雷公藤凝胶与软膏中雷公藤内酯的经皮渗透性比较研究

目的：比较雷公藤凝胶剂与软膏剂中雷公藤内酯的经皮渗透性，以及不同浓度氮酮对凝胶剂透皮吸收的影响。方法：采用Franz扩散池法研究雷公藤凝胶与软膏剂中雷公藤内酯的透皮行为，高效液相色谱法测量透过小鼠皮肤的雷公藤内酯的含量。结果：雷公藤内酯在凝胶剂及软膏剂中的透皮符合Fickg定律，透皮速率恒定，体外透皮为零级过程；雷公藤内酯在凝胶剂中的透过速率远大于软膏剂，2．5％的氮酮对雷公藤内酯的经皮渗透性具有较好的促进作用。结论：雷公藤凝胶剂的透皮吸收强于软膏剂，有望开发为一种新的雷公藤外用制剂。     

一种新的促进剂/共促进剂在体外实验提高盐酸吗啡皮肤渗透性

文献证实,同时使用几种透皮促进剂将产生协同作用,促进盐酸吗啡在体外的透皮吸收。本文对一些透皮促进剂:氮酮(3％)、十四烷酸异丙醇酯(5％)、Sefsol-318(5％)、l-薄荷醇(5％)和乙醇(40％)对盐酸吗啡的在体外透皮吸收的影响作了研究,并联合使用一些有不同作用机理的透皮促进剂,以期找到理想的透皮促进剂。体外皮肤渗透性实验:平均体重150g、雄性裸鼠的整皮或去角质层的腹部皮肤分别被用来作皮样。实验时,小心地固定皮样在双室     

月桂氮(艹卓)酮对替硝唑透皮吸收的作用

目的：本文的研究为临床用药和配制替硝唑（ＴＮＺ）外用药选择适宜药物浓度和促进剂浓度提供依据。方法：观察ＴＮＺ对小白鼠离体皮肤的透皮吸收，比较不同药物浓度的透皮吸收量及月桂氮酮（Ａｚｏｎｅ）不同浓度的促渗作用。结果：０．２％，０．４％，１．０％ＴＮＺ，１２ｈ透皮吸收量分别为１．４１，２．８２，７．１２ｍｇ·（５０ｍｌ）－１，渗透系数分别为１２．９８×１０－６，１３．６８×１０－６，１３．７７×１０－６。促渗剂Ａｚｏｎｅ含量在５％以下时，ＴＮＺ透皮吸收百分率随着Ａｚｏｎｅ浓度的提高而增加；当Ａｚｏｎｅ含量达８％时，透皮吸收率反而下降。结论：ＴＮＺ可透过离体小白鼠皮肤，提高药物浓度可增加药物的透皮吸收量。促渗剂Ａｚｏｎｅ用量以２％～５％为最佳     

薄荷醇促皮渗透作用研究

薄荷醇在离体裸鼠皮肤可以明显增加水杨酸和氟脲嘧啶的透皮吸收率。在正常人前臂内侧皮肤增加氟轻松和氯氟舒松经皮吸收，并存在剂量效应关系。在整体兔，使水杨酸经皮肤吸收入血明显增加，其ＣｍａｘＡＵＣ０－１２ｈ分别提高１５１％和８７．２％。提示薄荷醇是一种透皮促进剂。     

透皮吸收促进剂的临床应用

透皮吸收促进剂(简称穿透促进剂)系指可以加快药物穿透皮肤的速度而不对皮肤形成严重刺激和损害的物质。最早主要应用于软膏剂、擦剂、涂布剂等,随着制剂技术的不断发展、外用制剂的剂型不断增加,其用途不断扩大如骨架型透皮释放给药系统、压敏微储库型给药系统、贴布剂等。     

3种吸收促进剂对酮基布洛芬经不同皮肤层渗透的影响

目的：对不同性质的吸收促进剂影响药物经不同皮肤层渗透的差异进行评价。方法：选择氮酮（AZ），肉豆蔻酸异丙酯（IPM）和单月桂酸甘油酯（GML）为透皮促进剂，以酮基布洛芬为模型药物，采用Franz吸收池法，考察药物单儿或与促进剂合用时，完整皮肤和剥离角质层皮肤的透皮能力。结果：剥离角质层皮肤可明显增加酮基布洛芬的透皮层。3种吸收促进剂对药物经完整皮肤的促透能力为IPM＞GML＞AZ，对药物经剥离角质层皮肤的促透能力为GML＞IPM＞AZ。结论：皮肤的条件能明显影响酮基布洛芬的经皮渗透；吸收促进剂对酮基布洛芬经不同皮肤层的促透能力有差异。     

