驻极体5-氟尿嘧啶贴剂药物释放规律的线性回归分析
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摘要
目的:采用线性回归方法研究驻极体5-氟尿嘧啶(5-Fu)贴剂的药物释放规律。方法:利用驻极体实验技术与药剂学方法研制驻极体5-Fu贴剂,采用高效液相色谱仪检测驻极体5-Fu贴剂药物累积释放量,并对相关实验数据进行回归分析,从而将驻极体5-Fu贴剂药物释放规律模型化。结果:(1)驻极体可以为5-Fu贴剂提供稳恒静电场,该静电场大小与驻极体等效表面电位正相关。(2)驻极体5-Fu贴剂内静电场可改变贴剂黏性,从而实现对5-Fu药物释放量的调控;电场越强,贴剂黏性越小,贴剂累积释药量(Q)越大。(3)驻极体5-Fu贴剂的释药规律满足以下回归方程:V>0时,Q=(0.003V+13.47)t~(1/2)+0.136 6V~(1/2)+47.574;V=0时,Q=13.767t~(1/2)+48.052;V<0时,Q=(-0.003 8V+13.471)t~(1/2)+0.162 2(-V)~(1/2)+48.442。结论:驻极体静电场可对5-Fu贴剂释药量进行调节,其极性和等效表面电位是调控驻极体5-Fu贴剂释药速率的关键因素。
Objective To study the drug release rule in electret 5-fluorouracil(5-Fu) patch by linear regression method. Methods The electret 5-Fu patch was prepared by electret technology and pharmaceutical method, and the cumulative drug release from 5-Fu patch were detected by high-performance liquid chromatography. Regression analysis was performed on the test data to make it possible that the drug release rule in electret 5-Fu patch be modeled. Results Electret provided stable electrostatic field for 5-Fu patch, and the size of electrostatic field had positive correlations with the equivalent surface potentials of electret. The electrostatic field of electret 5-Fu patch effectively reduced the adhesion of patch, thus realizing the regulation of 5-Fu drug release. The smaller the adhesion of patch was, the higher the cumulative drug release(Q) from patch was. The drug release rule of electret 5-Fu patch accorded with the followed regression equations: V>0, Q=(0.003 V+13.47)t~(1/2)+0.136 6 V~(1/2)+47.574; V=0, Q=13.767 t~(1/2)+48.052; V<0, Q=(-0.003 8 V+13.471) t~(1/2)+0.162 2(-V)~(1/2)+48.442. Conclusion The electrostatic field of electret can regulate the release velocity of drug from 5-Fu patch and the polarity and equivalent surface potential of electret are the key influence factors for the regulation.
Objective To study the drug release rule in electret 5-fluorouracil(5-Fu) patch by linear regression method. Methods The electret 5-Fu patch was prepared by electret technology and pharmaceutical method, and the cumulative drug release from 5-Fu patch were detected by high-performance liquid chromatography. Regression analysis was performed on the test data to make it possible that the drug release rule in electret 5-Fu patch be modeled. Results Electret provided stable electrostatic field for 5-Fu patch, and the size of electrostatic field had positive correlations with the equivalent surface potentials of electret. The electrostatic field of electret 5-Fu patch effectively reduced the adhesion of patch, thus realizing the regulation of 5-Fu drug release. The smaller the adhesion of patch was, the higher the cumulative drug release(Q) from patch was. The drug release rule of electret 5-Fu patch accorded with the followed regression equations: V>0, Q=(0.003 V+13.47)t~(1/2)+0.136 6 V~(1/2)+47.574; V=0, Q=13.767 t~(1/2)+48.052; V<0, Q=(-0.003 8 V+13.471) t~(1/2)+0.162 2(-V)~(1/2)+48.442. Conclusion The electrostatic field of electret can regulate the release velocity of drug from 5-Fu patch and the polarity and equivalent surface potential of electret are the key influence factors for the regulation.
