双戊烯对酮康唑透皮吸收促进作用

目的：研究双戊烯的透皮促进作用。方法：采用自制透皮扩散装置。以离体小白鼠背部皮肤为透皮屏障，紫外分光光度法测定含不同浓度双戊烯和氮酮对酮康唑的促透效果。结果：不同浓度促进剂对酮康唑的促透效果顺序为3％双戊烯＞2％双戊烯＞3％氮酮＞1％双戊烯。结论：实验证明，3％双戊烯对酮康唑具有较好的促透作用，与其它浓度的双戊烯和不同浓度的氮酮相比具有显著性差异（P＜0．05）或极显著性差异（P＜0．01）。     

乙肝疫苗体外经大鼠皮肤渗透与离子导入给药特性研究(英文)

对乙肝疫苗进行体外经皮实验以评价疫苗在被动扩散和离子导入情况下的经皮渗透特性。体外透皮研究采用Franz扩散池,以SD大鼠的腹部皮肤为渗透屏障,以酶联免疫法测定药物累积渗透量和在皮肤中的滞留量。乙肝疫苗(质量浓度为23μg·mL-1与46μg·mL-1)经完整皮肤被动扩散的经皮渗透量与皮肤滞留量均极少,24 h累积渗透量仅(2.1±0.1)ng.cm-2和(2.3±0.1)ng.cm-2。去除角质层后,经皮渗透量与皮肤滞留量分别提高至(383.7±86.2)ng.cm-2和(16.8±4.6)ng.cm-2,是完整皮肤的171.6倍与2.1倍(46μg·mL-1)。离子导入对于乙肝疫苗具有明显的经皮渗透促进作用:完整皮肤经皮离子导入6 h,乙肝疫苗的累积渗透量是被动扩散6 h的2.7倍(23μg·mL-1)和6.6倍(46μg·mL-1);去角质层皮肤离子导入,乙肝疫苗的累积渗透量是被动扩散6 h的1.6倍(23μg·mL-1)和1.8倍(46μg·mL-1)。离子导入也能显著增加疫苗在皮肤中的滞留量。离子导入6 h疫苗在完整皮肤中的滞留量和去角质层皮肤中的滞留量均与被动扩散24 h的皮肤滞留量接近[完整皮肤...     

Nortriptyline hydrochloride skin absorption: Development of a transdermal patch

The influence of propylen glycol (PG), ethanol, and oleic acid (OA) on nortriptyline hydrochloride (NTH) penetration through human epidermis was studied in vitro at two different pH values (5.5 and 7.4). The influence of lactic acid and polysorbate 80 was studied for a pH of 5.5. Permeation studies through Heat Separated Epidermis, as well as the enhancing effect of the different vehicles, showed a pH dependency. A pH value of 5.5 in the donor solution decreases significantly the permeability coefficient (Kp) with respect to a pH value of 7.4 (0.011+/-0.004 x 10(-6) versus 0.36+/-0.04 x 10(-6)cm/s). The vehicles showed an increasing enhancement effect in the order: polysorbate 80>ethanol/PG/OA>PG>ethanol>ethanol/lactic acid>lactic acid at pH 5.5 while they reduced the permeation of NTH at pH 7.4. Considering the results obtained at pH 5.5, the maximum enhancement ratios were found for polysorbate 80 and the combination ethanol/PG/OA (10.72 and 3.90). Both vehicles were selected for designing a NTH transdermal delivery system (NTH-TDS) using (hydroxypropyl)methyl-cellulose as polymer. The NTH-TDS based on the combination of ethanol/PG/OA showed an enhancement ratio with respect to control of 2.09 and the addition of polysorbate 80 to the matrix, of 5.82.     

