复方盐酸萘替芬乳膏对离体豚鼠皮肤的透皮吸收研究

目的:研究复方盐酸萘替芬乳膏对离体豚鼠皮肤的透皮作用及皮肤组织中的药物浓度。方法:采用静态渗透室装置,皮片涂不同浓度盐酸萘替芬、酮康唑单一及复方乳膏制剂(盐酸萘替芬1%、2%、4%,酮康唑0.25%、0.5%、1%)后36h内不同时间(6、12、24、36h)取样,采用高效液相色谱法测定样品中及皮肤组织中盐酸萘替芬、酮康唑浓度。结果:盐酸萘替芬、酮康唑经离体豚鼠皮的透过率随时间的延长而缓慢增加。36h时,高浓度复方制剂中盐酸萘替芬、酮康唑经离体豚鼠皮的平均透过率分别为(9.3±8.6)×10-3%、(1.39±0.20)%;豚鼠皮中二者浓度分别为(29.81±12.16)、(60.76±5.47)μg.g-1。结论:复方盐酸萘替芬乳膏局部皮肤给药36h后,药物在皮肤组织中浓度较高,表明其透过皮肤吸收较少。     

薄荷脑和樟脑对复方苯海拉明乳膏透皮作用的影响

目的研究薄荷脑和樟脑对复方苯海拉明乳膏中盐酸苯海拉明和苯佐卡因透皮作用的影响。方法采用改良Franz直立式扩散池,以离体乳猪皮肤为渗透屏障进行体外透皮扩散试验,以盐酸苯海拉明和苯佐卡因的累积渗透量、稳态流量及皮肤滞留量为指标,考察薄荷脑和樟脑在处方中的透皮调节作用。结果薄荷脑和樟脑对盐酸苯海拉明的累积渗透量、稳态流量及皮肤滞留量均无显著影响(P>0.05);对苯佐卡因的累积渗透量、稳态流量有显著抑制作用(P<0.01),并能提高其12 h皮肤滞留量(P<0.05)。结论薄荷脑和樟脑在复方苯海拉明乳膏中除发挥其药理活性外,还能调节药物的透皮吸收,其对苯佐卡因经皮渗透的抑制及皮肤滞留量的增加可能更有利于复方苯海拉明乳膏发挥局部治疗作用。     

复方布替萘芬乳膏在家兔体内的药动学研究

目的探索家兔外用复方布替萘芬乳膏的体内药动学评价方法。方法 6只家兔给予3 g复方布替萘芬乳膏,采用LC-MS/MS法同时测定家兔血浆中的布替萘芬和糠酸莫米松浓度。结果以LC-MS/MS法监测外用复方布替萘芬乳膏主要成分布替萘芬和糠酸莫米松通过皮肤吸收进入血液的药动学参数,布替萘芬Cmax为（16.16±7.15）ng/mL、Tmax为（10.5±7.3）h、AUC（0 T）为（131.1±51.07）ng h mL-1;糠酸莫米松Cmax为（0.707±0.439）ng/mL,Tmax为（6.7±8.7）h,AUC（0 T）为（2.891±1.368）ng h mL-1。结论外用乳膏同样可以药动学参数评估临床用药的安全性。本试验建立的LC-MS/MS同时测定血浆中布替萘芬和糠酸莫米松的方法,灵敏度高,符合透皮给药药动学研究要求。     

