肉桂油对马钱子总碱中马钱子碱和士的宁透皮吸收的影响
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摘要
目的探讨肉桂油对马钱子总碱透皮吸收的影响,为马钱子相关制剂的开发和减毒增效研究奠定基础。方法以体外SD大鼠皮肤为渗透屏障,Franz扩散池法考察不同浓度(0.5%、1%、3%、5%、10%)肉桂油对马钱子总碱中马钱子碱和士的宁透皮吸收的影响;采用饱和溶解度法测定马钱子总碱中马钱子碱和士的宁在不同浓度肉桂油中的平衡溶解度;采用HPLC测定马钱子总碱角质层/溶剂分配系数;采用傅里叶变换衰减全反射红外光谱技术测定肉桂油对皮肤角质层的作用。结果不同浓度肉桂油促透马钱子总碱中马钱子碱的稳态渗透速率(Jss)和增渗比(ER)分别为5.84~19.65μg/(cm~2·h)、0.23~3.54,促透马钱子总碱中士的宁的Jss和ER分别为1.36~18.38μg/(cm~2·h)、0.19~2.55;马钱子总碱中马钱子碱、士的宁在不同浓度肉桂油中的平衡溶解度分别为6.10~10.97 g/L、4.10~6.58 g/L;马钱子总碱中马钱子碱和士的宁的角质层/溶剂分配系数分别为0.74~1.39、0.24~0.35。结论不同浓度肉桂油对马钱子总碱中的马钱子碱及士的宁均有一定促透作用,以1%肉桂油作用最佳,其机制可能为通过影响角质层内角蛋白改变角质层结构而促透。
Objective To investigate the effects of cinnamon oil on the transdermal absorption of total alkaloids from Strychni Semen; To establish an foundation for the development of related preparations of Strychni Semen and its attenuated and synergistic effects. Methods The SD rat skin was used as a permeation barrier in vitro. The effects of different concentrations of cinnamon oil(0.5%, 1%, 3%, 5%, 10%) on transdermal absorption of brucine and strychnine in total alkaloids from Strychni Semen were investigated by Franz diffusion pool method. The equilibrium solubility of brucine and strychnine of total alkaloids from Strychni Semen in different concentrations of cinnamon oil was determined by saturated solubility method. The stratum corneum/solvent partition coefficient of total alkaloids from Strychni Semen was determined by HPLC. ATR-FTIR technique was used to determine the effects of cinnamon oil on the stratum corneum of skin. Results The steady-state rate of permeation(Jss) and enhancement ratio(ER) of brucine of total alkaloids from Strychni Semen were 5.84–19.65 μg/(cm~2·h) and 0.23–3.54, respectively; strychnine's Jss and ER were 1.36–18.38 μg/(cm~2·h) and 0.19–2.55, respectively. The equilibrium solubility of brucine and strychnine in total alkaloids in different concentrations of cinnamon oil was 6.10–10.97 g/L and 4.10–6.58 g/L. The stratum corneum/solvent partition coefficient of brucine and strychnine were 0.74–1.39 and 0.24–0.35, respectively. Conclusion Different concentrations of cinnamon oil can promote penetration of brucine and strychnine in Strychni Semen, and with 1% cinnamon oil the best. The penetration promoting mechanism of cinnamon oil may promote the penetration by influencing the keratin to change the structure of stratum corneum.
Objective To investigate the effects of cinnamon oil on the transdermal absorption of total alkaloids from Strychni Semen; To establish an foundation for the development of related preparations of Strychni Semen and its attenuated and synergistic effects. Methods The SD rat skin was used as a permeation barrier in vitro. The effects of different concentrations of cinnamon oil(0.5%, 1%, 3%, 5%, 10%) on transdermal absorption of brucine and strychnine in total alkaloids from Strychni Semen were investigated by Franz diffusion pool method. The equilibrium solubility of brucine and strychnine of total alkaloids from Strychni Semen in different concentrations of cinnamon oil was determined by saturated solubility method. The stratum corneum/solvent partition coefficient of total alkaloids from Strychni Semen was determined by HPLC. ATR-FTIR technique was used to determine the effects of cinnamon oil on the stratum corneum of skin. Results The steady-state rate of permeation(Jss) and enhancement ratio(ER) of brucine of total alkaloids from Strychni Semen were 5.84–19.65 μg/(cm~2·h) and 0.23–3.54, respectively; strychnine's Jss and ER were 1.36–18.38 μg/(cm~2·h) and 0.19–2.55, respectively. The equilibrium solubility of brucine and strychnine in total alkaloids in different concentrations of cinnamon oil was 6.10–10.97 g/L and 4.10–6.58 g/L. The stratum corneum/solvent partition coefficient of brucine and strychnine were 0.74–1.39 and 0.24–0.35, respectively. Conclusion Different concentrations of cinnamon oil can promote penetration of brucine and strychnine in Strychni Semen, and with 1% cinnamon oil the best. The penetration promoting mechanism of cinnamon oil may promote the penetration by influencing the keratin to change the structure of stratum corneum.