氮酮和薄荷醇对联苯苄唑体外经皮渗透性的影响

目的：研究透皮促进剂氮酮和薄荷醇对外用抗真菌药联苯苄唑体外经皮渗透性影响。方法：在离体透皮实验装置上进行透皮吸收试验和贮库效应的研究，采用正交函数分光光度法消除皮肤浸出物的吸收干扰。结果：1％氮酮明显促进联苯苄唑经皮渗透作用，并可明显缩短时滞而增加贮库效应。结论：氮酮对亲脂性极强的药物联苯苄唑的促透皮吸收作用较强，而薄荷醇无明显的促透作用，但可增加贮库效应。     

以经皮微渗析技术涂抹表皮生长因子的小猪在体经皮吸收研究

目的研究表皮生长因子的经皮渗透性，并考察透皮吸收促进剂月桂氮酮（Azone）对其经皮渗透性的影响。方法以广西小型猪为实验模型动物，应用经皮微渗析在体取样技术进行实验。探针的在体回收率以反向渗析法测定。结果Azone可以极人地提高药物在渗析液及皮肤中的浓度，2％和5％的Azone分别使渗析液中药物的稳态流量从0.001μg/h提高到1．281和1．824μg／h。结论经皮微渗析技术是研究药物在体经皮吸收的有力工具。Azone是表皮生长因子经皮吸收的优良促进剂。     

透皮促进剂在经皮给药系统中的应用近况

透皮促进剂是指所有能够增加药物透皮速度而对皮肤不造成严重刺激和损害的物质。近年来 ,经皮给药系统的基础实验取得了可喜进展 ,透皮制剂的组方及用现代方法对药物在体内或体外透皮吸收进行较系统的研究成绩显著。经皮给药的理论基础为给药后 ,药物能迅速穿透皮肤 ,被吸收进入血液循环而产生疗效。因此 ,研究经皮给药制剂时首先必须解决药物对皮肤的穿透性和透皮速率。目前的技术多采用添加月桂氮酮(Ａｚｏｎｅ)、亚油酸、丙二醇 (ＰＧ)等透皮促进剂来增加药物的穿透性和提高药物的透皮速率。在应用这些促进剂时 ,研究者又发现按一定比…     

促透剂在透皮吸收制剂中的应用概况

目的为透皮吸收制剂的研究与开发提供信息参考。方法查阅近年来国内外透皮吸收制剂研究论文，总结10种透皮吸收促进剂的研究报告。结果透皮吸收促进剂在透皮吸收制剂研究中的合理选择是影响药物透皮吸收的一个关键因素。结论透皮吸收促进剂在药物透皮吸收制剂研究和新药开发中有着广泛的应用前景。     

Differences in penetration-enhancing effect of Azone through excised rabbit, rat, hairless mouse, guinea pig and human skins

The transdermal delivery of dihydroergotamine (DHE), from propylene glycol formulations with and without 6.0% laurocapram (Azone), and the penetration enhancing effect of Azone were evaluated in vitro on excised rabbit, rat, hairless mouse, guinea pig and human skins utilizing improved Franz diffusion cells. The steady-state flux of DHE from the propylene glycol formulation without Azone were 0.045, 0.270, 0.395, 0.128 and 10.035 μg/cm² per h across excised human, rat, guinea pig, rabbit and hairless mouse, respectively. Under the influence of the enhancer, Azone increased DHE penetration through excised skin of the various species used in this study in the following order: rabbit skin > human skin > rat skin > guinea pig skin > hairless mouse skin. The maximum enhancement factor of Azone (251.47) was obtained across rabbit skin and the minimum enhancing effect (14.44) was observed in the case of hairless mouse skin. The enhancement factor of Azone across human skin was 54.56. These results show that animal skins are poor models for human skin under the conditions used. The lag time of DHE, from the propylene glycol formulation containing 6.0% Azone, through human skin was longer than the lag times across all other skin species tested in this investigation.     

