不锈钢微针经皮给药的研究

目的：将不锈钢微针阵列应用于经皮给药。考察离体大鼠皮肤经不同针形微针预处理相同时间、相同针形微针预处理不同时间后，模型药物鬼臼毒素经大鼠皮肤的透皮能力。方法：微针预处理大鼠皮肤后，用改进的Franz扩散池研究鬼臼毒素对皮肤的透皮速率。高效液相色谱法测定鬼臼毒素的含量。结果：皮肤经微针预处理后进行鬼臼毒素透皮，其透皮速率比未经微针处理时有明显提高。三角形微针、梯形微针、矛形微针对鬼臼毒素的促渗能力依次增强；三者所引起的鬼臼毒素在皮肤中的滞留量有显著差异。同种针形微针预处理皮肤时间越长，鬼臼毒素的透皮速率越大；但微针预处理时间对皮肤中的药物滞留量无显著影响。结论：微针用于药物经皮给药时，微针针形、微针的预处理时间对药物的经皮渗透具有重要影响。     

微针促渗仪经皮免疫部位对免疫应答的影响

目的 利用微针的促渗作用对小鼠进行经皮免疫,探讨不同免疫部位所引起免疫应答的特点.方法 用染色法和组织切片法考察微针促渗仪的穿刺能力和穿刺效果;采用微针促渗仪,对小鼠的后背皮肤和耳部皮肤进行处理,涂抹模型抗原卵清蛋白(OVA)和佐剂CpG ODN 1826后,采用ELISA法测定血清中的抗OVA特异性抗体.结果 微针促渗仪可成功穿刺皮肤角质层,将抗原OVA和佐剂CpG ODN 1826同时递送至皮肤表皮层.与经后背皮肤免疫比较,经耳部免疫会产生更强效的IgG、IgG 1和IgG 2a特异性抗体水平.结论 经皮免疫在耳部皮肤引起了比后背皮肤更强的免疫效果.     

经皮给药系统促渗方法研究的新进展

促渗方法的发展对于经皮给药的研究意义重大。笔者从化学促渗技术，包括化学促渗剂、前体药物、传递体、含醇脂质体、非离子表面活性剂脂质体和微乳；以及物理促渗技术，包括离子导入、电致孔、超声波促渗、微针、照相波、热致孔和磁场导入等诸多方面综述了近年来经皮给药促渗方法研究的新进展。     

多肽透皮给药研究进展

针对近年来多种多肽类药物的透皮给药系统进行综述。通过查阅国内外多种相关期刊文献。将多肽类药物透皮给药方法分为化学促渗剂、多种物理促渗技术,以及透皮肽、微针技术并对其进行论述。反向离子导入技术应用前景广阔,微针给药系统研究逐步深入,出现了胰岛素智能化微针给药系统,透皮肽的研究发展迅速,相信未来多种蛋白质及多肽的透皮给药方式将应用于临床,极大地促进医疗事业的发展。     

无痛微针透皮贴片对局部应用利多卡因的促渗作用

目的评价NS-TP-5B型无痛微针透皮贴片对局部应用利多卡因的透皮促渗效果及安全性.方法入选30名健康志愿者,采用随机、双盲、自身对照试验设计.每名志愿者左右臂随机分为试验组和对照组,分别采用无痛微针透皮贴片和模拟贴片处理,测定局部应用2%利多卡因注射液前后的疼痛评分.结果试验组20 min测定的疼痛评分与基线相比下降,且具有统计学意义(4.7±1.5 vs 6.1±1.5,P＜0.001).对照组20 min结果与基线相比无显著差异.结论无痛微针透皮贴片对局部应用利多卡因具有一定的透皮促渗作用.     