引文
[1]孔德平,陈凯.5-氟尿嘧啶对增生性瘢痕的作用研究[J].重庆医学,2015,44(8):1029-1031.KONG D P,CHEN K.The effects of 5-fluorouracil on hypertrophic scar of rabbit ears[J].Chongqing Medicine,2015,44(8):1029-1031.
[2]APIKIAN M,GOODMAN G.Intralesional 5-fluorouracil in the treatment of keloid scars[J].Australas J Dermatol,2015,45(2):140-143.
[3]KABEL A M,SABRY H H,SOROUR N E,et al.Comparative study between intralesional injection of bleomycin and 5-fluorouracil in the treatment of keloids and hypertrophic scars[J].J Dermatol Dermatol Surg,2016,20(1):32-38.
[4]徐立丽,黄平,苑旺,等.正极性聚丙烯驻极体外静电场对5-氟尿嘧啶贴剂中药物释放的影响[J].高电压技术,2017,43(6):1925-1929.XU L L,HUANG P,YUAN W,et al.Effect of external electrostatic field of positive PP electrets on release of 5-fluorouracil from adhesive patch[J].High Voltage Engineering,2017,43(6):1925-1929.
[5]郭鑫,崔黎丽,梁媛媛,等.负极性驻极体环孢菌素A贴剂的压电特性[J].高电压技术,2014,40(6):1916-1920.GUO X,CUI L L,LIANG Y Y,et al.Piezoelectric properties of negative electret cyclosporine A patch[J].High Voltage Engineering,2014,40(6):1916-1920.
[6]江键,梁媛媛,崔黎丽,等.静电场对大鼠皮肤角质层结构的调控[J].河北大学学报(自然科学版),2007,27(6):606-609.JIANG J,LIANG Y Y,CUI L L,et al.Regulation effect of electrostatic field on stratum corneum of rat skin[J].Journal of Hebei University(Natural Science Edition),2007,27(6):606-609.
[7]梁媛媛,董法杰,马琳,等.驻极体对大鼠皮肤显微结构影响的时间效应研究[J].广东工业大学学报,2011,28(2):88-90.LIANG Y Y,DONG F J,MA L,et al.A study of the time effect of the influence of electret on rat skin structure[J].Journal of Guangdong University of Technology,2011,28(2):88-90.
[8]梁媛媛,王美玲,崔黎丽,等.驻极体产生的静电场与胰岛素的相互作用及其药效学初探[J].高电压技术,2014,40(6):1909-1915.LIANG Y Y,WANG M L,CUI L L,et al.Interaction between electrostatic field generated by electret with insulin and its pharmacodynamics exploration[J].High Voltage Engineering,2014,40(6):1909-1915.
[9]黄平,石岩,郭鑫,等.正极性驻极体环孢菌素A贴剂的开路热刺激放电[J].高电压技术,2015,41(4):1390-1394.HUANG P,SHI Y,GUO X,et al.Open thermally stimulated discharge of positive electret cyclosporine A patch[J].High Voltage Engineering,2015,41(4):1390-1394.
[10]包家立.极低频电磁场的健康效应[J].高电压技术,2015,41(8):2550-2561.BAO J L.Health effects of extremely low frequency electromagnetic fileds[J].High Voltage Engineering,2015,41(8):2550-2561.
[11]曲敏,毕卓悦,唐雨萌,等.生物电磁技术应用及其相关健康风险评估对策[J].高电压技术,2015,41(8):2625-2634.QU M,BI Z Y,TANG Y M,et al.Application of bio-electromagnetic technique and its related health risk assessment strategy[J].High Voltage Engineering,2015,41(8):2625-2634.
[12]GB/T 4851-1988中国标准书号[S].北京:中国标准出版社,1988.GB/T 4851-1988 China ISBN[S].Beijing:Standards Press of China,1988.
[13]周卫新,袁永健,石俭莉,等.压敏胶黏剂的研究进展[J].化工新型材料,2009,37(9):37-43.ZHOU W X,YUAN Y J,SHI J L,et al.Research progress of pressure sensitive adhesives[J].New Chemical Materials,2009,37(9):37-43.