Enhanced penetration of mitomycin C through hairless mouse and rat skin by enhancers with terpene moieties

The effects of four new percutaneous absorption enhancers containing an azacyclo ring and terpene chain (1-geranylazacycloheptan-2-one (GAH), 1-farnesylazacycloheptan-2-one (FAH), 1-geranylazacyclopentan-2,5-dione (GAPD), and 1-farnesylazacyclopentan-2-one (FAP] and 1-dodecylazacycloheptan-2-one (Azone) on the percutaneous penetration of mitomycin C (MMC) through hairless mouse and rat skin in-vitro has been investigated. GAH, FAH, FAP and Azone enhanced MMC penetration by 20 to 60 times that of the control (ethanol). During the early part of the experiments, when the sink condition was maintained, FAH was the most effective for hairless mouse skin, whereas Azone showed the highest effect in the rat skin. The enhancing effect of GAPD was only about half that of the other enhancers, suggesting the importance of the polar group of the ring moiety in these compounds. The penetration of MMC through rat skin was also increased by pretreatment with these compounds, suggesting that the enhancers had a direct effect on the skin.     

Azone预处理对抗病毒药Ara-ADA穿透无毛小鼠皮肤的持续影响

本文用两个半池组成的扩散池测定4～6周无毛小鼠腹部皮肤用1-十二烷基氮杂环庚烷2酮(Azone)预处理24h后,对抗病毒药2′,3′-双乙酰阿糖腺苷(2′,3′-di-O-acetyl-3-βD arabinofuranosyl adenine简称Ara ADA)透过皮肤促进作用的持续效应。皮肤经Azone处理后,立即或分别测定经历4,5…8d后的穿透系数。结果表明,经Azone处理后的无毛小鼠皮肤可使Ara ADA的穿透系数提高44倍,皮肤经Azone处理一次后,药物透过皮肤的促进作用至少可持续8d,药物通过皮肤的扩散时滞明显缩短。     

Influence of 1-dodecylhexahydro-2H-azepin-2-one (Azone) on the in vitro permeation of verapamil hydrochloride across rat, hairless mouse, and human cadaver skin

The effect of 1-dodecylhexahydro-2H-azepine-2-one (Azone; laurocapran; 1) on the permeation of verapamil hydrochloride (2) through rat skin was studied. Compound 1 was used in various concentrations in the donor phase. The permeation of the drug increased significantly in the presence of 1 and the enhancement in permeation was dependent on the concentration of 1. A comparison of the enhancing effect of 3% 1 on permeation of 2 through rat, hairless mouse, and human cadaver skin was made. Compound 1 altered the permeability of hairless mouse skin significantly, whereas the effect on rat and human skin was comparable and not very drastic.     

In vitro evaluation of a series of azone analogs as dermal penetration enhancers: III. Acyclic amides

A scries of acyclic amides was synthesized and tested for enhancement properties using excised hairless mouse skin and hydrocortisone 21-acetate as the model drug. All compounds were applied at 0.4 M (or at their respective saturation solubilities) in propylene glycol. Azone (0.4 M) was used as a standard enhancer. Enhancement ratios were calculated for flux, 24 h diffusion cell receptor concentrations (Q₂₄) and 24 h full-thickness mouse skin steroid content. Enhancer 5 showed the highest activity for flux (35.22-fold over control), 24 h receptor concentration (79.86-fold over control) and skin drug content (4.3-fold over control). These enhancement ratios were higher than those for Azone which were 19.51, 38.30 and 1.5-fold over control, respectively. Enhancers 4, 10 and 11 showed similar Q₂₄ values to Azone, and 3, 9 and 10 increased skin steroid content to a greater extent than Azone.     

Cutaneous Metabolism of Nitroglycerin in Vitro. II. Effects of Skin Condition and Penetration Enhancement