微针的特点及其在黄褐斑治疗中的应用研究分析

黄褐斑是一种后天获得性色素沉着性疾病，困扰患者的工作和生活。外用经皮给药的主要挑战是药物透过角质层屏障的阻碍。微针作为物理促渗方法和新的递药系统，能够穿透角质层形成特定的药物输送通道，促进了药物的渗透，提高了药物的生物利用度。本文主要总结了微针的特点，并以黄褐斑为切入点，分析微针近年来在黄褐斑领域的应用研究，为后续黄褐斑微针产品的开发提供一定的参考。     

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。     

促渗剂对氟比洛芬体外经皮渗透的影响

目的研究不同的促渗剂对氟比洛芬体外经皮渗透的促渗作用。方法采用TK-6A型透皮扩散仪,用人皮进行体外经皮渗透实验,考察不同的促渗剂[二甲基亚砜、月桂醇、丙二醇、月桂氮酮(氮酮)、尿素、油酸]及其组合对氟比洛芬体外透皮吸收的促渗作用,以HPLC法测定各时间点接受室中药物浓度,求算透皮吸收的有关参数,比较各促渗剂的促渗作用。结果15%二甲基亚砜、3%氮酮、1%尿素可使氟比洛芬经皮渗透速率分别提高1.8,1.5,1.1倍,促渗剂联用取得的促渗效果更佳,5%油酸 20%丙二醇 1%尿素可使该药物的经皮渗透速率提高6倍。结论单用促渗剂对氟比洛芬经皮渗透促渗效果有限,促渗剂联合使用可以显著提高氟比洛芬经皮渗透速率。     

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     

中药经皮给药促渗作用的研究概况

对促进中药经皮吸收的药剂学方法,即促进剂促渗和剂型因素对中药经皮给药促渗作用的研究概况进行综述。初步分析与探讨中药经皮给药研究中存在的问题与发展方向,为深入研究中药经皮给药制剂提供参考依据。     

盐酸丁螺环酮透皮促渗剂选择及其透皮机制的研究

目的研究透皮促渗剂对盐酸丁螺环酮体外经皮渗透的影响以及盐酸丁螺环酮的透皮机制。方法采用改良Franz扩散池,比较不同促渗剂种类、浓度、配比对盐酸丁螺环酮的促渗效果,同时通过改变扩散池的介质pH及皮肤的状态,研究药物的透皮机制。结果采用3%氮酮为透皮促渗剂时药物透过量最大。盐酸丁螺环酮随着分子型浓度的升高透过量也随之增加,皮肤去除角质层后,药物的透过量显著大于完整皮肤,而完整皮肤的贮库效应大于去角质皮肤。结论药物透皮以3%氮酮为透皮促进剂促渗效果最佳。盐酸丁螺环酮主要是以分子型透过皮肤,药物的透皮屏障与贮库效应发生的主要部位是皮肤的角质层。     

Effect of phosphatidylglycerol on the in vitro percutaneous drug penetration through the dorsal skin of guinea pigs,and analysis of the molecular mechanism,using (ATR-FTIR) spectroscopy

Standard in vito skin percutaneous penetration methods using excised guinea pig dorsal skin were employed, to characterize the penetration of a water-insoluble drug: tenoxicam (TEX), and a water-soluble drug: diclofenac sodium salt (DFS), enhanced by phosphatidylglycerol (PG); and an attenuated total reflectance fourier transform infrared (ATR-FTIR) spectroscopy was used to analyze the molecular mechanism of the drug penetration route. The C-H bond stretching absorbance frequency shift in the stratum corneum (SC) induced a higher and a broader absorbance, and the shift was dependent on the PG concentrations. The percutaneous penetration of TEX was dependent on the PG concentration (up to 6%). The enhancing mechanism of PG to TEX may not only increase the diffusion coefficient (D) and the partition coefficient (K) in the percutaneous TEX penetration but also increase fluidity of the route (intercellular lipid domain) for TEX, while that of PG to DFS, excepting 1%, PG system, may be increasing the D value in the percutaneous DFS penetration only. The percutaneous penetration of DFS was not dependent on the PG concentrations. Furthermore, the percutaneous penetration of TEX was proportional to the C-H bond stretching absorbance frequency shifts. In contrast, the percutaneous penetration of DFS was not proportional to the C-H bond stretching absorbance frequency shifts. Furthermore, the accumulation of TEX in skin was proportional to the C-H bond stretching absorbance frequency shifts. The striking parallel between the enhancement of the percutaneous penetration of TEX and the measured SC lipid fluidity shifts caused by PG, suggests that the transdermal water-insoluble drug penetration may be ultimately related to the SC lipid structure. Overall, these results suggest that PG mainly affects the intercellular lipid pathway (lipid-rich domains).     

