透皮促渗方法研究的新进展

相对于传统的给药方式,透皮给药有着无可比拟的优势。许多促渗方法已经被应用于增强皮肤的通透性和药物传导速率。本文报道了促渗方法的最新研究进展和应用,包括化学促渗剂、脂质体、微乳、前体药、肽类、离子导入、电致孔以及各种方法的联用技术等。     

药物经皮吸收的物理促渗方法

经皮给药系统为一些长期疾病和慢性疾病的治疗和预防创造了一种简单、方便和行之有效的给药方式。在经皮给药制剂的研究中，如何促进药物的经皮吸收以达到治疗浓度是研究的关键。目前采用的经皮促渗方法除了采用化学促渗剂、脂质体外．还有一些物理促渗方法——离子导入法、电致孔技术和超声波导入。     

物理技术促进药物经皮吸收的研究进展

目的:为加强经皮给药制剂的开发与应用提供参考。方法:以"微针""驻极体""离子导入""经皮给药系统""促渗""Microneedle""Electret""Inotophoresis""Transdermal drug delivery system"等为关键词,组合查询2001年1月-2017年2月在PubMed、ScienceDirect、中国知网、万方、维普等数据库中的相关文献,对促进药物经皮吸收的物理技术的研究进行综述。结果与结论:共检索到相关文献584篇,其中有效文献65篇。常用的单一物理技术促渗方法有微针、驻极体、离子、超声、电致孔、激光、磁场导入、热穿孔。其中,微针经皮给药适用于大分子药物(如皮肤渗透率较低的多肽、蛋白质和疫苗等);微针的针体长度、形状以及硬度、针壁厚度、载药量、滞留时间和体内降解问题是今后重点的研究对象。驻极体对离子型药物和非离子型药物都有良好的透皮促渗作用,但对离子型药物效果更佳;国内对于驻极体促渗的实验研究少,目前其临床应用无相关报道。离子导入、电致孔促渗在中药中的运用较热门,适用于电离性能较好的小分子药物(如胰岛素),但依赖带电装置及能量的特点导致推广受限。离子导入适用于慢性疾病如癌症和糖尿病的治疗;今后研究重点在于明确导入体内发挥作用的主要成分及其作用机制。超声导入主要适用于水溶性好的药物(如多肽和蛋白质);加强系统的安全性研究以及空化作用的机制研究、改善装置设计缺陷是今后研究的重点。利用激光破坏表皮的屏障作用促进药物经皮吸收,在医药领域应用前景良好。目前磁场导入与热穿孔技术促渗的国内外相关文献报道较少,今后的重点是加强这两者的机制、优化装置性能研究以及解决安全性问题。两种或多种物理技术的联用尽管能大大提高药物经皮透过率,但制作的复杂性和高成本是亟需突破的难题。     

药物因素对电致孔-离子导人体外经皮联合促渗技术的影响

以氧化苦参碱、苦参碱、盐酸小檗碱、氨茶碱和秋水仙碱五种生物碱以及水杨酸、水杨酸钠和水杨酰胺为模型药物,采用电致孔一离子导入并用技术进行体外经皮给药途径的试验。结果得出药物分子量的大小、油／水分配系数、药物熔点、浓度、解离性质四种药物因素和不同部位皮肤的生理因素是影响电致孔一离子导入联合促渗技术的主要因素。     

物理方法促进胰岛素经皮吸收的实验研究进展

目的胰岛素经皮吸收制剂是一种理想的胰岛素给药方式,但由于皮肤角质层的阻力、胰岛素分子在皮肤中的累积等因素限制了胰岛素的经皮给药。方法本文介绍了微针、电致孔、超声导入、离子导入等物理方法促进胰岛素经皮吸收实验研究进展。结果研究安全、有效、经济、方便的胰岛素透皮吸收物理促渗技术。结论随着对上述新技术、新方法实验研究的深入,物理促渗技术必将为胰岛素透皮吸收制剂的发展开辟更广阔的前景     

促进多肽和蛋白质类药物透皮给药技术的研究进展

综述了近年来以物理方法促进多肽和蛋白质药物透皮给药技术研究的进展，包括目前广泛研究的离子导入、电致孔导入和超声导入技术。     

离子导入经皮给药系统

综述了离子导入技术的基本组成、促渗机制、影响因素及应用前景。离子导入技术可有效提高药物的经皮渗透性，该技术扩大了经皮给药系统的研究范围，其对多肽和蛋白质等大分子药物的透皮促渗作用日益受到关注。     

