改善美洛昔康体外经皮渗透的研究

目的:研究几种常用促渗剂对美洛昔康体外经皮渗透的影响,改善美洛昔康体外经皮.方法:用紫外分光光度法检测浓度,采用改进Franz扩散池,比较几种常用促渗剂对美洛昔康渗透速率的影响.结果:氮酮(Azone)单独使用不能明显提高美洛昔康的渗透速率(P>0.05),而丙二醇.薄荷醇、丙二醇 Azone(1:1),丙二醇 薄荷醇(1:1)能显著提高美洛昔康的渗透速率(P<0.01).结论:丙二醇、薄荷醇、丙二醇 Azone(1:1)、丙二醇 薄荷肆(1:1)可作为促渗剂用于美洛昔康经皮吸收制剂.     

促渗剂对奥沙普秦经皮渗透的促进作用

目的：考察几种促渗剂对奥沙普秦透皮作用的影响。方法：采取改良Franz直立式释放池,以离体小鼠皮肤为透皮屏障,计算含不同浓度和组合促透剂的奥沙普秦的累积渗透量Q及渗透速率K,结果;含不同促渗剂奥沙普秦的透皮速率有明显差别,其促进强度依次为油酸＞月桂氮Chuo酮＞薄荷脑;混合促渗剂的促渗效果均比单用时有不同程度的提高;丙二醇有明显的抑制作用,并且抑制油酸,月桂氮Chuo酮及薄荷脑的促渗作用。结论：奥沙普秦透皮吸收符合非极性通道释放的零级动力学方程,其中以10％油酸加1％月桂氮Chuo酮组成的混合促进剂作用最显著。     

奥沙普秦体外渗透性的研究

目的研究不同促渗剂对奥沙普秦渗透性的影响.方法采用Valia-Chien扩散池进行大鼠离体皮肤的体外渗透实验.结果1%氮酮、3%氮酮、10%油酸均具有极显著的促渗作用(P<0.01),5%油酸具有显著的促渗作用(P<0.05),而薄荷油的促渗作用不明显(P>0.05),其中以3%氮酮的促渗效果最好.结论奥沙普秦经皮渗透符合零级动力学过程,不因促渗剂的加入而改变.     

不同促渗剂对盐酸芦氟沙星体外经皮渗透的影响

目的　研究几种常用促渗剂对盐酸芦氟沙星体外经皮渗透的影响。方法　用紫外分光光度法检测浓度 ,采用改进Franz扩散池 ,比较几种常用促渗剂对盐酸芦氟沙星渗透系数的影响。结果　1%氮酮和 1%氮酮 10 %丙二醇可显著增大盐酸芦氟沙星的渗透系数 (P <0 .0 1)。结论　 1%氮酮和1%氮酮 10 %丙二醇可作为促渗剂用于盐酸芦氟沙星的透皮吸收制剂     

水凝胶型小儿退烧微型灌肠剂促渗剂的筛选

目的:研究冰片、薄荷醇和月桂氮芯卓酮对水凝胶型小儿退烧微型灌肠剂的直肠黏膜渗透性的影响。方法:制备含多组促渗剂的水凝胶型小儿退烧微型灌肠,采用改良的Franz扩散池,用猪直肠黏膜进行体外促渗作用研究,高效液相色谱(HPLC)法测定直肠黏膜给药后指标成分栀子苷的累积渗透量及渗透速率。结果:在多组促渗剂中,以含1%薄荷醇-3%月桂氮卓芯酮组合的促渗剂的促渗效果比较明显,其累积渗透量和渗透速率为2.856mg和0.355mg.h-1。结论:以1%的薄荷醇-3%月桂氮芯卓酮组合的混合促渗剂促渗效果为佳。     

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。     

复方酮康唑凝胶促渗剂的筛选

目的:研究辛酸/癸酸甘油酯(Lab)、丙二醇(PG)以及氮酮(Azone)对复方酮康唑凝胶中酮康唑、硝酸咪康唑透皮行为的影响,筛选最佳促渗剂。方法:采用RYJ-6A型药物透皮扩散实验仪,考察不同浓度的Lab、PG、Azone对复方酮康唑凝胶中酮康唑、硝酸咪康唑透皮行为的影响。结果:3%PG的促渗作用最明显,使复方酮康唑凝胶中酮康唑渗透效果增加了2.004倍,硝酸咪康唑渗透效果增加了1.795倍,差异有统计学意义(P<0.05)。结论:3%PG的促渗效果明显,可应用于复方酮康唑凝胶制剂中。     