引文
[1]董建军,郗淑娟,张桂锋.制马钱子的临床应用[J].中国现代药物应用,2016,10(16):277-279.
[2]韩进庭.马钱子的药理作用和临床应用[J].现代医药卫生,2007,23(17):2622-2623.
[3]YIN W,WANG T S,YIN F Z,et al.Analgesic and anti-inflammatory properties of brucine and brucine N-oxide extracted from seeds of Strychnos nux-vomica[J].J Ethnopharmacol,2003,88(3):205-214.
[4]周建英,卞慧敏,马骋,等.马钱子碱和马钱子碱氮氧化物抗血小板聚集及抗血栓形成作用的研究[J].江苏中医,1998,19(4):41-43.
[5]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,2015:402.
[6]李朝阳,娄玉钤,苗根旺,等.配伍肉桂、桂枝对马钱子毒性影响的实验研究[J].风湿病与关节炎,2012,1(6):28-30.
[7]闫静,朱海光,刘志强,等.马钱子与甘草配伍前后生物碱成分的变化规律[J].分析化学,2007,35(8):1218-1220.
[8]闫雪生,朱建伟,江波,等.马钱子与肉桂配伍前后士的宁和马钱子碱的分析[J].中国实验方剂学杂志,2010,16(6):77-78.
[9]王晓崴,刘兆华,龚千锋,等.人工肠胃条件下马钱子与肉桂配伍前后有效成分含量的变化[C]//2013全国中药与天然药物高峰论坛论文集,2013:106.
[10]王艳宏,齐笑,关枫,等.马钱子总碱中2种成分的平衡溶解度、油水分配系数、体外透皮特性[J].中成药,2017,39(10):2034-2038.
[11]CHEN J,JIANG Q D,WU Y M,et al.Potential of essential oils as penetration enhancers for transdermal administration of ibuprofen to treat dysmenorrhoea[J].Molecules,2015,20(10):18219-18236.
[12]张定,王承潇,杨晓艳,等.促渗剂对三七中人参皂苷Rh1体外透皮的影响[J].中成药,2015,37(3):511-517.
[13]LAN Y,QING W U,MAO Y Q,et al.Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum Maxim.as a natural transdermal penetration enhancer[J].Journal of Zhejiang University Science B,2014,15(2):153-164.
[14]LAN Y,WU Q,MAO Y Q,et al.Essential oil from Zanthoxylum bungeanum Maxim.and its main components used as transdermal penetration enhancers:a comparative study[J].Journal of Zhejiang University Science B,2014,15(11):940-952.
[15]ZHANG C F,YANG Z L,LUO J B,et al.Effects of cinnamene enhancers on transdermal delivery of ligustrazine hydrochloride[J].European Journal of Pharmaceutics&Biopharmaceutics,2007,67(2):413.
[16]MOORE D J,REREK M E.Insight into the molecular organization of lipids in the skin barrier from infrared spectroscopy studies of stratum corneum lipid models[J].Acta Derm Venereol Supp,2000,208:16-22.
[17]JAIN A K,THOMAS N S,PANCHAGNULA R.Transdermal drug delivery of imipramine hydrochloride.:I.Effect of terpenes[J].Journal of Controlled Release,2002,79(1):93-101.
[18]KHURANA S,JAIN N K,BEDI P M.Nanoemulsion based gel for transdermal delivery of meloxicam:physico-chemical,mechanistic investigation[J].Life Sciences,2013,92(6/7):383-392.
[19]ZBYTOVSKáJ,RAUDENKOLB S,WARTEWIG S,et al.Phase behaviour of transkarbam 12[J].Chemistry&Physics of Lipids,2004,129(1):97-109.
[20]郑俊民.经皮给药新剂型[M].北京:人民卫生出版社,2006:434-442.
[21]PANCHAGNULA R,SALVE P S,THOMAS N S,et al.Transdermal delivery of naloxone:effect of water,propylene glycol,ethanol and their binary combinations on permeation through rat skin[J].International Journal of Pharmaceutics,2001,219(1):95-105.
[22]BATHEJA P,SHEIHET L,KOHN J,et al.Topical drug delivery by a polymeric nanosphere gel:Formulation optimization and in vitro,and in vivo,skin distribution studies[J].Journal of Controlled Release,2011,149(2):159-167.
[23]兰颐,王琼,安静,等.不同接受液对药物体外透皮试验的影响[J].中国实验方剂学杂志,2013,19(13):7-10.
[24]沈琦,胡晋红,徐莲英.肉桂等3种挥发油对苯甲酸透皮吸收的影响[J].中国医院药学杂志,2001,21(4):197-199.
[25]周晓伟.香附挥发油对苯二氮类药物促透皮作用研究[D].西安:第四军医大学,2012.
[26]ZHANG L C,HU J H,LI L,et al.In vivo and in vitro evaluation of essential oils from Ligusticum chuanxiong Hort on the transdermal delivery of flurbiprofen in rabbits[J].Biological&Pharmaceutical Bulletin,2006,29(6):1217-1222.