盐酸特比萘芬乳膏的透皮吸收和含量测定

目的:建立盐酸特比萘芬乳膏HPLC分析方法,并使用该方法进行自制乳膏和原研制剂的透皮吸收考察和自制乳膏的含量测定.方法:采用Kromasil C₁₈柱(4.6 mm×250 mm,5 μm),甲醇-乙腈-pH 7.5的醋酸三乙胺缓冲液(55:35:10)为流动相,流速1 ml·min^-1,检测波长282 nm.体外透皮实验采用Franz智能透皮吸收仪,以实验用离体乳猪皮为透皮屏障,通过累计渗透量和皮肤滞留量评价自制乳膏与原研制剂的透皮相似性.结果:盐酸特比萘芬质量浓度在4~150 ng·ml^-1、20~400 μg·ml^-1范围内线性关系良好(r=0.999 6,r=0.999 8),盐酸特比萘芬溶液平均回收率为98.88%,制剂加样平均回收率为100.4%.3批自制乳膏的平均含量为97.2%,累计渗透量和24 h皮肤滞留量与原研制剂差异无显著性(P >0.05).结论:所建立HPLC方法快速、准确,可同时用于盐酸特比萘芬乳膏的透皮吸收考察和含量测定.自制乳膏的透皮吸收特性与原研制剂相似,含量达到要求.     

1%布替萘芬乳膏治疗浅部真菌病疗效观察

目的：观察1％盐酸布替茶芬乳膏（嘉瑞）治疗浅部真菌病临床疗效和安全性。方法：1％盐酸布替萘芬乳膏qd连续2周和4周，分别治疗经临床和真菌学检查证实的体股癣、汗斑和手足癣（角化型除外），在第6周时全面评价临床疗效、真菌清除率和安全性。结果：1％盐酸布替萘芬乳膏治疗体股癣、汗斑、手足癣患者的临床治愈率98．13％，真菌清除率95．32％。结论：1％盐酸布替萘芬乳膏为疗效高、安全性好的抗真菌药。     

盐酸布替萘芬乳膏治疗浅部真菌病的疗效观察

目的 :探讨盐酸布替萘芬乳膏治疗浅部真菌病的疗效和安全性。方法 :采用随机、对照的临床研究方法 ,对 6 0例浅部真菌病患者进行分组 ,试验组以盐酸布替萘芬乳膏外用 ,对照组采用特比萘芬乳膏外用 ,观察用药 3周的临床疗效。结果 :用药后 3周试验组和对照组的有效率分别为 83.33%和 80 .0 0 %。试验组略高于对照组 ,但差异无显著性。结论 :盐酸布替萘芬乳膏治疗浅部真菌病快速、安全、有效。     

复方盐酸布替萘芬乳膏剂的制备及其含量测定

目的制备复方盐酸布替萘芬乳膏剂。方法分别应用高效液相色谱法和分光光度法测定盐酸布替萘芬和尿素的含量。结果两种方法含量测定的平均回收率为99.92%和99.87%,RSD分别为0.49%和0.32%。结论所制复方盐酸布替萘芬乳膏剂的质量符合规定。     

曲安奈德益康唑乳膏的透皮吸收实验

摘要：目的:建立曲安奈德益康唑乳膏体外透皮扩散实验方法,测定并评价不同厂家产品的体外透皮能力。方法:采用立式改良Franz扩散池及乳猪离体皮肤对11个厂家的产品进行体外透皮扩散试验,以HPLC法测定接受液中曲安奈德与硝酸益康唑的含量和皮肤中的贮留量。结果:2个厂家产品与原研厂家产品中曲安奈德和益康唑的体外透皮吸收情况差异无统计学意义,其余厂家产品与原研相比透皮吸收情况有一定差异。结论:新建方法适用于曲安奈德益康唑乳膏的体外透皮吸收测定,为其质量评价提供了依据。     

布替萘芬对豚鼠皮肤须发癣霉的疗效观察

目的：观察布替萘芬乳膏剂治疗豚鼠皮肤真菌病的疗效。方法：本实验共建立皮肤真菌病豚鼠感染模型４５处,分别是１％布替藉芬治疗组,１％萘替芬乳膏治疗组,１％联苯苄唑乳膏治疗组,１％克霉唑软膏治疗组和空白对照组和空白,疗程为１４天,药物治疗结束后观察复发状况。结果：布替萘芬乳膏１０天临床治愈率比联苯苄唑乳膏和萘替分乳膏高２２．３％,但无显著性差异（Ｐ〉０．０５）,与克霉唑软膏差异有显著性意义（Ｐ〈０．０５     

