曲安奈德经皮渗透特性研究

目的评价曲安奈德经皮渗透的特性。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,考察曲安奈德在皮肤不同层的分布情况。结果曲安奈德的24 h透过量去角质层皮肤约为完整皮肤的1.6倍;8 h透皮实验,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。结论角质层是曲安奈德的透皮吸收重要屏障,但角质层对药物的储留有饱和现象,临床上应用时需特别关注。     

曲安奈德经皮渗透特性研究

目的 评价曲安奈德经皮渗透的特性.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,考察曲安奈德在皮肤不同层的分布情况.结果 曲安奈德的24h透过量去角质层皮肤约为完整皮肤的1.6倍;8h...     

角质层与活性皮肤层对硝酸异山梨酯透皮吸收的影响

目的:评价皮肤角质层和真皮层对药物经皮吸收的影响。方法:以硝酸异山梨酯(ISDN)为模型药物,采用Franz吸收池法,考察药物单独或与吸收促进剂肉豆蔻酸异丙酯(IPM)合用时,经完整皮肤和角质层剥离皮肤的透皮能力。结果:IS-DN经剥离角质层皮肤的表观透皮系数的Kp是经完整皮肤的1.68倍,IPM能分布在活性皮肤层,并可明显增加ISDN在角质层或真皮层的分布量及经皮累积透皮吸收百分率。结论:本实验为研究皮肤病态条件下(如皮肤受伤或溃疡等),药物透皮吸收规律,提供了一种新的方法。     

高良姜素的体外透皮吸收特性研究

目的:考察高良姜素的体外透皮吸收特性及不同促透剂对其透皮行为的影响,为开发以高良姜素为原料药的治疗白癜风的皮肤给药制剂提供参考。方法:采用高效液相色谱法测定高良姜素的含量。以高良姜素的累积透过量(Q)和透皮速率(J)为指标,考察接收液[20%、40%聚乙二醇400(PEG400)溶液和30%乙醇溶液]、转速(200、300、400 r/min)对高良姜素在小鼠完整皮肤中吸收的影响,考察氮酮(1%、3%、5%)、丙二醇(10%、20%、40%)单用或者联用对其促透作用。同时,考察高良姜素在大鼠和小鼠的完整皮肤、去角质层皮肤、真皮层皮肤的透过特性。结果:以接收液为40%PEG400溶液、转速为300 r/min、5%氮酮单用时,高良姜素在小鼠完整皮肤中的透过性最好,J为3.257 0μg/(cm2·h)。小鼠完整皮肤、去角质层皮肤、真皮层皮肤的J分别为2.7199、34.016、33.874μg/(cm2·h),大鼠3种皮肤的J分别为0.499 6、9.512 4、17.406μg/(cm2·h)。结论:高良姜素可以透过小鼠和大鼠的完整皮肤,但是透过量远低于去角质层皮肤和真皮层皮肤。     

花椒毒素在人体皮肤及角质层中的渗透动力学探讨

目的探讨花椒毒素在人体完整皮肤及其角质层中的渗透动力学特性。方法采用人体离体皮肤及从完整皮肤中分离出的角质层，在Franz-cell扩散池中进行不同浓度的花椒毒素乙醇溶液(0.1, 0.5, 2.5和5.0 mg·mL^-1)的渗透实验，均采用1.4%的人血清溶液作为接收液，用HPLC法测定各接收液的药物量和皮肤中的贮存药物量。结果花椒毒素乙醇溶液单位面积透过完整人皮肤速率随着浓度增加而增加，2.5 mg·mL^-1以上的浓度对其速率几乎无影响。在角质层中也存在同样的现象，但其单位面积透皮速率最大值提前了约6 h。而且随着给药浓度的增加，24 h后完整皮肤和角质层的药物贮存量也相应增加，但达到一定浓度后存在饱和现象。且花椒毒素乙醇溶液在完整皮肤中的透皮时滞(0.82 h)明显大于在角质层中的透皮时滞(0.47 h)。结论该结果对开发花椒毒素外用制剂时浓度的选择提供了依据，并对其外用药物后照射长波段紫外光(UVA)的时间提供了参考。     

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...     

氢醌经不同皮肤层的吸收差异

目的 :评价皮肤角质层和真皮层对药物经皮吸收的差异。方法 :选择氢醌 (HQ)为模型药物 ,采用Franz吸收池法 ,考察药物经完整皮肤和剥离角质层皮肤的体外透皮能力Kp ,并比较吸收促进剂肉豆蔻酸异丙酯(IPM)共存时的促透能力大小。结果 :HQ经剥离角质层皮肤的Kp 是经完整皮肤的3 29倍 ,加入IPM后HQ的Kp 分别提高到原来的4 95倍 (经完整皮肤 )和7 49倍 (经剥离角质层皮肤 )。结论 :本实验为皮肤病态条件 ,如皮肤受伤或溃疡等时的药物经皮吸收规律研究提供了一种新的方法。     