[2]韩进庭.马钱子的药理作用和临床应用[J].现代医药卫生,2007,23(17):2622-2623.
[3]YIN W,WANG T S,YIN F Z,et al.Analgesic and anti-inflammatory properties of brucine and brucine N-oxide extracted from seeds of Strychnos nux-vomica[J].J Ethnopharmacol,2003,88(3):205-214.
[4]周建英,卞慧敏,马骋,等.马钱子碱和马钱子碱氮氧化物抗血小板聚集及抗血栓形成作用的研究[J].江苏中医,1998,19(4):41-43.
[5]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,2015:402.
[6]李朝阳,娄玉钤,苗根旺,等.配伍肉桂、桂枝对马钱子毒性影响的实验研究[J].风湿病与关节炎,2012,1(6):28-30.
[7]闫静,朱海光,刘志强,等.马钱子与甘草配伍前后生物碱成分的变化规律[J].分析化学,2007,35(8):1218-1220.
[8]闫雪生,朱建伟,江波,等.马钱子与肉桂配伍前后士的宁和马钱子碱的分析[J].中国实验方剂学杂志,2010,16(6):77-78.
[9]王晓崴,刘兆华,龚千锋,等.人工肠胃条件下马钱子与肉桂配伍前后有效成分含量的变化[C]//2013全国中药与天然药物高峰论坛论文集,2013:106.
[10]王艳宏,齐笑,关枫,等.马钱子总碱中2种成分的平衡溶解度、油水分配系数、体外透皮特性[J].中成药,2017,39(10):2034-2038.
[11]CHEN J,JIANG Q D,WU Y M,et al.Potential of essential oils as penetration enhancers for transdermal administration of ibuprofen to treat dysmenorrhoea[J].Molecules,2015,20(10):18219-18236.
[12]张定,王承潇,杨晓艳,等.促渗剂对三七中人参皂苷Rh1体外透皮的影响[J].中成药,2015,37(3):511-517.
[13]LAN Y,QING W U,MAO Y Q,et al.Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum Maxim.as a natural transdermal penetration enhancer[J].Journal of Zhejiang University Science B,2014,15(2):153-164.
[14]LAN Y,WU Q,MAO Y Q,et al.Essential oil from Zanthoxylum bungeanum Maxim.and its main components used as transdermal penetration enhancers:a comparative study[J].Journal of Zhejiang University Science B,2014,15(11):940-952.
[15]ZHANG C F,YANG Z L,LUO J B,et al.Effects of cinnamene enhancers on transdermal delivery of ligustrazine hydrochloride[J].European Journal of Pharmaceutics&Biopharmaceutics,2007,67(2):413.
[16]MOORE D J,REREK M E.Insight into the molecular organization of lipids in the skin barrier from infrared spectroscopy studies of stratum corneum lipid models[J].Acta Derm Venereol Supp,2000,208:16-22.
[17]JAIN A K,THOMAS N S,PANCHAGNULA R.Transdermal drug delivery of imipramine hydrochloride.:I.Effect of terpenes[J].Journal of Controlled Release,2002,79(1):93-101.
[18]KHURANA S,JAIN N K,BEDI P M.Nanoemulsion based gel for transdermal delivery of meloxicam:physico-chemical,mechanistic investigation[J].Life Sciences,2013,92(6/7):383-392.
[19]ZBYTOVSKáJ,RAUDENKOLB S,WARTEWIG S,et al.Phase behaviour of transkarbam 12[J].Chemistry&Physics of Lipids,2004,129(1):97-109.
[20]郑俊民.经皮给药新剂型[M].北京:人民卫生出版社,2006:434-442.
[21]PANCHAGNULA R,SALVE P S,THOMAS N S,et al.Transdermal delivery of naloxone:effect of water,propylene glycol,ethanol and their binary combinations on permeation through rat skin[J].International Journal of Pharmaceutics,2001,219(1):95-105.
[22]BATHEJA P,SHEIHET L,KOHN J,et al.Topical drug delivery by a polymeric nanosphere gel:Formulation optimization and in vitro,and in vivo,skin distribution studies[J].Journal of Controlled Release,2011,149(2):159-167.
[23]兰颐,王琼,安静,等.不同接受液对药物体外透皮试验的影响[J].中国实验方剂学杂志,2013,19(13):7-10.
[24]沈琦,胡晋红,徐莲英.肉桂等3种挥发油对苯甲酸透皮吸收的影响[J].中国医院药学杂志,2001,21(4):197-199.
[25]周晓伟.香附挥发油对苯二氮类药物促透皮作用研究[D].西安:第四军医大学,2012.
[26]ZHANG L C,HU J H,LI L,et al.In vivo and in vitro evaluation of essential oils from Ligusticum chuanxiong Hort on the transdermal delivery of flurbiprofen in rabbits[J].Biological&Pharmaceutical Bulletin,2006,29(6):1217-1222.