中药透皮给药系统研究进展及其新剂型的应用
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摘要
作为当今药物传输系统研究的热点,中药透皮给药系统避免了口服给药产生的肝脏首过效应,提高药物的生物利用度、减少药物对胃肠道的刺激同时提高患者的顺应性,以其显著的疗效和用药安全、方便等独特的优势日益受到患者的青睐及研发人员的重视。通过查阅近年来中英文相关文献,作者总结出目前常用的中药透皮给药促渗透技术的物理方法和化学方法以及体内外评价方法,并对其新剂型的应用进行综述。文章对近年来中药透皮给药系统的研究与应用情况进行归纳和总结,同时展望了中药透皮给药系统的发展前景,以期为后续中药透皮吸收的研究和中药透皮给药系统新剂型的开发提供参考,为我国的中药现代化发展提供新思路和新方法。
As a hotspot in the research of drug delivery systems,transdermal delivery system of traditional Chinese medicine avoids the first-pass effect of liver after oral administration,improves drug bioavailability,reduces the stimulation to gastrointestinal tract and improves the compliance of patients. Traditional Chinese medicine transdermal drug delivery system has drawn more and more attention of patients and researchers due to its significant effect and medication safety,convenience and other unique advantages. Through reviewing relevant Chinese and English literatures in recent years,the authors summed up the physical and chemical methods of promoting the transdermal penetration of traditional Chinese medicine and in vitro and in vivo evaluation methods,and reviewed the application of new formulations. The article also looked forward to the development prospects of transdermal drug delivery system of traditional Chinese medicine. It is expected to provide reference for the research of transdermal absorption of traditional Chinese medicine and the development of dosage forms and provide new ideas and new methods for the modernization of traditional Chinese medicine in our country.
As a hotspot in the research of drug delivery systems,transdermal delivery system of traditional Chinese medicine avoids the first-pass effect of liver after oral administration,improves drug bioavailability,reduces the stimulation to gastrointestinal tract and improves the compliance of patients. Traditional Chinese medicine transdermal drug delivery system has drawn more and more attention of patients and researchers due to its significant effect and medication safety,convenience and other unique advantages. Through reviewing relevant Chinese and English literatures in recent years,the authors summed up the physical and chemical methods of promoting the transdermal penetration of traditional Chinese medicine and in vitro and in vivo evaluation methods,and reviewed the application of new formulations. The article also looked forward to the development prospects of transdermal drug delivery system of traditional Chinese medicine. It is expected to provide reference for the research of transdermal absorption of traditional Chinese medicine and the development of dosage forms and provide new ideas and new methods for the modernization of traditional Chinese medicine in our country.
引文
[1]梁佳敏,李楠,徐海蓉,等.经皮给药系统的体外释放、透皮特性及体内药动学研究进展[J].武警后勤学院学报,2013,22(12):1137-1140.
[2]庞晓晨,成睿珍,赵静.肛肠科外用凝胶剂的制备及其体外透皮性能考察[J].中国全科医学,2018,21(6):737-740.
[3]庞晓晨,成睿珍,李玥,等.赵静肛洗二号中药软膏剂皮肤刺激性考察及质量控制研究[J].中国中医基础医学杂志,2018,24(1):118-121.
[4] ZHANG N,WU Y,XING R,et al. Effect of ultrasound-enhanced transdermal drug delivery efficiency of nanoparticles and brucine[J]. Biomed Res Int,2017:1-8.
[5] VITORINO C,SOUSA J,PAIS A. Overcoming the skin permeation barrier:challenges and opportunities[J]. Curr Pharm Des,2015,21(20):2698-2712.
[6] ALKILANI AZ,MCCRUDDEN MT,DONNELLY RF. Transdermal drug delivery:innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum[J].Pharmaceutics,2015,7(4):438-470.
[7]姚俊宏,蒋秋冬,陈军,等. 21种辛味中药挥发油透皮促渗效果的药性规律分析[J].中国实验方剂学杂志,2018,24(1):1-7.
[8] AMJADI M,MOSTAGHACI B,SITTIM. Recent advances in skin penetration enhancers for transdermal gene and drug delivery[J]. Curr Gene Ther,2017,17(2):139-146.
[9] SUBBIAH N,CAMPAGNA J,SPILMAN P,et al. Deformable nanovesicles synthesized through an adaptable microfluidic platform for enhanced localized transdermal drug delivery[J]. J Drug Deliv,2017:4759839.