柔性脂质体的促渗作用研究

本文以水杨酸钠为模型药，系统研究了不同柔性脂质体的经皮促渗能力，实验结果表明掺有强亲水性表面活性剂的脂质体具有很好的促渗作用，是一类新的透皮促进剂。     

化学促渗剂预处理与电致孔联用促进大鼠皮肤滞留环孢素A

目的：考察化学促渗剂预处理与电致孔联用对大鼠皮肤滞留环孢素A的促进作用。方法：使用化学促渗剂预处理大鼠皮肤2h后，将含有0．5％环孢素A的40％乙醇混悬液应用于离体大鼠皮肤，同时在大鼠皮肤上施加电致孔。结果：氮酮和薄荷醇预处理皮肤和电致孔联用可明显提高环孢素A在大鼠表皮和真皮的滞留，与对照组相比，滞留量分别是对照组的10．4和11．7倍。结论：氮酮和薄荷醇预处理皮肤和电致孔联用具有协同作用，能够显著提高环孢素A在大鼠表皮和真皮中的滞留。     

透皮促渗方法联合应用的研究进展

透皮给药系统具有传统给药方式不可比拟的优势。但由于药物的低渗透量，使其应用受到一定限制。各种物理的、化学的促渗方法，包括透皮吸收促进剂、超声导入法、离子导入法、电穿孔法等可改善皮肤透过性，增加药物的透皮速率。而且几种方法联合应用的促渗效果更加显著。本文总结了近年来各种促渗方法联合应用的研究进展。     

性激素类药物经皮给药制剂研究进展

介绍了近年来国内外性激素类药物经皮给药制剂的研究进展,包括化学促渗技术以及新剂型技术在此方面的应用情况,旨在为性激素类药物经皮给药制剂的深度开发提供参考。经皮给药制剂可避免肝脏首过效应,显著延长药物作用时间,为需长期用药尤其是性激素类药物的使用者提供了一个新的治疗选择。     

蛇床子挥发油和氮酮促透作用的比较

目的对蛇床子挥发油和氮酮促透作用进行比较,为蛇床子挥发油的应用提供理论依据.方法在离体透皮实验装置上进行透皮吸收实验和贮库效应的研究.结果蛇床子挥发油和氮酮单独应用时对甲硝唑经皮渗透均有显著的促进作用,增渗倍数分别为2.48和2.21;两者合用时促透作用显著增强.单独应用时,对甲硝唑经皮渗透的贮库效应影响不明显,但合用时效果显著增加.结论蛇床子挥发油和氮酮对甲硝唑的促透作用强度相当,合用时效果明显增强.     

新型载体材料巯基壳聚糖的研究进展

巯基壳聚糖是一类新型功能性聚合物,与未修饰的壳聚糖相比,黏附性和促渗作用均显著增加。现对其化学合成、理化性质、生物学特性、安全性评价以及在给药系统中的应用进行综述,旨在为药物递送系统提供新的研究思路和方法。     

醋酸烯诺孕酮透皮贴剂的制备及不同促渗剂对其促渗作用考察

目的：制备醋酸烯诺孕酮透皮贴剂,并考察5种促渗剂单用和联用对贴剂的促渗作用。方法：采用正交试验,以初黏力和累积渗透量（Q）为指标,优化Druo-tak87-2287压敏胶、聚维酮（PVP）K30、乙酰丙酮铝的用量,考察250h内的平均Q;比较质量分数均为5%的氮酮（Azone）、油酸（OA）、肉豆蔻酸异丙酯（IPM）、桉叶油（OE）和丙二醇（PG）及1%、3%、5%、7%OE和3%OE＋1%Azone、3%OE＋3%Azone、3%OE＋5%Azone的贴剂250h内的Q、透皮速率常数（Jss）及增渗倍数。结果：压敏胶、PVPK30、乙酰丙酮铝的用量分别为15、2、0.03g,250h的平均Q为60.83μg/cm2;5%OE单用时250h内的Q最大,为118.12μg/cm2,Jss为0.71μg/（cm2·h）,增渗倍数为2.2;3%OE＋5%Azone联用时250h内的Q最大,为175.96μg/cm2,Jss为1.102μg（/cm2·h）,增渗倍数为3.22。结论：所制备的贴剂初黏力符合要求,3%OE＋5%Azone对醋酸烯诺孕酮透皮贴剂有明显促渗作用。     

Advanced techniques for penetration enhancement in transdermal drug delivery system

Transdermal route has been recognized as a promising drug delivery system for systemic delivery of drugs and provides the advantage of avoidance of first-pass effect, ease of use, better patient compliance, maintaining constant blood level for longer period of time and decrease side effects. The major pitfalls of this route lie with difficulty in permeation of drugs through the skin. Several literatures have been published for enhancing the permeation of drugs by chemical approaches. However the present review highlighted about the advanced physical techniques used for enhancing delivery of drugs such as structure-based, electrically based, velocity based and several other miscellaneous physical techniques for enhancing the permeation of drugs. In addition to these, the present review also gives an exhaustive account on clinical data about these techniques and regulatory considerations for new drugs as well as generic product approval in transdermal drug delivery.     