促渗剂Azone对几种药物透皮速率的影响

Azone(氮酮)是目前国内外所应用的最好的药物透皮吸收促渗剂之一。本文用~3H-Azone作示踪剂,以离体皮肤体外流通扩散室法,研究了国产Azone对α-细辛醚、硝烟酯和硝酸甘油贴剂中药物渗透速率的影响。实验结果表明,Azone能显著增加上述三种药物的渗透速率,在Azone含量为4.8％时,硝烟酯、硝酸甘油和α-细辛醚的渗透速率分别增加133.7％、82.1％和34.5％,而且增渗作用持久。     

促渗剂促进氨氯地平凝胶剂透皮作用的研究

目的 :研究促渗剂对氨氯地平凝胶剂透皮作用的影响。方法 :采取简单小室法 ,用离体小鼠皮肤进行体外透皮扩散试验 ,计算含不同促渗剂的 2 %氨氯地平凝胶的累积渗透量Q及渗透速率k。结果 :1%～ 5 %薄荷脑、1%～ 5 %氮酮对 2 %氨氯地平凝胶的累积渗透量Q及渗透速率k均显著地提高 (P <0 0 1) ;10 %～ 30 %丙二醇显著地降低 2 %氨氯地平凝胶的Q与k值 (P <0 0 1) ,并明显抑制薄荷脑、氮酮的促渗作用 ;薄荷脑与氮酮的联用则无联合增效作用。结论 :提示薄荷脑、氮酮可作为促渗剂在氨氯地平凝胶剂中单独使用     

薄荷醇酯衍生物对压敏胶分散型贴剂中非甾体抗炎药体外经皮渗透性的影响

制备了含不同非甾体抗炎药(酮洛芬、吲哚美辛和双氯芬酸)及促透剂[月桂氮酮、薄荷醇、庚酸薄荷醇酯(M-HEP)或油酸薄荷醇酯(M-OA)]的压敏胶分散型贴剂。采用双室扩散池,以离体大鼠皮肤为屏障进行体外渗透试验,考察了压敏胶和促透剂的种类对贴剂中药物渗透行为的影响。结果表明,用Duro-TAK 87-4098型压敏胶制备的贴剂中酮洛芬的稳态渗透速率和24 h累积透过量显著高于用其他两种压敏胶(Duro-TAK 87-2677和87-2852)制备的贴剂。各促透剂对酮洛芬促渗透作用依序为:M-HEP>M-OA>薄荷醇>月桂氮酮;对吲哚美辛的促渗透作用依序为:M-HEP>M-OA>月桂氮酮≈薄荷醇;M-OA和月桂氮酮对双氯芬酸有显著的促渗透效果,前者的促渗效果较强,而薄荷醇及M-HEP无促渗透作用。     

6种促进剂对西替利嗪体外经皮渗透的影响

目的 :研究 6种不同的促进剂对西替利嗪体外经皮渗透的促进作用。方法 :用Valia Chien水平扩散池 ,选择了丙二醇、月桂氮芯卓 酮 (azone)、柠烯 (dipentene)、水杨酸甲酯、含 10 %薄荷脑的丙二醇、含 10 %樟脑的丙二醇作为促进剂 ,采用离体SD大鼠腹部皮肤用促渗剂预处理的方式 ,建立以去氯羟嗪为内标的反相离子对高效液相色谱法 ,测定接收液中西替利嗪的含量。结果 :除丙二醇和水杨酸外其余几种促进剂对西替利嗪体外经皮渗透都有显著的促进作用 (P <0 .0 1)。以含 10 %薄荷脑的丙二醇的促渗效果最好。结论 :月桂氮芯卓 酮、柠烯、薄荷脑、樟脑可以作为促渗剂用于西替利嗪经皮吸收制剂     

A new colorimetric assay for studying and rapid screening of membrane penetration enhancers