[10]张志勇,孙延斌,杨金永.经皮离子导入技术给药的研究进展[J].牡丹江医学院学报,2016,37(4):119-122.
[11] BOGNER RH,BANAGA AK. Iontophoresis and phonophoresis[J]. US Pharm,1994,19(8):10-26.
[12]杜丽娜,刘笑,贾俊伟,等.离子导入对阿魏酸透皮吸收的促进作用[J].国际药学研究杂志,2014,41(5):595-598.
[13] ZOREC B,JELENC J,MIKLAVCIA D,et al. Ultrasound and electric pulses for transdermal drug delivery enhancement:ex vivo assessment of methods with in vivo oriented experimental protocols[J]. Int J Pharm,2015,490(1-2):65-73.
[14]郝静,崔广伟.丹参注射液电离子导入治疗玻璃体积血的疗效观察[J].国际眼科杂志,2013,13(11):2281-2283.
[15] ITA K. Recent progress in transdermal sonophoresis[J]. Pharm Dev Technol,2017,22(4):458-466.
[16]梁哲浩,梁文权,孙华琴.超声波促进盐酸利多卡因经皮渗透的研究[J].中国现代应用药学,2014,31(4):437-441.
[17]孙芳,郑秋惠,王淑萍,等.扶正抑瘤方超声导入辅助治疗原发性肝癌的临床分析[J].中国实验方剂学杂志,2016,22(1):181-185.
[18]陈慧芳,吴其国,胡叶青.中药经皮给药制剂中促透剂的研究进展[J].广西中医药大学学报,2017,20(1):69-72.
[19] ITA KB. Chemical penetration enhancers for transdermal drug delivery-success and challenges[J]. Curr Drug Deliv,2015,12(6):645-651.
[20] MAJELLA EL. Skin penetration enhancers[J]. Int J Pharm,2013,447(2):12-21.
[21] KUMAR S,ZAKREWSKY M,CHEN M,et al. Peptides as skin penetration enhancers:mechanisms of action[J]. J Control Release,2015,199:168-178.
[22]刘亭亭,王传邦,牟丽秋,等.壳聚糖及其衍生物作为促渗剂在经皮给药系统中的研究进展[J].中南药学,2015,13(6):624-627.
[23] JANA S,MANNA S,NAYAK AK,et al. Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery[J]. Colloids Surf B Biointerfaces,2014,114(8):36-44.
[24]徐俊鸿,陈地灵,李正平,等.氮酮对消炎止痒搽剂中黄芩苷透皮吸收的影响研究[J].今日药学,2014,24(2):87-92.
[25]陈军,刘培,蒋秋冬,等.中药挥发油作为透皮吸收促进剂的现状与展望[J].中草药,2014,45(24):3651-3655.
[26] LAN Y,WU Q,MAO YQ,et al. Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum maxim. As a natural transdermal penetration enhancer[J]. J Zhejiang Univ Sci B,2014,15(2):153-164.
[27]单玲玲,靳光乾,王平,等.中药透皮吸收促进剂研究[J].辽宁中医药大学学报,2013,15(5):112-114.
[28]温亚,韩彬,戴王强,等.薄荷醇对芍药普透皮吸收作用的影响[J].湖南中医杂志,2014,30(5):128-130.
[29] DE SPIEQELEER B,BOONEN J,MALYSHEVA SV,et al.Skin penetration enhancing properties of the plant N-alkylamide spilanthol[J]. J Ethnopharm,2013,148(1):117-125.
[30]耿志霞,蒋春茂,刘腾飞,等.伊维菌素体外透皮吸收影响因素的研究[J].扬州大学学报,2013,34(2):20-24.
[31]李琳,杨晓艳,杨野,等.三七素体外经皮渗透特性研究[J].中草药,2015,46(17):2563-2567.
[32] BALAZS B,VIZSERALEK G,BERKO S,et al. Investigation of the efficacy of transdermal penetration enhancers through the use of human skin and a skin mimic artificial membrane[J]. J Pharm Sci,2016,105(3):1134-1140.
[33] CLARKE LL. A guide to ussing chamber studies of mouse intestine[J]. Am J Physiol Gastrointest Liver Physiol,2009,296(6):1151-1166.