Iontophoretic drug delivery across human nail

Topical trans-nail delivery of antifungal drugs is limited by several physicochemical and physiological factors. Use of chemical permeation enhancers has been a common approach for enhancing trans-nail delivery of drugs. The potential of physical permeation enhancement techniques has been found to be higher than the potential of chemical permeation enhancers in transdermal delivery of hydrophilic drugs and macromolecular therapeutic agents. However, application of physical permeation enhancement techniques has not been explored for trans-nail drug delivery. In the current work, iontophoresis was applied across human nail in vitro to assess its efficiency in enhancing drug delivery. Salicylic acid (SA) was used as test diffusant. The influence of pH, ionic strength, and current density was studied. Obviously, increase in current density increased the trans-nail transport flux. It appears that about 50-100 mM ionic strength is required for optimal conduction of electric current across nail. The flux enhancement factor (iontophoretic flux/passive flux) also increased with increase in pH due to increased ionization of SA. This study demonstrates the efficacy of iontophoresis in enhancing the trans-nail delivery of drugs.     

Estimation of Transdermal Permeation Parameters in Non-stationary Diffusion Experiments. Application to Pre-treatment Studies with Terpenes

No HeadingPurpose. To estimate the applicability of transdermal drug permeation parameters in a finite-dose model for skin pre-treated with terpenes and to evaluate the enhancing effect of some terpene formulations on alprazolam permeation.Methods. In vitro enhancement of alprazolam human skin permeation was investigated using a pre-treatment with different terpene solutions. Vertical diffusion, Franz-type cells were used. Intrinsic drug permeation was also investigated. Transdermal permeation parameters were estimated from the per-meation tabulates using different theoretical approaches for their calculation. Two groups of permeation parameters were calculated: modelistic (diffusion of a finite-dose of drug model) and parameters non-dependent of a diffusional model.Results. In control experiments, all approaches of data treatment satisfactorily described the experimental permeation profiles. When skin pre-treatment was investigated, the fitting of a mathematical sigmoid function was much better than the diffusional approach. Pre-treatment of the skin with Limonene dissolved in ethanol / propylene glycol and Menthol dissolved in propylene glycol increased 15 and 10 times respectively the permeation parameters of alprazolam.Conclusions. Using enhancers that are rapidly cleared from the skin, skin permeability does not remain constant during the permeation experiment and therefore it is not possible to calculate parameters that are usually true coefficients or definite values. In this case, non-modelistic parameters can be used to estimate an enhancing effect.     

Evaluation of skin permeation and accumulation profiles of a highly lipophilic fatty ester

The aim was to evaluate the skin permeation and accumulation profiles of a highly lipophilic fatty ester using the combination of various permeation enhancing techniques to study the potential of highly lipophilic fatty esters as local topical agents. Permeation and accumulation profiles of ketorolac stearate (C18:0) were studied using solubility improved formulation, supersaturated solution of permeant in enhancer vehicle, lipophilic receptor solution, enhancer pretreatment, and the removal of stratum corneum and delipidization of skins. Impermeability and minimal skin accumulation of ketorolac stearate could delineate a preliminary possibility for designing safer topical agents without systemic absorption.     

萜烯类手性促进剂对氟比洛芬经皮渗透对映体选择性的影响

目的:考察萜烯类手性促进剂芳樟醇和薄荷醇对氟比洛芬(flurbiprofen,FP)经皮渗透的对映体选择性作用.方法:采用Valia-Chien双室渗透扩散池,以大鼠离体皮肤为渗透屏障,以稳态经皮渗透速率为评价指标,用对映体选择性高效液相色谱法对FP对映体进行浓度测定,考察手性促进剂芳樟醇或薄荷醇对FP对映体选择性的影响.结果:无论供给液是否含单个对映体或消旋体,若供给液中不含促透剂,FP经大鼠离体皮肤渗透未见对映体选择性.当供给液中含有dl-薄荷醇时,RS-FP的稳态渗透速率分别为R-FP、S-FP的1.34,1.27倍,差异有显著性(P <0.05);而供给液中含有l-薄荷醇时,FP对映体及消旋体间的皮肤渗透速率无显著差异(P >0.05).l-薄荷醇和dl-薄荷醇对同一药物构型R-FP或S-FP 的促透效果相当;然而,dl-薄荷醇对RS-FP的促透作用是l-薄荷醇的1.44倍.l-芳樟醇或dl-芳樟醇作为手性促透剂时,未发现对映体选择性渗透现象.结论:dl-薄荷醇对FP的促透作用出现了对映体选择性,而l-薄荷醇、l-芳樟醇和dl-芳樟醇未引起FP的对映体选择性渗透,且所有渗透实验均未发现对映体转化.