In vitro and in vivo evaluation of a hydrogel-based prototype transdermal patch system of alfuzosin hydrochloride

The first-line therapy for moderate to severe benign prostatic hyperplasia is the oral therapy by alfuzosin hydrochloride. Unfortunately, the oral therapy of alfuzosin is associated with several route-specific systemic side-effects. The current study was aimed to develop a prototype transdermal patch system for alfuzosin using a hydrogel polymer and optimize the drug delivery through the skin for systemic therapy. The prospective of different chemical enhancers (polyethylene glycol (PEG 400), isopropyl myristate, propylene glycol, menthol and L-methionine; 5% w/v) and iontophoresis (0.3?mA/cm²) in the alfuzosin delivery across the full thickness rat skin was assessed in vitro. In vivo iontophoretic studies were carried out using selected patch system (PEG 400) for a period of 6?h in Sprague-Dawley rats. Passive permeation studies indicated that the incorporation of chemical agents have moderate effect (~?4- to 7-fold) on the alfuzosin skin permeability and reduced the lag time. Combined approach of iontophoresis with chemical enhancers significantly augmented the drug transport (~ 43- to 72-fold). In vivo pharmacokinetic parameters revealed that the iontophoresis (transdermal patch with PEG 400) significantly enhanced the C_max (~ 3-fold) and AUC_0-α (~ 4-fold), when compared to control. The current study concludes that the application of iontophoresis (0.3?mA/cm²) using the newly developed agaorse-based prototype patch with PEG 400 could be utilized for the successful delivery of alfuzosin by transdermal route.     

麻黄素滴鼻液的透皮吸收研究

目的 研究麻黄素滴鼻液的体外透皮吸收情况，为该药的继续开发提供实验依据。方法 采用体外扩散池，以小鼠皮肤作为屏障，通过高效液相紫外检测器检测不同时间透过小鼠皮肤的盐酸麻黄碱的含量，观察其透皮吸收情况。结果 盐酸麻黄碱24h的累积透皮吸收百分率为28％。结论 麻黄素滴鼻液的透皮吸收较好，适合局部用药，具有较好的前景。     

双戊烯对替硝唑透皮吸收促进作用的研究

目的：研究双戊烯对替硝唑的促透效果,为透皮促进剂的选择提供参考。方法：通过离体小鼠皮肤渗稼透释药实验,测定含不同浓度双戊烯和氮酮对替硝唑溶液促透效果。结果：不同浓度促透剂对替硝唑的透皮吸收促进效果大小顺序为3％双戊烯＞2％双戊烯≈4％氮酮＞3％氮酮。结论：3％双戊烯对替硝唑溶液有显著的透皮促进作用,与其他浓度的双戊烯和氮酮相比具有显著差异（P＜0.05)。     

月桂氮酮促进敏乐啶透皮吸收作用的初探

目的:研究月桂氮酮对敏乐啶的透皮吸收的影响.方法:采用水平双室装置,通过用紫外分光光度法测定接受池中敏乐键的含量而计算敏乐啶的透过量.结果:敏乐啶的渗透系数为77.85×10~(-4)cm/h,月桂氮酮促进敏乐啶的透皮吸收6.4倍.结论:月桂氮酮能促进敏乐啶的透皮吸收,与临床结果相符合.     

Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin

The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm² resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel and when combined with iontophoresis it was possible to deliver 10 mg/cm²/day of buspirone hydrochloride.     

氮酮对葛根素透皮吸收作用的实验研究

本实验采用简单小室法，以离体仔猪皮为透皮屏障，以生理盐不为接受液，研究了不同浓度的氮酮对葛根素透皮吸收作用的影响，实验结果表明，经皮吸上１２ｈ，含氮酮１％、２％、３％各个组之间，以及与不同氮酮的对照组之间，其透皮吸收率在统计学上极显著差异（Ｐ＜０．０１）。     

Effect of terpenes on transdermal iontophoretic delivery of diclofenac potassium under constant voltage

Objective: The aim of the study was to enhance the transdermal delivery of diclofenac potassium (DP) from hydrogels by constant voltage iontophoresis (CVI). The other objective was to establish the safety and efficacy of CVI in rats.

