid carrier and its in vitro transdermal absorption[J].Chin Tradit Herb Drugs,2012,43(8):1514-1518.In Chinese with English abstract.
[29]Parhi R,Suresh P,Mondal S,et al.Novel penetration enhancers for skin applications:a review[J].Curr Drug Deliv,2012,9(2):219-230.
[30]Benson H A.Transdermal drug delivery:penetration enhancement techniques[J].Curr Drug Deliv,2005,2(1):23-33.
[31]Azagury A,Khoury L,Enden G,et al.Ultrasound mediated transdermal drug delivery[J].Adv Drug Deliv Rev,2014,72:127-143.
[32]Karande P,Jain A,Mitragotri S.Discovery of transdermal penetration enhancers by high-throughput screening[J].Nat Biotechnol,2004,22(2):192-197.
[33]Han T,Das D B.Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation:a review[J].Eur J Pharm Biopharm,2015,89:312-328.
[2]陈凌云,张卫兵,张丽萍.类风关巴布剂体外透皮吸收研究[J].医药导报,2004,23(7):444-445.CHEN LingYun,ZHANG WeiBing,ZHANG LiPing.Experimental study on transdermal delivery of rhemeutoid-arthrosis Babugao[J].Herald Med,2004,23(7):444-445.In Chinese with English abstract.
[3]万军梅,郭群.雷公藤巴布剂的抗炎免疫药理作用研究[J].武汉职业技术学院学报,2008,7(5):77-79.WAN JunMei,GUO Qun.Study on anti-inflammatory and immune effects of Tripterygium wilfordi PAP patcher(TWPP)[J].J Wuhan Inst Technol,2008,7(5):77-79.In Chinese with English abstract.
[4]张宁,徐艳明,祁永华,等.外用凝胶剂研究进展[J].黑龙江医药,2010,23(1):92-93.ZHANG Ning,XU YanMing,QI YongHua,et al.Research advances in external use gels[J].Heilongjiang Med J,2010,23(1):92-93.In Chinese.
[5]熊欣,刘淑芝,顼佳音,等.新型载体经皮凝胶剂的研究进展[J].中国实验方剂学杂志,2011,17(22):244-249.XIONG Xin,LIU ShuZhi,XU JiaYin,et al.Development of transdermal gels with novel drug carriers[J].Chin J Exp Tradit Med Formul,2011,17(22):244-249.In Chinese with English abstract.
[6]管咏梅,丁莹,张霄潇,等.雷公藤凝胶与软膏中雷公藤内酯的经皮渗透性比较研究[J].中国药师,2008,11(4):373-375.GUAN YongMei,DING Ying,ZHANG XiaoXiao,et al.Study on percutaneous permeation of triptolide in gel and ointment[J].China Pharmacist,2008,11(4):373-375.In Chinese with English abstract.
[7]余雅婷,朱卫丰,陈丽华,等.雷公藤甲素微乳凝胶的制备及体外透皮性能考察[J].中国医院药学杂志,2016,36(13):1087-1091.YU YaTing,ZHU WeiFeng,CHEN LiHua,et al.Preparation of triptolide microemulsion-based gel and investigation of its in vitro percutanous permeability[J].Chin Hosp Pharm J,2016,36(13):1087-1091.In Chinese with English abstract.
[8]龙正海,韦登明,杜纪斌.雷公藤内酯醇复方乳膏剂皮肤毒理及其透皮吸收性能研究[J].中成药,2010,32(2):213-218.LONG ZhengHai,WEI DengMing,DU JiBin.Dermal toxicology and absorption of triptolide compound cream[J].Chin Tradit Patent Med,2010,32(2):213-218.In Chinese with English abstract.
[9]杜丽娜,金义光.经皮给药系统研究进展[J].国际药学研究杂志,2013,40(4):379-385.DU LiNa,JIN YiGuang.Progress of transdermal drug delivery systems[J].J Int Pharm Res,2013,40(4):379-385.In Chinese with English abstract.
[10]陈贵,徐坤,豆婧婧,等.微针条件下雷公藤甲素不同剂型对类风湿性关节炎大鼠皮肤损伤的研究[J].中国药学杂志,2012,47(6):435-438.CHEN Gui,XU Kun,DOU Jingjing,et al.Effects of different triptolide formulations given by MEMS micro-needles on skin injury of rheumatoid arthritis rats[J].Chin Pharm J,2012,47(6):435-438.In Chinese with English abstract.
[11]ZUO Jing,DU LiNa,LI Miao,et al.Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs[J].Int J Pharm,2014,466(1-2):76-82.
[12]Crevenna R,Burian A,Oesterreicher Z.Iontophoresis driven concentrations of topically administered diclofenac in skeletal muscle and blood of healthy subjects[J].Eur J Clin Pharmacol,2015,71(11):1359-1364.
[13]周伟,闫娟.雷公藤离子导入治疗膝骨关节炎疗效观察[J].中国煤炭工业医学杂志,2006,9(10):1065-1066.ZHOU Wei,YAN Juan.Effect of Tripterygium wilfordii with iontophoresis in the treatment of knee osteoarthritis[J].Chin J Coal Ind Med,2006,9(10):1065-1066.In Chinese.
[14]El-Nabarawi M A,Bendas E R,El Rehem R T,et al.Transdermal drug delivery of paroxetine through lipid-vesicular formulation to augment its bioavailability[J].Int J Pharm,2013,443(1-2):307-317.
[15]Carbone C,Leonardi A,Cupri S,et al.Pharmaceutical and biomedical applications of lipid-based nanocarriers[J].Pharm Pat Anal,2014,3(2):199-215.