氮酮和薄荷醇对特比萘芬体外经皮渗透性的影响

目的 研究透皮促进剂氮酮和薄荷醇对外用抗真菌药特比萘芬体外经皮渗透性的影响。方法 在离体透皮实验装置上进行透皮吸收试验和贮库效应的研究，采用正交函数分光光度法消除皮肤浸出物的吸收干扰。结果 1％氮酮和1％薄荷醇对特比萘芬经皮渗透有明显促进作用，且两者合用可明显缩短时滞。结 论薄荷醇和氮酮对特比蔡芬体外经皮吸收具有显著的促进作用，并能增加贮库效应。     

含薄荷醇的复合促透剂促进盐酸氯丙嗪经皮吸收

目的：用含薄荷醇的复合促透剂对盐酸氯嗪透皮吸收作一探讨。方法：采用正交试验方法,在离体透皮实验装置上进行透皮试验的最佳处方筛选和确定,并用小鼠进行镇静试验。结果：发现2％的薄荷醇、4％的氮酮、5％的丙二醇及60％的乙醇（浓度为75％）组成的复合促透剂对盐酸氯丙嗪的体外透皮吸收具有显著的促进作用,由此组成的盐酸氯丙嗪透皮液外涂小鼠皮肤后可产生明显的镇静作用。结论：含薄荷醇的复合促透剂对盐酸氯丙嗪透皮吸收具有促进作用。     

Comparative percutaneous absorption of pyrithiones.

The percutaneous absorption of 3H or 35S labelled pyridine-2-thione-N-oxide (PT) through the skin of rat, rabbit and guinea pigs in vivo is reported. The sodium (Na) zinc (Zn) and zirconium (Zr) derivatives of PT were studied and the effects of duration of contact and concentration of the NaPT and ZnPT in test solutions were examined. Shampoo test solutions containing the isotopically labelled PT were applied to the skin of the animals. The skins were then rinsed, the treated areas of skin protected and excreta were monitored for the isotope for 2 days after treatment. Penetration was calculated from the amounts of isotope in the excreta. Further groups of animals were treated with test solutions applied under occlusive patches for 6 h before rinsing the skin. The turnover of Na and ZnPT in the three species after intraperitoneal and subcutaneous injection was measured. All three species rapidly excreted the injected isotope principally via the urine. The comparative penetration of the three PT samples was Na greater than Zr greater than Zn from all treatments. The comparative permeability of the animals' skins to these PTs was rabbit greater than rat greater than guinea pig. NaPT penetration was found to be dependent upon duration of contact and concentration in the test solution whereas the penetration of ZnPT was found to be proportional to concentration but independent of duration of contact of the test solution. Extrapolation of these findings to the use of shampoos containing up to 1% (w/v) ZnPT by man indicated an adequate margin of safety for use of this type of product.     

Butenafine and superficial mycoses: current status

BACKGROUND: Butenafine hydrochloride, a benzylamine derivative, exhibits potent fungicidal activity particularly against dermatophytes, aspergilli, dimorphic and dematiaceous fungi. OBJECTIVE: To review pharmacokinetics, mechanism of actions and clinical efficacy of butenafine against various dermatophytic and other superficial fungal infections. METHODS: Medline search was made using keyword butenafine. All English language articles were considered for this review. For inclusion in clinical efficacy section when ever available randomized controlled trials were considered a priority over other trials. RESULTS/CONCLUSIONS: The drug has excellent penetration into the epidermis and a prolonged retention time following topical application, conferring residual therapeutic activity after treatment cessation. Butenafine possess anti-inflammatory activity too. Topical butenafine 1% cream has been reported to be efficacious for tinea pedis, tinea corporis and tinea cruris in many randomized clinical trials when used for shorter duration. Its efficacy against pityriasis versicolor, seborrheic dermatitis and as anticandidal agent is not yet fully established.     