盐酸多塞平乳膏的经皮渗透性比较研究

目的:对比两种盐酸多塞平乳膏的体外透皮特性。方法:建立反相高效液相色谱法测定盐酸多塞平含量;以小型猪皮肤为屏障,改良Franz单室扩散池为体外模型,进行体外经皮渗透实验,求算累积透过量,并测定药物在皮肤的贮留量和剩余量。结果:盐酸多塞平检测浓度的线性范围为0.010 01～0.800 8μg(r=0.999 8),方法准确简单,重复性好;两种乳膏24 h内的皮肤透过量接近(尤其是4 h内几乎重合),在皮肤中的贮留量也相近,药物透皮后均未发生构型的转化。结论:预测两种药品的药效和安全性基本一致。     

氨甲环酸纳米乳膏的制备及体外透皮效果评价

目的设计制备氨甲环酸纳米乳膏(TA-NC),并观察其体外透皮效果。方法采用高压均质法制备氨甲环酸纳米乳,并进一步制得TA-NC,检测TA-NC粒径、微观结构及包封率。以裸鼠皮肤为模型,通过体外透皮吸收实验、离体皮肤组织滞留实验考察TA-NC的体外透皮效果;以尼罗红为荧光探针制备荧光标记TA-NC,共聚焦显微镜观察其促透进入真皮层的效果。并考察TA-NC的6个月加速稳定性。结果制备的TA-NC粒径为(109.9±7.4)nm,形态圆整,分布均匀;包封率为(90.13±2.90)%。体外透皮吸收实验中,TA-NC组给药6 h药物皮肤中的累积滞留量达饱和状态,24 h累积透过量达(163.9±7.4)μg·cm-2;TA水溶液组皮肤的滞留量在20μg·cm-2以下,24 h累积透过量为(15.9±0.8)μg·cm-2,组间差异非常显著(P<0.01)。共聚焦显微镜下,荧光素TA水溶液组仅表皮角质层有荧光,荧光标记的TA-NC经皮吸收后可透过角质层和表皮层到达真皮层,且TA-NC粒径越小透皮能力越强。6个月内TA-NC制剂外观性状、有关物质、含量、粒度等均未发生明显改变。结论 TA-NC制备简单,透皮效果显著,稳定性好。     

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.     

Influence of skin thickness on the in vitro permeabilities of drugs through Sprague-Dawley rat or Yucatan micropig skin

The purpose of this study was to clarify the influence of skin thickness on the in vitro permeabilities of 3 model drugs with different physicochemical properties (nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP)) through Sprague-Dawley rat (rat) or Yucatan micropig (YMP) skin. Intact, dermis-split, stratum corneum-stripped or stratum corneum-stripped and dermis-split rat or YMP skin (rat skin thickness: approximately 0.4, 0.9 or 1.2 mm; YMP skin thickness: approximately 0.4, 0.9, 1.8 or 2.8 mm) were set in Franz-type diffusion cells to determine the permeation rate, lag time and resistance ratio of the viable epidermis and dermis against whole skin (R(ved)/R(tot)) of the drugs. The YMP skin permeabilities of the drugs decreased with an increase in the skin thickness, and significant differences were observed in the permeation rates and lag times between intact and dermis-split (0.4 mm) YMP skins. The decreases in the permeabilities of the drugs through the YMP skin were larger than those through the rat skin. The influence of resistances of ISDN and FP through the dermis-split rat or YMP skin was greater at 0.9 mm skin thickness than 0.4 mm skin thickness. The R(ved)/R(tot) values for the YMP skins were relatively large for lipophilic drugs (ISDN and FP), and these ratios increased with an increase in the dermis thickness. These results suggest that in vitro skin permeation studies must be done using dermis-split (0.4 mm) skin with the thinnest dermis for predicting in vivo human percutaneous absorption rate.     

Topical bioavailability of triamcinolone acetonide: effect of occlusion

BACKGROUND/AIMS: Occlusion by covering the skin with an impermeable wrap enhances skin hydration, affects drug absorption and can induce the formation of a drug reservoir within the stratum corneum. This is desired in local therapy with topical corticosteroids. The aim of the study was to investigate the effect of occlusion before (experiment 1) and after (experiment 2) application on the penetration of triamcinolone acetonide (TACA) into the stratum corneum. METHODS: The experiments were conducted on the forearms of 10 healthy volunteers. In experiment 1, 100 microg/cm(2) TACA in acetone were applied on 3 sites per arm, one arm having been pre-occluded for 16 h. In experiment 2, the same dose was applied on 2 sites per arm, and one arm was occluded after application until skin sampling. Stratum corneum samples were removed by tape stripping at 0.5, 4 and 24 h (experiment 1) and 4 and 24 h (experiment 2) after application. Corneocytes and TACA were quantified by ultraviolet-visible spectroscopy and HPLC, respectively. The total TACA amount penetrated into the stratum corneum was evaluated by multifactor ANOVA. RESULTS: TACA penetration into the stratum corneum with and without pre-occlusion (experiment 1) showed no significant difference and decreased with time. Occlusion after application (experiment 2) produced a marked TACA accumulation within the stratum corneum, which persisted for 24 h. CONCLUSION: Pre-occlusion showed no effect on the topical bioavailability of TACA in the stratum corneum. In contrast, post-occlusion enhanced the TACA penetration by a factor of 2, favouring the development of a drug reservoir.     