PURPOSE: This work aims to demonstrate a novel chemical assay for rapid screening and analysis of the mode of action of membrane interaction by penetration enhancers. METHODS: The new bio-mimetic membrane assembly, consisting of supramolecular aggregates of lipids and conjugated polydiacetylene, undergoes visible and quantifiable blue-red color transitions upon interaction with penetration enhancers. RESULTS: The new colorimetric model has been employed to examine various classes of penetration enhancers, including 1-dodecylhexahydro-2H-azepin-2-one (Azone), oleic acid, propylene-glycol, menthol, ethoxyglycol-diethyleneglycol-monoethyl-ether (Transcutol), polysorbate-polyethylenesorbitan-monolaurate (Tween-20), and the drug 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one (Diazepam). The assay enables to evaluate the validity of various observations and hypotheses proposed in previous studies regarding permeation enhancement activities. Our results suggest, for example. that propylene glycol (PG) by itself does not interfere with membranes, but rather exhibits synergistic effect in combination with other penetration enhancers. Similarly, our data demonstrate that Transcutol does not independently interact with membranes. The colorimetric system also indicates that interaction of penetration enhancers with membranes depend upon the lipid phase, as well as the self-assembly properties of the enhancer molecules. CONCLUSIONS: The new biomimetic model membrane system can be applied for rapid screening of the activities of penetration enhancers, and provides insight into the mechanisms of permeability of membrane-active compounds.     

复合透皮促渗剂对氨氯地平的促渗透作用

目的：研究不同透皮促渗剂对氨氯地平混悬液的体外兔皮渗透作用.方法：以30%乙醇为溶媒,分别配制含不同透皮促渗剂的氨氯地平饱和混悬液,采用自制改良Franz’s扩散池测量其对体外兔皮的促渗透作用.结果：促渗剂对氨氯地平均有促渗透作用,不同透皮促渗剂促透作用的大小顺序为：丙二醇＜油酸＜阿佐恩＜阿佐恩＋丙二醇＜油酸＋丙二醇.与不含促渗剂相比,油酸＋丙二醇渗透系统稳态透皮渗透速率约为不含促渗剂的2.7倍.结论：复合透皮促渗剂对氨氯地平有良好的促渗透作用.     

不同促透剂对重组人干扰素α-2b体外透皮特性的影响

目的探讨不同促透剂对重组人干扰素α-2b体外透皮特性的影响。方法配制不同组成及比例的促透剂,采用改良的Franz扩散池装置,以离体家兔兔皮为透皮屏障,采用紫外分光光度法计算重组人干扰素α-2b的累积透皮吸收量。结果不同促透剂均有不同程度的促透作用,其促透作用强弱顺序为3%薄荷脑+3%丙二醇>3%薄荷脑>3%氮酮+3%丙二醇>1%氮酮+1%薄荷脑>1%薄荷脑>3%氮酮+3%薄荷脑>1%氮酮>1%氮酮+3%薄荷脑>3%氮酮+1%薄荷脑>3%氮酮。结论氮酮、薄荷脑、丙二醇均可作为重组人干扰素α-2b的透皮促进剂。     

Effects of penetration enhancers on Shuangwu traumatic formula: In vitro percutaneous absorption and in vivo pharmacodynamic evaluation of an herb medicine

The purposes of this study were to improve the transdermal permeation of the Shangwu traumatic formula by chemical penetration enhancers and to investigate the pharmacodynamic changes of the formula caused by incorporated enhancers. The effects of different enhancers on the transdermal absorption of piperine, the representative component of formula, were investigated by in vitro permeation studies. The tests showed an increasing enhancement effect in the following order: Azone/N-methylpyrrolidone (NMP) > oleic acid > Azone/peppermint oil > Azone/oleic acid > Azone/propylene glycol > Azone > peppermint oil > NMP > propylene glycol. The ratio and the content of the most effective enhancer Azone/NMP were determined subsequently. The results suggested that the most significant penetration enhancement was achieved by 3% (w/w) Azone/NMP (3:7). Furthermore, the in vivo pharmacodynamic responses of the formula suspension with or without Azone/NMP were compared using hot-plate assay and xylene-induced ears edema test as models. The data indicated that the formula had positive effect on analgesis and anti-inflammatory, which can be enhanced with the addition of enhancers.     