[14]刘鸿越,江键,马琳,等.驻极体及联用氮酮对环孢菌素A的体外透皮促渗作用[J].药学实践,2012,30(6):440-442.LIU H Y,JIANG J,MA L,et al.Penetration enhancement of electret and united azone on cyclosporin A transdermal delivery in vitro[J].Journal of Pharmaceutical Practice,2012,30(6):440-442.
[15]陈力,刘砚韬,黄亮,等.缓控释系统药物释放的数学模型研究进展[J].中国药业,2008,17(11):1-4.CHEN L,LIU Y T,HUANG L,et al.Research progress of mathematic model of sustained and controlled release system of drug release[J].China Pharmaceuticals,2008,17(11):1-4.
[16]MURTHY N S,BOGUDA V A,PAYASADA K.Electret enhances transdermal drug permeation[J].Biol Pharm Bull,2008,31(1):99-102.
[17]徐立丽,苑旺,梁媛媛,等.负极性驻极体静电场对5-氟尿嘧啶贴剂体外释放规律的影响[J].第二军医大学学报,2017,38(3):294-299.XU L L,YUAN W,LIANG Y Y,et al.Effect of electrostatic field of negative polarity eletret on in vitro release behavior of 5-fluorouracil patch[J].Academic Journal of Second Military University,2017,38(3):294-299.
[18]董岸杰,张睿,张建华,等.共聚物压敏胶的链段结构对其力学性能和药物释放的调控[J].天津大学学报,2012,45(11):1011-1019.DONG A J,ZHANG R,ZHANG J H,et al.Effect of segment structure on mechanical properties and drug release behavior of copolymer pressure sensitive adhesives[J].Journal of Tianjin University,2012,45(11):1011-1019.
[19]WOKOVICH A M,PRODDUTURI S,DOUB W H,et al.Transdermal drug delivery system(TDDS)adhesion a critical safety,efficacy and quality attribute[J].Eur J Pharm Biopharm,2006,64(1):1-8.
[2]APIKIAN M,GOODMAN G.Intralesional 5-fluorouracil in the treatment of keloid scars[J].Australas J Dermatol,2015,45(2):140-143.
[3]KABEL A M,SABRY H H,SOROUR N E,et al.Comparative study between intralesional injection of bleomycin and 5-fluorouracil in the treatment of keloids and hypertrophic scars[J].J Dermatol Dermatol Surg,2016,20(1):32-38.
[4]徐立丽,黄平,苑旺,等.正极性聚丙烯驻极体外静电场对5-氟尿嘧啶贴剂中药物释放的影响[J].高电压技术,2017,43(6):1925-1929.XU L L,HUANG P,YUAN W,et al.Effect of external electrostatic field of positive PP electrets on release of 5-fluorouracil from adhesive patch[J].High Voltage Engineering,2017,43(6):1925-1929.
[5]郭鑫,崔黎丽,梁媛媛,等.负极性驻极体环孢菌素A贴剂的压电特性[J].高电压技术,2014,40(6):1916-1920.GUO X,CUI L L,LIANG Y Y,et al.Piezoelectric properties of negative electret cyclosporine A patch[J].High Voltage Engineering,2014,40(6):1916-1920.
[6]江键,梁媛媛,崔黎丽,等.静电场对大鼠皮肤角质层结构的调控[J].河北大学学报(自然科学版),2007,27(6):606-609.JIANG J,LIANG Y Y,CUI L L,et al.Regulation effect of electrostatic field on stratum corneum of rat skin[J].Journal of Hebei University(Natural Science Edition),2007,27(6):606-609.
[7]梁媛媛,董法杰,马琳,等.驻极体对大鼠皮肤显微结构影响的时间效应研究[J].广东工业大学学报,2011,28(2):88-90.LIANG Y Y,DONG F J,MA L,et al.A study of the time effect of the influence of electret on rat skin structure[J].Journal of Guangdong University of Technology,2011,28(2):88-90.