不同透皮促进剂对环吡酮胺和水杨酸体外经皮渗透性的影响

目的：以环吡酮胺和水杨酸为模型药物。研究透皮促进剂对外用抗真菌药的促透特性。方法：在离体透皮实验装置上进行透皮吸收试验和贮库效应的研究。结果：1%氮酮和1%薄荷醇联用对环吡酮胺经皮渗透的促进作用明显高于其它组，1%的薄荷醇对水杨酸促透效果最佳。而由1%氮酮。2.5%丙二酮，2.5%油酸，1%薄荷醇合用对环吡酮胺的体外经皮渗透虽具有明显的促进作用和时滞明显缩短。但是与二联使用透皮促进剂比较并无明显优点。结论：薄荷醇和氮酮对环吡酮胺和水杨酸体外经皮吸收具有显的促进作用。两联用对脂溶性化合物环吡酮胺的促透作用更明显。     

Use of an in vitro human skin permeation assay to assess bioequivalence of two topical cream formulations containing butenafine hydrochloride (1%, w/w)

The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream.     

Differences in penetration-enhancing effect of Azone through excised rabbit, rat, hairless mouse, guinea pig and human skins

The transdermal delivery of dihydroergotamine (DHE), from propylene glycol formulations with and without 6.0% laurocapram (Azone), and the penetration enhancing effect of Azone were evaluated in vitro on excised rabbit, rat, hairless mouse, guinea pig and human skins utilizing improved Franz diffusion cells. The steady-state flux of DHE from the propylene glycol formulation without Azone were 0.045, 0.270, 0.395, 0.128 and 10.035 μg/cm² per h across excised human, rat, guinea pig, rabbit and hairless mouse, respectively. Under the influence of the enhancer, Azone increased DHE penetration through excised skin of the various species used in this study in the following order: rabbit skin > human skin > rat skin > guinea pig skin > hairless mouse skin. The maximum enhancement factor of Azone (251.47) was obtained across rabbit skin and the minimum enhancing effect (14.44) was observed in the case of hairless mouse skin. The enhancement factor of Azone across human skin was 54.56. These results show that animal skins are poor models for human skin under the conditions used. The lag time of DHE, from the propylene glycol formulation containing 6.0% Azone, through human skin was longer than the lag times across all other skin species tested in this investigation.     

月桂氮酮对灭痤乳膏中盐酸克林霉素透皮吸收作用的影响

目的：研究不同浓度的月桂氮酮对盐酸克林霉素小鼠离体皮肤渗透性的影响。方法：用改良的Franze扩散池，选用不同浓度月桂氮酮(0，l％，2％和5％)作促渗剂，采用高效液相色谱法(HPLC法)测定盐酸克林霉素累积释放量(Q)、稳态流量(J)及渗透系数(Kp)。结果：与不含月桂氮酮的灭痤乳膏中盐酸克林霉素的Q值相比较，含1％月桂氮酮增加了67％，而含2％月桂氮酮则无显差异，当月桂氮酮浓度达5％时，Q反而降低了45％。结论：l％月桂氮酮对灭痤乳膏中盐酸克林霉素具有明显促渗作用。     

Animal models for percutaneous absorption

Animal models are important tools to predict human in vivo percutaneous absorption/penetration. Monkey, pig, rat, rabbit, guinea pig, hairless rodents, such as hairless rat, hairless mouse, hairless guinea pig and hairless dog, are among the most used animals for this purpose. Each animal model has its own advantages and weakness or limitation. To better correlate animal data with human skin absorption, we need to be familiar with each animal model's characteristics as well as experimental method and condition. We reviewed the original papers published after 1993 that described permeability of both animal skin and human skin. It showed that monkey, pig and hairless guinea pig are more predictive of human skin absorption/penetration and common laboratory animals, such as rat, rabbit, guinea pig, generally overestimate human skin absorption/penetration. Copyright © 2014 John Wiley & Sons, Ltd.