Effect of polyunsaturated fatty acids and some conventional penetration enhancers on transdermal delivery of atenolol

The aim of our present study was to evaluate the in vitro percutaneous absorption of atenolol, a well-known antihypertensive, from a series of formulations containing various penetration enhancers. Particularly the promoting effect of EPA and DHA, two polyunsaturated fatty acids (PUFAs), has been studied, and drug permeation data have been compared with those obtained with the other formulations containing "classic" penetration enhancers such as transcutol, d-limonene, and PG. Not all the penetration enhancers tested were effective in increasing atenolol percutaneous flux and the best permeation profile for atenolol was obtained with the formulation containing transcutol (B) and PUFA (E). To explain the enhancer mechanism, the atenolol diffusion and partitioning coefficients from the different formulations were calculated. The results indicated that PUFAs increased the apparent diffusion coefficient of the drugs but did not affect their apparent stratum corneum (SC)/vehicle partition coefficient (K(m)). At this same time transcutol exerted its enhancer effect increasing significantly the apparent SC/vehicle partition coefficient (K(m)) and in a minor amount the apparent diffusion coefficient of skin permeation process (D(m)). The potential application of formulations B and E in atenolol percutaneous absorption was determined from the calculation of the steady-state plasma concentrations (C(ss)). These values resulted within the drug therapeutic range and suggest that atenolol transdermal delivery could be feasible.     

Evaluation of percutaneous absorption of midazolam by terpenes

Midazolam is a highly lipophilic drug that is widely used in preanesthetic medication. Recently, terpenes have been reported to show an enhancing effect on percutaneous absorption of drugs. The effect of terpenes (l-menthol, d-limonene, RS-(+/-)-beta-citronellol, geraniol) on the in vitro percutaneous absorption of midazolam through rat skin was evaluated using unjacketed Franz diffusion cells. Since midazolam is a lipophilic drug, percutaneous penetration is low and a percutaneous penetration enhancer is necessary for its percutaneous absorption. The terpenes (5%, w/v) in combination with 30% ethanol, and 20% propylene glycol significantly increased the percutaneous absorption of midazolam in comparison to the control. In vitro data suggested that d-limonene is the most effective enhancer among terpenes and other penetration enhancers such as Azone. In in vivo percutaneous absorption assays, the midazolam formulation using d-limonene could penetrate through rat skin, but the other terpenes could not penetrate. In conclusion, d-limonene in combination with ethanol can be used to enhance the percutaneous absorption of the highly lipophilic drug midazolam.     

醇传递体在透皮给药系统中的研究进展

由于角质层的限速屏障作用,大部分药物透过皮肤的能力较差。醇传递体因能够将药物传递到皮肤深层和全身循环,且制备方法简单,使用安全而受到关注,为药物的经皮渗透提供了新的传递载体。醇传递体具有高度变形性、促进药物经皮渗透、缓释、防止药物代谢降解等优点,在药物的经皮吸收方面具有广阔的应用价值和开发前景。本文通过查阅国内外文献对醇传递体在透皮给药系统中的研究和应用等方面进行综述,为其今后在透皮领域的进一步发展提供借鉴。     

Percutaneous penetration enhancers: an overview

Transdermal drug delivery is the controlled release of drugs through the skin to obtain therapeutic levels systematically. Several technological advances have been made in the recent decades to enhance percutaneous drug penetration. This overview focuses on the physical, biochemical, and chemical means of penetration enhancement, as well as the classification and mechanisms of chemical penetration enhancers, their application in transdermal drug delivery, and trends and development in penetration enhancement.     