The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4°C did not alter barrier function to total nitrate flux [GTN + 1,2-glyceryl dinitrate (1,2-GDN) + 1,3-glyceryl dinitrate (1,3-GDN)]. However, metabolic function was significantly impaired and suggested at least fivefold loss of enzyme activity. Heating skin to 100°C for 5 min appreciably damaged hairless mouse skin barrier function. The ability to hydrolyze GTN was still present, however, and remained constant over the 10-hr experimental period, in contrast to the control, which showed progressively decreasing enzymatic function with time. Pretreatment of hairless mouse skin in vivo (prior to animal sacrifice, tissue excision, and in vitro transport/metabolism studies) with 1-dodecylazacyclo-heptan-2-one (Azone), a putative penetration enhancer, significantly lowered the skin barrier to nitrate flux (relative to the appropriate control). Again, barrier perturbation resulted in essentially constant metabolic activity over the observation period. The ratio of metabolites formed (1,2-GDN/1,3-GDN) was increased from less than unity to slightly above 1 by the Azone treatment. Adhesive tape-stripping gradually destroyed skin barrier function by removal of the stratum corneum. The effects of 15 tape-strips were identical to those of Azone pretreatment: a greatly enhanced flux, a constant percentage formation of metabolites over 10 hr (once again), and an increase in the 1,2-GDN/1,3 GDN ratio. Overall, the experiments caution that, for transdermal drug delivery candidates susceptible to skin metabolism, the status of barrier function (enhancer pretreated, skin damage or disease, etc.) may significantly affect systemic availability.     

Effect of the absorption enhancer, Azone, on the transport of 5-fluorouracil across hairless rat skin

The effect of the percutaneous absorption enhancer, Azone, on the transport of 5-fluorouracil across hairless rat skin has been investigated by an in-vitro permeation technique using 2-chamber diffusion cells. Azone (3% w/v) emulsions were used. Azone enhanced the permeability of drug 10-100 times across the full-thickness skin although there was a lag time about 10 h. The long lag time, however, disappeared with Azone pretreatment. Azone also affected the transport across stripped skin. These results suggest that Azone mainly affects the stratum corneum. It seems to change the diffusivity of drug in that layer and is not so effective against diffusivities in the epidermis and dermis.     

In vitro evaluation of a series of Azone analogs as dermal penetration enhancers: IV. Amines

Dermal enhancement properties of 12 novel amine enhancers (Azone analogs) were studied using in vitro diffusion cell techniques. Standard enhancers tested were Azone, didodecylamine, dodecylamine, and stearylamine. The synthesis of these novel compounds is presented. Hydrocortisone 21-acetate was used as the model drug and its transdermal permeation and skin retention were examined using hairless mouse skin. Enhancement ratios (ER) were determined for flux, 24 h diffusion cell receptor concentrations (Q24), and 24 h full-thickness skin steroid content. ER for all parameters for control was 1.00. Control was no pretreatment of the skin. All enhancers were applied at 0.4 M in propylene glycol 1 h prior to steroid application. N-dodecyldiethanolamine showed the greatest Q24 value (ER 56.16) while N-(2-methoxyethyl)dodecylamine showed the greatest skin retention (ER 2.0). Azone ER values were Q24 38.30 and skin retention 1.5, and those for didodecylamine were 13.06 and 1.1, respectively. In general, tertiary cyclic amine and secondary amine enhancers showed less activity for flux than the tertiary acyclic amine compounds.     

Percutaneous Penetration of Acyclovir Through Excised Hairless Mouse and Rat Skin: Effect of Vehicle and Percutaneous Penetration Enhancer

The effects of vehicle and percutaneous penetration enhancer on the penetration of acyclovir through excised hairless mouse and rat skin were investigated. Four solvents, propylene glycol (PG), ethanol (ET), isopropanol (IPA), and isopropyl myristate (IPM), were employed as vehicles, in combination with four enhancers, l-farnesylazacycloheptan-2-one (7FU), l-geranylazacycloheptan-2-one (7GU), l-geranylazacyclopentan-2-one (5GU), and l-dodecylazacycloheptan-2-one (Azone). Acyclovir was suspended in vehicles to avoid the effect of the thermodynamic activity of acyclovir in the vehicle. The penetration of acyclovir through hairless mouse skin from IPA was enhanced by 7GU, whereas that from IPM was not affected. All combinations of vehicle and penetration enhancer were examined using rat skin. No effect of the enhancers was observed in the IPM vehicle. The estimated solubility parameters of vehicles and enhancers indicated that the polarities of IPM and the enhancers are similar, which prevents effective penetration of the enhancers from IPM. However, the penetration of acyclovir from the other vehicles was increased by the enhancers. The combination of hydrophilic vehicle and hydrophobic enhancer resulted in a large enhancing effect. The disappearance of the enhancers from the vehicle correlated with their enhancing activity, but other factors also seemed to affect the penetration enhancement of acyclovir.