Materials and methods: Hydrogels of DP were developed using hydroxyethyl cellulose as matrix material and geraniol, l-menthol and thymol as iontophoretic efficiency enhancers (IEE). In vitro permeation of hydrogels under CVI (1.5?V) was performed in Franz diffusion cells across porcine skin. The ability of CVI to deliver therapeutic amount of DP in vivo was assessed in rat paw edema model.

Results: CVI significantly (p?l-menthol enhanced the iontophoretic flux of DP by ～4.75 and ～4.49 fold, respectively compared to passive control. The in vivo studies indicated that CVI in combination with IEE, significantly reduced (p?r?=?0.996) was noted between in vitro flux values and AUC of % inflammation.

Conclusion: The preclinical studies conclusively demonstrated that CVI in combination with IEE’s such as geraniol or l-menthol has the potential to safely deliver therapeutic amounts of DP.     

氮酮对消炎止痒搽剂中黄芩苷透皮吸收的影响研究

目的研究消炎止痒搽剂中不同氮酮浓度对黄芩苷的离体透皮吸收特性,为该制剂的制备工艺提供依据。方法以离体sD大鼠腹部皮肤为渗透屏障,采用Franz垂直扩散池,以UPLC测定接受液中黄芩苷的含量,考察不同氮酮浓度对黄芩苷累积透皮吸收量的影响。结果与不含氮酮促进剂相比,氮酮可以促进黄芩苷的吸收,且浓度对黄芩苷的透皮吸收有影响,其中氮酮浓度2．5％时,黄芩苷的累积透皮吸收量最大,渗透率为0．4932Ixg·cm-2·h-1。结论氮酮可以促进}肖炎止痒搽剂中黄芩苷的透皮吸收,浓度为2．5％时效果较好。     

促进剂对酮洛芬巴布剂体外透皮性的影响探讨

目的:通过几种常用促进剂对酮洛芬巴布剂体外促渗作用研究,筛选出适合用于酮洛芬巴布剂的透皮促进剂。方法:分别制备单独含2%或4%的桉叶油、油酸、薄荷脑、聚乙二醇400、月桂氮芯卓酮、聚山梨醇酯-80的酮洛芬巴布剂贴片,以及4%的桉叶油分别与2%的油酸、薄荷脑、聚乙二醇400合用的酮洛芬巴布剂贴片,采用改良Franz透皮扩散池,以离体小鼠背部皮肤为透皮屏障,贴敷12h,以渗透速率及12h累积渗透量为指标,探讨促进剂对酮洛芬体外透皮性的影响。结果:与空白组对照,2%聚山梨醇酯-80、2%月桂氮卓芯酮单独使用不能明显提高酮洛芬的渗透速率(P>0.05),4%聚山梨醇酯-80、4%月桂氮卓芯酮和其他的促进剂都能明显的提高酮洛芬的经皮渗透(P<0.01),对酮洛芬透皮速率提高大小顺序为油酸≥桉叶油>薄荷脑>聚乙二醇400>月桂氮卓芯酮>聚山梨醇酯-80。结论:油酸、桉叶油、薄荷脑、聚乙二醇400均可作为酮洛芬巴布剂透皮促进剂。     

睾酮凝胶体外透皮吸收的特征

目的建立睾酮凝胶剂体外透皮吸收试验方法并考察其体外经皮吸收特性。方法采用单室扩散池,大鼠皮肤作为试验材料,以乙醇-生理盐水（3：7,V/V）为接收液,恒温32℃,分别于设定时间取样,用HPLC法测定接受液中睾酮含量。结果累积渗透量Q（μg·cm^-2）对t（h）进行线性回归,方程为Q=108．7069t＋65．4318,r=0．9968,求算透皮速率常数J为108．7μg·cm^-2·h^-1。结论所建立的体外透皮吸收模型和方法可以较好评价睾酮凝胶剂的体外透皮吸收特性。     

The effect of pretreatment with terpenes on transdermal iontophoretic delivery of arginine vasopressin