[34]顾星,姚少姿,皮佳鑫,等.基于Ussing Chamber技术的红景天苷大鼠肠黏膜透过性研究[J].天津中医药,2016,33(11):689-693.
[35] ERDO F,HASHIMOTO N,KARVALY G,et al. Critical evaluation and methodological positioning of the transdermal microdialysis technique:a review[J]. J Control Release,2016,233:147-161.
[36]李得堂,吴晓贞,何嘉仑,等.在体皮肤微透析技术和HPLC测定吴茱萸碱和吴茱萸次碱的透皮释药特性[J].中国药学杂志,2015,50(3):239-243.
[37] XIE F,CHAI JK,HU Q,et al. Transdermal permeation of drugs with differing lipophilicity:effect of penetration enhancer camphor[J]. Int J Pharm,2016,507(1-2):90-101.
[38]戴居云,赵玲,王颖华,等.穴位透皮贴剂中丹参酮ⅡA的经皮吸收速率研究[J].现代中西医结合杂志,2004,13(24):3245-3248.
[39]李文华,王英姿,骆声秀,等.苦参总碱纳米乳和苦参总碱纳米乳凝胶的透皮机制研究[J].中草药,2017,48(3):484-489.
[40] VITORINO C,ALMEIDA A,SOUSA J,et al. Passive and active strategies for transdermal delivery using co-encapsulating nanostructured lipid carriers:in vitro vs in vivo studies[J]. Eur J Pharm Biopharm,2014,86(2):133-144.
[41] GOMAA YA,GARLAND MJ,MCINNES FJ,et al. Microneedle/nanoencapsulation-mediated transdermal delivery:mechanistic insights[J]. Eur J Pharm Biopharm,2014,86(2):145-155.
[42]梁震野,杨建苗,杜立峰,等.肉桂提取物醇质体凝胶经皮给药研究[J].中国现代应用药学,2013,30(11):1202-1206.
[43]王慧,张晓红,张燕,等.尼古丁乙醇脂质体的制备与体外透皮特性研究[J].中国药房,2015,26(19):2717-2720.
[44] THAKKAR PJ,MADAN P,LIN S. Transdermal delivery of diclofenac using water-in-oil microemulsion:formulation andmechanistic approach of drug skin permeation[J]. Pharm Dev Technol,2014,19(3):373-384.
[45]高玉红,庞淑华.微乳透皮给药机制及影响吸收的因素[J].饲料博览,2014,26(6):37-40.
[46]赵晶,金凯,宋光杰,等.水杨酸微乳的制备及其体外透皮吸收研究[J].中国药房,2015,26(1):112-114.
[47]章烨雯,王琼,于竞新,等.止痛微乳凝胶膏的制备及体外评价[J].北京中医药大学学报,2015,38(4):253-259.
[48] LADEMANN J,RICHTER H,MEINKE MC,et al. Drug delivery with topically applied nanoparticles:science fiction or reality[J]. Skin Pharmacol Physiol,2013,26(4-6):227-233.
[49] TACHAPRUTINUM A,MEINKE MC,RICHTER H,et al.Comparison of the skin penetration of Garcinia mangostana extract in particulate and non-particulate form[J]. Eur J Pharm Biop Harm,2014,88(2):307-313.
[50]肖志方.美洛昔康固体脂质纳米粒的制备及体外透皮研究[J].中国药师,2015,18(9):1512-1515.
[51]郭涤亮,徐萍蔚,王亚敏.皮肤局部外用仿制药质量等同性评价的一般考虑[J].中国新药杂志,2018,27(18):2116-2120.
[52]陈斌辉,杨赛琳,吴素香.皮肤科局部用药新载体的研究进展[J].中国现代应用药学,2018,35(4):615-621.
[2]庞晓晨,成睿珍,赵静.肛肠科外用凝胶剂的制备及其体外透皮性能考察[J].中国全科医学,2018,21(6):737-740.
[3]庞晓晨,成睿珍,李玥,等.赵静肛洗二号中药软膏剂皮肤刺激性考察及质量控制研究[J].中国中医基础医学杂志,2018,24(1):118-121.
[4] ZHANG N,WU Y,XING R,et al. Effect of ultrasound-enhanced transdermal drug delivery efficiency of nanoparticles and brucine[J]. Biomed Res Int,2017:1-8.
[5] VITORINO C,SOUSA J,PAIS A. Overcoming the skin permeation barrier:challenges and opportunities[J]. Curr Pharm Des,2015,21(20):2698-2712.