[16]ZHAI YingJie,ZHAI GuangXi.Advances in lipid-based colloid systems as drug carrier for topic delivery[J].J Control Release,2014,193:90-99.
[17]李瀚旻,兰少波,常明向.雷公藤甲素脂质体透皮制剂对Ⅱ型胶原诱发的关节炎的影响[J].中草药,2013,44(2):199-202.LI HanMin,LAN ShaoBo,CHANG MingXiang.Effects of transdermal liposome preparation of triptolide on arthritis induced by collagenⅡ[J].Chin Tradit Herb Drugs,2013,44(2):199-202.In Chinese with English abstract.
[18]李瀚旻,罗春华,晏雪生,等.雷公藤甲素对人肝癌Bel-7402细胞增殖及凋亡的影响[J].中华中医药学刊,2009,27(1):8-10.LI HanMin,LUO ChunHua,YAN XueSheng,et al.Effect of tripolide on human hepatic cancer Bel-7402cell proliferation and apoptosis[J].Chin Arch Tradit Chin Med,2009,27(1):8-10.In Chinese with English abstract.
[19]常明向,李瀚旻,兰少波.雷公藤甲素脂质体透皮制剂对H-22实体瘤的影响[J].时珍国医国药,2012,23(5):1157-1159.CHANG MingXiang,LI HanMin,LAN ShaoBo.Effects of transdermal preparation of tripolide liposomes on H-22solid tumor[J].Lishizhen Med Mat Medica Res,2012,23(5):1157-1159.In Chinese.
[20]Klang V,Matsko N,Zimmermann A M,et al.Enhancement of stability and skin permeation by sucrose stearate and cyclodextrins in progesterone nanoemulsions[J].Int J Pharm,2010,393(1-2):152-160.
[21]张少燕,石森林.雷公藤及其提取物的制剂新技术与新剂型研究进展[J].海峡药学,2012,24(10):9-12.ZHANG ShaoYan,SHI SenLin.Research progress on advanced pharmaceutical preparation and technology of Tripterygium and its extracts[J].Strait Pharm J,2012,24(10):9-12.In Chinese with English abstract.
[22]顾清,尤本明,杨帝顺,等.基于纳米乳-凝胶技术的雷公藤多苷纳米载体的制备及药效学研究[J].中国中药杂志,2015,40(1):73-78.GU Qing,YOU BenMing,YANG DiShun,et al.Development of Tripterygiumglycosides nano-carries based on“nanoemulsion-gels”and its pharmacodynamics[J].China J Chin Mat Med,2015,40(1):73-78.In Chinese with English abstract.
[23]ner M.Preparation,characterization and physic-chemical property of solid lipid nanoparticles(SLN)and nanostructured lipid carriers(NLC):their benefits as colloidal drug carrier systems[J].Pharmazie,2006,61(5):375-386.
[24]梅之南,杨祥良,杨亚江,等.雷公藤内酯醇固体脂质纳米粒经皮渗透及抗炎活性的研究[J].中国药学杂志,2003,38(11):854-857.MEI ZhiNan,YANG XiangLiang,YANG YaJiang,et al.Study on triptolide loaded solid lipid nanoparticle for transdermal delivery and its anti-inflammatory activity[J].Chin Pharm J,2003,38(11):854-857.In Chinese with English abstract.
[25]梅之南,杨亚江,徐辉碧,等.固体脂质纳米粒降低雷公藤内酯醇肝毒性的实验研究[J].中草药,2003,34(9):817-819.MEI ZhiNan,YANG YaJiang,XU HuiBi,et al.Experimental research on triptolide solid lipid nanoparticle for decreasing liver toxicity of triptolide[J].Chin Tradit Herb Drugs,2003,34(9):817-819.In Chinese with English abstract.
[26]Pardeike J,Hommoss A,Müller R H.Lipid nanoparticles(SLN,NLC)in cosmetic and pharmaceutical dermal products[J].Int J Pharm,2009,366(1-2):170-184.
[27]袁菱,周蕾,陈彦,等.雷公藤红素纳米结构脂质载体的制备及其理化性质考察[J].中成药,2013,35(9):2023-2027.YUAN Ling,ZHOU Lei,CHEN Yan,et al.Preparation of tripterine-loaded nanostructured lipid carrier and its physicochemical property evaluation[J].Chin Tradit Pat Med,2013,35(9):2023-2027.In Chinese.
[28]袁菱,周蕾,陈彦,等.雷公藤红素纳米结构脂质载体的制备及其体外透皮研究[J].中草药,2012,43(8):1514-1518.YUAN Ling,ZHOU Lei,CHEN Yan,et al.Preparation of tripterine-loaded nanostructured lipid carrier and its in vitro transdermal absorption[J].Chin Tradit Herb Drugs,2012,43(8):1514-1518.In Chinese with English abstract.
[29]Parhi R,Suresh P,Mondal S,et al.Novel penetration enhancers for skin applications:a review[J].Curr Drug Deliv,2012,9(2):219-230.
[30]Benson H A.Transdermal drug delivery:penetration enhancement techniques[J].Curr Drug Deliv,2005,2(1):23-33.
[31]Azagury A,Khoury L,Enden G,et al.Ultrasound mediated transdermal drug delivery[J].Adv Drug Deliv Rev,2014,72:127-143.
[32]Karande P,Jain A,Mitragotri S.Discovery of transdermal penetration enhancers by high-throughput screening[J].Nat Biotechnol,2004,22(2):192-197.
[33]Han T,Das D B.Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation:a review[J].Eur J Pharm Biopharm,2015,89:312-328.