The influence of azone® on the percutaneous absorption of methotrexate

The percutaneous absorption of the polar drug methotrexate has been examined in vitro. Two alcoholic gel formulations containing 1% methotrexate with or without Azone® were applied to full-thickness abdominal human skin mounted in all-glass Franz-type diffusion cells. In the absence of Azone® no percutaneous penetration of methotrexate was observed. In the presence of Azone® 190 ng/cm² permeated after 48 h. Azone® appears to be actingas an efficient penetration enhancer for this drug.     

Assessment of the percutaneous penetration of indomethacin from soybean oil microemulsion: effects of the HLB value of mixed surfactants

The objective of this study was to evaluate the influence of the ratios or the hydrophile-lipophile balance (HLB) values of Cremophor EL and Span 80 on the phase behavior of the O/W microemulsions and the percutaneous absorption and penetration of indomethacin microemulsions. The existence of microemulsion regions is investigated in quaternary systems composed of soybean oil/Cremophor EL and Span 80 (mixed surfactants)/diethylene glycol monoethyl ether (cosurfactant)/water by constructing pseudo-ternary phase diagrams at various Cremophor EL/Span 80 ratios. In addition, five microemulsion formulations with various mixed surfactants HLB values were evaluated by in vitro penetration experiments using mouse skin and Franz diffusion cells. The flux and amount of indomethacin penetration from 5 microemulsion formulations were significantly different from the control, and the enhance ratios ranged from 2.38 to 4.68 and 2.11 to 4.23, respectively. The HLB value of mixed surfactants in the formulations was a principal factor in determining the percutaneous penetration of the drug. The flux and amount of drug penetration increased gradually with increasing content of the lipophilic surfactant Span 80 and skin retention was highest for mixed surfactants with a HLB value of 7.6. Therefore, it is suggested that the presence of mixed surfactants was beneficial in the formation of O/W microemulsions and enhanced percutaneous penetration of indomethacin.     

派瑞松乳膏中3种药物透皮特性的研究

目的:评价派瑞松乳膏中曲安奈德(TACA)、苯甲酸(BEN)、硝酸益康唑(ECN)3种药物的透皮特性.方法:采用Franz扩散池法,考察药物经完整皮肤和去角质层皮肤的体外透皮能力,并采用了胶带剥离、皮肤萃取法分别获取了皮肤角质层、去角质层皮肤样本,用HPLC法测定了样本中的药物含量.结果:经过24 h透皮吸收,TACA和BEN的去角质层皮肤渗透量分别为完整皮肤的1.5和1.3倍,ECN的渗透量基本为零.8h透皮实验,TACA高、中、低3个浓度角质层中药物含量基本相同,真皮层则存在浓度依赖现象;ECN在皮肤各层和接受室均检测不到;BEN在角质层和真皮层中的分布与TACA相似,但透过量比TACA大.结论:角质层是皮肤渗透的重要屏障,派瑞松乳膏应用于皮肤溃疡、受损或者婴幼儿皮肤仍需谨慎.     

咳喘穴位贴片体外透皮速率和体外释放规律研究

目的:研究咳喘穴位贴片体外透皮速率和体外释放规律。方法:采用高效液相色谱法测定透皮接受液和释放液中指标成分盐酸麻黄碱的浓度,计算其渗透速率和体外释药速率。结果:麻黄碱以6.4679μg.cm-2.h-1/2的速率恒速渗透,其体外释药速率为21.382μg.cm-2.h-1/2,其释放过程符合Higuchi方程。结论:咳喘穴位贴片可研制为皮肤限速型的骨架控释系统。