This study investigates the effects of terpenes and iontophoresis on the in vitro permeation of arginine vasopressin (AVP) through rat skin and the biophysical changes induced by the chemical enhancers in the stratum corneum (SC) lipids by FT-IR spectroscopy. Pretreatment with terpenes (e.g. 5% w/v, carvone, pulegone, cineole and menthol in EtOH:W (2:1) system) increased (P < 0.05) the flux of AVP in comparison to control (not pretreated with enhancer) but was not significantly different (P > 0.05) in comparison to iontophoresis. Amongst different terpenes studied maximum enhancement ratio was observed with cineole. In combination, iontophoresis did not further increase (P > 0.05) the permeation of AVP through the enhancer pretreated epidermis in comparison to pretreatment with enhancer or iontophoresis alone. Hence it was concluded that although the combination was effective in flux enhancement compared to control, there was no synergism in action between terpenes and iontophoresis. FT-IR spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The area under the symmetric and asymmetric stretching peaks at 2850 and 2920 cm(-1) revealed that at the concentration used terpenes did not extract any lipids from the epidermis. The mode of action of terpenes is attributed to the breaking of hydrogen bonds between the ceramide head groups of lipids in the SC leading to greater fluidization of the SC lipids.     

Current Status and Future Prospects of Transdermal Drug Delivery

Pharmaceutical Research -     

羟乙桂胺离子导入和涂抹兔体透皮吸收的对比

采用离子导入和直接经皮给药方法，以高效液相色谱法研究了羟乙桂胺乳剂（1．5g／40cm2）对10只家兔的透皮吸收及药物动力学。结果表明，离子导入方法组平均值（n=5）Ka为1．57h-1，T1／2α为1．15h和AUC为16．05μg·h·ml-1。离子导人组与直接外敷组Cmax、Tmax和AUC均有显著性差异（P＜0．01），表明离子导入方法组较涂抹给药的透皮吸收性能好。     

盐酸小檗碱透皮吸收软膏剂处方的筛选

目的筛选盐酸小檗碱透皮吸收软膏剂处方。方法采用半透膜扩散法对不同处方的药物释放度进行测定,依据溶出曲线对处方进行筛选。结果与结论以甘油、羧甲基纤维素钠、透明质酸为基质的盐酸小檗碱透皮吸收软膏剂,主药的释放达到缓释效果,溶出度符合药典标准,且重复性好,是最佳处方。     

Determination of Lidocaine Concentrations in Skin After Transdermal Iontophoresis: Effects of Vasoactive Drugs

The purpose of this study was to investigate the effect of vasoactive drugs on transdermal lidocaine iontophoresis by measuring the concentrations of radiolabeled lidocaine which has penetrated the skin. Previous studies had demonstrated that coiontophoresis of vasoactive drugs could modulate the transcutaneous flux of lidocaine and suggested that a dermal depot of lidocaine was involved. To address this, lidocaine hydrochloride (¹⁴C) was iontophoresed in vivo in anesthetized weanling pigs either alone or with the vasodilator tolazoline or the vasoconstrictor norepinephrine. Tissue cores under the active electrode were then collected, quick-frozen, and sectioned on a cryostat, and then the radioactivity was determined in each 40-µm section. Coiontophoresis with norepinephrine resulted in increased concentrations of lidocaine in skin up to a depth of 3 mm. These concentrations decreased to lidocaine-alone levels after a 4-hr washout. Tolazoline decreased tissue concentrations of lidocaine. Concentrations were intermediate when lidocaine alone was administered. These studies support the hypothesis that coiontophoresis of vasoactive drugs modulates the transdermal delivery of lidocaine, in part by altering the cutaneous depot.     

氮酮对班布特罗透皮吸收的促渗作用研究

目的 研究班布特罗的经皮渗透性，并考察不同浓度的氮酮对其的影响。方法以30％乙醇-水溶液为接受液，采用Valia-Chien水平扩散池进行大鼠离体皮肤的渗透实验。结果不同浓度的氮酮对班布特罗的促渗作用不同。结论 由t检验及SPSS曲线拟和的结果可知，氮酮对班布特罗透皮吸收的促进作用具有浓度依赖性，氮酮的最佳促渗浓度为5％，增渗比ER为8．58。