[8]梁媛媛,王美玲,崔黎丽,等.驻极体产生的静电场与胰岛素的相互作用及其药效学初探[J].高电压技术,2014,40(6):1909-1915.LIANG Y Y,WANG M L,CUI L L,et al.Interaction between electrostatic field generated by electret with insulin and its pharmacodynamics exploration[J].High Voltage Engineering,2014,40(6):1909-1915.
[9]黄平,石岩,郭鑫,等.正极性驻极体环孢菌素A贴剂的开路热刺激放电[J].高电压技术,2015,41(4):1390-1394.HUANG P,SHI Y,GUO X,et al.Open thermally stimulated discharge of positive electret cyclosporine A patch[J].High Voltage Engineering,2015,41(4):1390-1394.
[10]包家立.极低频电磁场的健康效应[J].高电压技术,2015,41(8):2550-2561.BAO J L.Health effects of extremely low frequency electromagnetic fileds[J].High Voltage Engineering,2015,41(8):2550-2561.
[11]曲敏,毕卓悦,唐雨萌,等.生物电磁技术应用及其相关健康风险评估对策[J].高电压技术,2015,41(8):2625-2634.QU M,BI Z Y,TANG Y M,et al.Application of bio-electromagnetic technique and its related health risk assessment strategy[J].High Voltage Engineering,2015,41(8):2625-2634.
[12]GB/T 4851-1988中国标准书号[S].北京:中国标准出版社,1988.GB/T 4851-1988 China ISBN[S].Beijing:Standards Press of China,1988.
[13]周卫新,袁永健,石俭莉,等.压敏胶黏剂的研究进展[J].化工新型材料,2009,37(9):37-43.ZHOU W X,YUAN Y J,SHI J L,et al.Research progress of pressure sensitive adhesives[J].New Chemical Materials,2009,37(9):37-43.
[14]刘鸿越,江键,马琳,等.驻极体及联用氮酮对环孢菌素A的体外透皮促渗作用[J].药学实践,2012,30(6):440-442.LIU H Y,JIANG J,MA L,et al.Penetration enhancement of electret and united azone on cyclosporin A transdermal delivery in vitro[J].Journal of Pharmaceutical Practice,2012,30(6):440-442.
[15]陈力,刘砚韬,黄亮,等.缓控释系统药物释放的数学模型研究进展[J].中国药业,2008,17(11):1-4.CHEN L,LIU Y T,HUANG L,et al.Research progress of mathematic model of sustained and controlled release system of drug release[J].China Pharmaceuticals,2008,17(11):1-4.
[16]MURTHY N S,BOGUDA V A,PAYASADA K.Electret enhances transdermal drug permeation[J].Biol Pharm Bull,2008,31(1):99-102.
[17]徐立丽,苑旺,梁媛媛,等.负极性驻极体静电场对5-氟尿嘧啶贴剂体外释放规律的影响[J].第二军医大学学报,2017,38(3):294-299.XU L L,YUAN W,LIANG Y Y,et al.Effect of electrostatic field of negative polarity eletret on in vitro release behavior of 5-fluorouracil patch[J].Academic Journal of Second Military University,2017,38(3):294-299.
[18]董岸杰,张睿,张建华,等.共聚物压敏胶的链段结构对其力学性能和药物释放的调控[J].天津大学学报,2012,45(11):1011-1019.DONG A J,ZHANG R,ZHANG J H,et al.Effect of segment structure on mechanical properties and drug release behavior of copolymer pressure sensitive adhesives[J].Journal of Tianjin University,2012,45(11):1011-1019.
[19]WOKOVICH A M,PRODDUTURI S,DOUB W H,et al.Transdermal drug delivery system(TDDS)adhesion a critical safety,efficacy and quality attribute[J].Eur J Pharm Biopharm,2006,64(1):1-8.