[6] ALKILANI AZ,MCCRUDDEN MT,DONNELLY RF. Transdermal drug delivery:innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum[J].Pharmaceutics,2015,7(4):438-470.
[7]姚俊宏,蒋秋冬,陈军,等. 21种辛味中药挥发油透皮促渗效果的药性规律分析[J].中国实验方剂学杂志,2018,24(1):1-7.
[8] AMJADI M,MOSTAGHACI B,SITTIM. Recent advances in skin penetration enhancers for transdermal gene and drug delivery[J]. Curr Gene Ther,2017,17(2):139-146.
[9] SUBBIAH N,CAMPAGNA J,SPILMAN P,et al. Deformable nanovesicles synthesized through an adaptable microfluidic platform for enhanced localized transdermal drug delivery[J]. J Drug Deliv,2017:4759839.
[10]张志勇,孙延斌,杨金永.经皮离子导入技术给药的研究进展[J].牡丹江医学院学报,2016,37(4):119-122.
[11] BOGNER RH,BANAGA AK. Iontophoresis and phonophoresis[J]. US Pharm,1994,19(8):10-26.
[12]杜丽娜,刘笑,贾俊伟,等.离子导入对阿魏酸透皮吸收的促进作用[J].国际药学研究杂志,2014,41(5):595-598.
[13] ZOREC B,JELENC J,MIKLAVCIA D,et al. Ultrasound and electric pulses for transdermal drug delivery enhancement:ex vivo assessment of methods with in vivo oriented experimental protocols[J]. Int J Pharm,2015,490(1-2):65-73.
[14]郝静,崔广伟.丹参注射液电离子导入治疗玻璃体积血的疗效观察[J].国际眼科杂志,2013,13(11):2281-2283.
[15] ITA K. Recent progress in transdermal sonophoresis[J]. Pharm Dev Technol,2017,22(4):458-466.
[16]梁哲浩,梁文权,孙华琴.超声波促进盐酸利多卡因经皮渗透的研究[J].中国现代应用药学,2014,31(4):437-441.
[17]孙芳,郑秋惠,王淑萍,等.扶正抑瘤方超声导入辅助治疗原发性肝癌的临床分析[J].中国实验方剂学杂志,2016,22(1):181-185.
[18]陈慧芳,吴其国,胡叶青.中药经皮给药制剂中促透剂的研究进展[J].广西中医药大学学报,2017,20(1):69-72.
[19] ITA KB. Chemical penetration enhancers for transdermal drug delivery-success and challenges[J]. Curr Drug Deliv,2015,12(6):645-651.
[20] MAJELLA EL. Skin penetration enhancers[J]. Int J Pharm,2013,447(2):12-21.
[21] KUMAR S,ZAKREWSKY M,CHEN M,et al. Peptides as skin penetration enhancers:mechanisms of action[J]. J Control Release,2015,199:168-178.
[22]刘亭亭,王传邦,牟丽秋,等.壳聚糖及其衍生物作为促渗剂在经皮给药系统中的研究进展[J].中南药学,2015,13(6):624-627.
[23] JANA S,MANNA S,NAYAK AK,et al. Carbopol gel containing chitosan-egg albumin nanoparticles for transdermal aceclofenac delivery[J]. Colloids Surf B Biointerfaces,2014,114(8):36-44.
[24]徐俊鸿,陈地灵,李正平,等.氮酮对消炎止痒搽剂中黄芩苷透皮吸收的影响研究[J].今日药学,2014,24(2):87-92.
[25]陈军,刘培,蒋秋冬,等.中药挥发油作为透皮吸收促进剂的现状与展望[J].中草药,2014,45(24):3651-3655.
[26] LAN Y,WU Q,MAO YQ,et al. Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum maxim. As a natural transdermal penetration enhancer[J]. J Zhejiang Univ Sci B,2014,15(2):153-164.
[27]单玲玲,靳光乾,王平,等.中药透皮吸收促进剂研究[J].辽宁中医药大学学报,2013,15(5):112-114.
[28]温亚,韩彬,戴王强,等.薄荷醇对芍药普透皮吸收作用的影响[J].湖南中医杂志,2014,30(5):128-130.
[29] DE SPIEQELEER B,BOONEN J,MALYSHEVA SV,et al.Skin penetration enhancing properties of the plant N-alkylamide spilanthol[J]. J Ethnopharm,2013,148(1):117-125.