透皮促进剂对白花前胡甲素体外经皮渗透的影响

目的:考察透皮促进剂对白花前胡甲素(dl-praeruptorin A,Pd-Ia)体外经皮渗透的影响。方法:采用改进的Franz扩散池,以大鼠离体皮肤为渗透屏障,用高效液相色谱法对Pd-Ia进行含量测定,考察月桂氮酮(Azone)及1%Azone与不同浓度丙二醇(PG)混合物对Pd-Ia透皮吸收的影响。结果:使用Azone对Pd-Ia有促透作用,1%Azone效果较好,平均渗透速率达到4.064μg.cm-2.h-1;1%Azone与15%PG合用促透效果最好,平均渗透速率达到4.889μg.cm-2.h-1,且与单用1%Azone有显著性差异(P<0.05)。结论:1%Azone与15%PG合用时,含0.5%Pd-Ia溶液体外渗透具有最大促透效果,体现出协同作用。     

Synthesis and evaluation of N-acetylprolinate esters - novel skin penetration enhancers

A series of N-acetylproline esters (alkyl side chain length, 5-18) were synthesized and tested for potential skin penetration enhancement activity using modified Franz diffusion cells and hairless mouse skin as the penetration barrier. Benazepril and hydrocortisone were used as model drugs and were applied as saturated solutions in propylene glycol. The enhancers were added at a concentration of 5% (w/v). Drug flux, permeability coefficient and enhancement ratios for permeability coefficient were determined. Azone was used as the positive control. While all the compounds tested increased the skin penetration of hydrocortisone, the 5- and 8- carbon esters had no significant effect on the skin penetration of benazepril. The highest fluxes were obtained with 11, 12, and 18-carbon esters and they were comparable to Azone. There was no significant difference between the fluxes obtained with 2 and 5% (w/v) concentrations of the 12-carbon ester on hydrocortisone permeation. The 16-carbon ester, where ethanol was used as a cosolvent, significantly increased the fluxes of both the drugs compared to the control. Differential scanning calorimetric studies suggested that the enhancers may be acting on the lipids of the stratum corneum and their effect was similar to that of Azone. The membrane/vehicle partition coefficient studies indicated an increase in benazepril partition coefficient with enhancer treatment compared to the control. Maximum flux increase was obtained with the 11 and 12 carbon (alkyl chain length) esters for both benazepril and hydrocortisone. The 18- carbon ester which has a cis-double bond in the alkyl side chain, also increased the flux significantly.     

胰岛素体外透皮特性研究

目的 考察胰岛素透皮吸收特性及透皮促进剂对其透皮行为的影响。方法 通过V-C扩散池，用紫外分光光度法测定胰岛素的透皮吸收动力特性及透皮促进剂的促进作用。结果 胰岛素经离体小鼠、家兔、大鼠和人体皮肤的渗透系数分别为16．37，17．54，8．23和9．15。而氮酮(Azone)、冰片、油酸有明显的促透作用，其中3％的Azone和2％的冰片使渗透系数分别增加了4．9和6．1倍。结论 胰岛素在大鼠皮肤中渗透系数与人体皮肤接近，冰片和Azone具有促进药物渗透作用。     

Effect of penetration enhancers on the transdermal delivery of bupranolol through rat skin

Bupranolol (BPL) is a suitable drug candidate for transdermal drug delivery system development based on its favorable physicochemical and pharmacokinetic properties. The effect of different penetration enhancers on the permeation of BPL across rat skin was studied using side-by-side diffusion cells. 2-Pyrrolidone (PY), 1-methyl-2-pyrrolidone (MPY), and propylene glycol (PG) at various concentrations were used as penetration enhancers along with 0.4% w/v aqueous suspension of BPL. Menthol at different concentrations in isopropanol-water (6:4) mixture also was used as an enhancer wherein BPL at 0.4% w/v was completely solubilized. Skin pretreatment studies were carried out with all the above enhancers to understand their role in the penetration enhancement effect. PY and MPY at 5% w/v concentrations increased the permeation of BPL by 3.8- and 2.4-fold, respectively, versus control (p < .01). PG at 10% and 30 w/v concentrations increased the flux of BPL by 2.5- and 5.0-fold, respectively, versus control (p < .001). Menthol at 2% w/v concentration increased the flux of BPL by 3.8-fold (p < .01) and further increase in menthol concentration significantly decreased the flux of BPL. Overall, pyrrolidones and menthol at low concentrations (5% w/v or less) and PG at 30% w/v concentration were effective as penetration enhancers for BPL.