Penetration enhancing effect of Azone on the transport of 5-fluorouracil across the hairless rat skin

The effect of the penetration enhancer, Azone, on drug transport across skin was investigated using an in vitro permeation technique involving diffusion cells, hairless rat skin and 5-fluorouracil. The permeability of 5-fluorouracil across full-thickness skin (stratum corneum to dermis transport) was enhanced by Azone about 100-fold although a lag time of approximately 10 h was observed. This long lag time was not found after in vitro and in vivo pretreatments with Azone. Azone had no effect on the epidermis-to-dermis transport (across stripped skin) or dermis-to-stratum corneum transport (across reversed full-thickness skin). These results suggest that the amount of Azone in the skin, especially in the stratum corneum, may be related to its penetration enhancing effect. The results also suggest that incorporation of Azone into transdermal dosage forms could be useful in enhancing the transport of drugs for which the rate-limiting step for percutaneous absorption is penetration of the stratum corneum.     

Promoting mechanism of menthol derivative, 1-O-ethyl-3-buthylcyclohexanol, on the percutaneous absorption of ketoprofen

Menthol derivatives were synthesized and evaluated for their promoting activity on the percutaneous absorption of ketoprofen and skin irritation in vivo, choosing O-ethylmenthol (MET) as the mother compound. The compound having a C-3 positionned n-butyl group (1-O-ethyl-3-n-buthylcyclohexanol, OEBC) indicated the most promoting activity and caused relatively little skin irritation. In order to understand enhancement mechanism of OEBC an in vitro permeation study of ketoprofen was performed. The time course of the cumulative amounts of drug permeated through the rat skin exhibited a linear relation after an initial lag time. This was analyzed in membrane diffusion model and the diffusion and partition parameters of ketoprofen were estimated. Both parameters were remarkably enhanced when a hydrogel containing a small quantity of OEBC (0.5%) was applied. Furthermore, to clarify the site of action of OEBC, we also investigated in vitro permeation study of ketoprofen employing different skins of state, reversed skin and stratum corneum stripped skin. When OEBC was added to the hydrogels which were applied to the reversed and stripped skins, almost no changes of the flux were observed compared with the control (without OEBC). These results suggested that the site of action of OEBC was stratum corneum. Morphological changes of the stratum corneum surface were microscopically observed with 0-2% OEBC. The spaces between the stratum corneum cells treated with 0.5-2% OEBC became extended and the shape of each cell became clear. This may suggest that the site of action of OEBC was the intercellular of stratum corneum. Furthermore, an electron spin resonance study was performed to investigate the effect of OEBC on the intercellular lipid bilayer fluidity of the stratum corneum and the rotational correlation times were calculated. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were used as the spin label. In use of OEBC, the fluidity of TEMPO labeled the stratum corneum lipid increased as the addition of OEBC. The results suggested that OEBC promote the penetration of drugs by enhancing fluidity of the local lipid bilayers around TEMPO.     

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。     

Assessment of the percutaneous penetration of cisplatin: The effect of monoolein and the drug skin penetration pathway

It was intended to examine the in vitro penetration of cisplatin (CIS) through porcine skin in the presence of different concentrations of monoolein (MO) as well as to verify the main barrier for CIS skin penetration. In vitro skin penetration of CIS was studied from propylene glycol (PG) solutions containing 0%, 5%, 10%, and 20% of MO using Franz-type diffusion cell and porcine ear skin. Pretreatment experiments with MO and experiments with skin without stratum corneum (SC) were also carried out. Skin penetration studies of CIS showed that the presence of MO doubled the drug permeation through the intact skin. However, permeation studies through the skin without SC caused only a small enhancement of CIS permeation compared to intact skin. Moreover, pretreatment of skin with MO formulations did not show any significant increase in the flux of the drug. In conclusion, MO did not act as a real penetration enhancer for CIS, but it increased the drug partition to the receptor solution improving CIS transdermal permeation. The absence of improvement in drug permeation by MO pretreatment and by the removal of SC indicates that the SC is not the main barrier for the permeation of the metal coordination compound.     

盐酸尼卡地平贴剂的制备及体外透皮释药

目的：制备盐酸尼卡地平透皮贴剂,研究其释药影响因素。方法：利用Ｆｒａｎｚ扩散池,进行离体皮肤体外渗透实验,通过改变皮肤的状态,研究其体外透皮释药。结果：盐酸尼卡地平贴剂中药物的渗透可用Ｈｉｇｕｃｈｉ方程来表达,去除角质层皮肤的药物渗透远大于完整皮肤,而完整皮肤的贮库效应大于去角质层皮肤。结论：盐酸尼卡地平在经皮渗透过程中存在贮库效应,渗透的主要屏障为角质层。