[30]耿志霞,蒋春茂,刘腾飞,等.伊维菌素体外透皮吸收影响因素的研究[J].扬州大学学报,2013,34(2):20-24.
[31]李琳,杨晓艳,杨野,等.三七素体外经皮渗透特性研究[J].中草药,2015,46(17):2563-2567.
[32] BALAZS B,VIZSERALEK G,BERKO S,et al. Investigation of the efficacy of transdermal penetration enhancers through the use of human skin and a skin mimic artificial membrane[J]. J Pharm Sci,2016,105(3):1134-1140.
[33] CLARKE LL. A guide to ussing chamber studies of mouse intestine[J]. Am J Physiol Gastrointest Liver Physiol,2009,296(6):1151-1166.
[34]顾星,姚少姿,皮佳鑫,等.基于Ussing Chamber技术的红景天苷大鼠肠黏膜透过性研究[J].天津中医药,2016,33(11):689-693.
[35] ERDO F,HASHIMOTO N,KARVALY G,et al. Critical evaluation and methodological positioning of the transdermal microdialysis technique:a review[J]. J Control Release,2016,233:147-161.
[36]李得堂,吴晓贞,何嘉仑,等.在体皮肤微透析技术和HPLC测定吴茱萸碱和吴茱萸次碱的透皮释药特性[J].中国药学杂志,2015,50(3):239-243.
[37] XIE F,CHAI JK,HU Q,et al. Transdermal permeation of drugs with differing lipophilicity:effect of penetration enhancer camphor[J]. Int J Pharm,2016,507(1-2):90-101.
[38]戴居云,赵玲,王颖华,等.穴位透皮贴剂中丹参酮ⅡA的经皮吸收速率研究[J].现代中西医结合杂志,2004,13(24):3245-3248.
[39]李文华,王英姿,骆声秀,等.苦参总碱纳米乳和苦参总碱纳米乳凝胶的透皮机制研究[J].中草药,2017,48(3):484-489.
[40] VITORINO C,ALMEIDA A,SOUSA J,et al. Passive and active strategies for transdermal delivery using co-encapsulating nanostructured lipid carriers:in vitro vs in vivo studies[J]. Eur J Pharm Biopharm,2014,86(2):133-144.
[41] GOMAA YA,GARLAND MJ,MCINNES FJ,et al. Microneedle/nanoencapsulation-mediated transdermal delivery:mechanistic insights[J]. Eur J Pharm Biopharm,2014,86(2):145-155.
[42]梁震野,杨建苗,杜立峰,等.肉桂提取物醇质体凝胶经皮给药研究[J].中国现代应用药学,2013,30(11):1202-1206.
[43]王慧,张晓红,张燕,等.尼古丁乙醇脂质体的制备与体外透皮特性研究[J].中国药房,2015,26(19):2717-2720.
[44] THAKKAR PJ,MADAN P,LIN S. Transdermal delivery of diclofenac using water-in-oil microemulsion:formulation andmechanistic approach of drug skin permeation[J]. Pharm Dev Technol,2014,19(3):373-384.
[45]高玉红,庞淑华.微乳透皮给药机制及影响吸收的因素[J].饲料博览,2014,26(6):37-40.
[46]赵晶,金凯,宋光杰,等.水杨酸微乳的制备及其体外透皮吸收研究[J].中国药房,2015,26(1):112-114.
[47]章烨雯,王琼,于竞新,等.止痛微乳凝胶膏的制备及体外评价[J].北京中医药大学学报,2015,38(4):253-259.
[48] LADEMANN J,RICHTER H,MEINKE MC,et al. Drug delivery with topically applied nanoparticles:science fiction or reality[J]. Skin Pharmacol Physiol,2013,26(4-6):227-233.
[49] TACHAPRUTINUM A,MEINKE MC,RICHTER H,et al.Comparison of the skin penetration of Garcinia mangostana extract in particulate and non-particulate form[J]. Eur J Pharm Biop Harm,2014,88(2):307-313.
[50]肖志方.美洛昔康固体脂质纳米粒的制备及体外透皮研究[J].中国药师,2015,18(9):1512-1515.
[51]郭涤亮,徐萍蔚,王亚敏.皮肤局部外用仿制药质量等同性评价的一般考虑[J].中国新药杂志,2018,27(18):2116-2120.
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