盐酸普鲁卡因经皮离子导入的研究

目的:考察盐酸普鲁卡因的离子导入与电流强度、药物浓度的关系。方法:测定不同的电流强度、不同的药物浓度的离子导入增渗倍数(ER) 。结果:固定药物浓度,电流强度为0 .1 ,0 .2 和0 .3m A 时的ER 值分别为68 ,99和127 。固定电流强度为0 .2m A,药物浓度为0 .0151 ,0 .0304 和0 .0605g/100ml 时的ER 值分别为95 ,99 和98 。结论:离子导入可以显著提高药物渗透速率,增渗倍数(ER) 随着电流强度的增加而增加,但与药物浓度无关     

盐酸利多卡因经皮电离子导入的实验研究

目的：直流电经皮离子导入对局麻药盐酸利多卡因经过兔腹部皮肤的渗透进行研究。方法：采用不同的电流强度以考察电流强度对药物经皮转运的影响。结果：在电流强度分别为０．２５、０．５０和０．８０ｍＡ的条件下，盐酸利多卡因的透皮速率为１．１±０．４ｍｇ·ｈ－１·ｃｍ－２、１．４±０．５ｍｇ·ｈ－１·ｃｍ－２和２．５±０．８ｍｇ·ｈ－１·ｃｍ－２，分别是药物被动扩散透皮速率的３．５倍、４．２倍和７．８倍。结论：经皮离子导入可促进盐酸利多卡因的渗透     

月桂氮Zhuo酮和离子导入对非甾体抗炎药经皮渗透的协同作用

考察了离子导入和月桂氮Ｚｈｕｏ酮预处理以及两法合用对４种非甾体抗炎药吡罗昔康，吲哚美辛、萘普生，双氯芬酸钠体外经皮渗透的促进作用。对４种药物的离子导入增渗倍数分别为３７．２、０．７、６．４和７．５，合用月桂氮酮增渗倍数分别增达９７．２、２０．２、１７．０和１２．１，说明两法合用具协同作用，且对解离型药物促渗作用更强。     

月桂氮酮和离子导入对非甾体抗炎药经皮渗透的协同作用

考察了离子导入和月桂氮酮预处理以及两法合用对４种非甾体抗炎药吡罗昔康、吲哚美辛、萘普生、双氯芬酸钠体外经皮渗透的促进作用。对４种药物的离子导入增渗倍数分别为３７．２、９．７、６．４和７．５，合用月桂氮酮增渗倍数分别增达９７．２、２０．２、１７．０和１２．１，说明两法合用具协同作用。且对解离型药物促渗作用更强。     

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     

吡罗昔康离子导入的实验研究

探讨了离子导入和月桂氮酮预处理对吡罗昔康通过离体大鼠皮肤的影响，选用Ｖａｌｉａ－Ｃｈｉｅｎ扩散池和改良的Ｆｒａｎｚ扩散池，得到吡罗昔康饱和液及其膜剂的透皮速率分别为４．８±０．１７和１．０±０．０４μｇ／ｈ·ｃｍ－２，采用电流强度为０．８ｍＡ的离子导入，药物的透皮速率分别增加１１倍和８倍．另外，月桂氮酮预处理合用离子导入能产生协同作用，其透皮速率为单用月桂氮酮与单用电场透皮速率之和的４倍。     

离子导入和促渗剂对布洛劳经皮渗透的影响

探讨了离于导人和促渗剂月桂氮酮、丙二醇、Ｎ－甲基－２－毗咯烷酮预处理对布洛芬饱和溶液通过大鼠皮肤渗透速率的影响。布洛芬饱和液的透皮速率为２３．０７±０．４５ｕｇ／ｈ·ｃｍ２，采用电流强度为０．２５ｍＡ的离子导入，药物的透皮速率增加１．５倍。采用月桂氮酮、丙二醇、Ｎ－甲基－２－毗咯烷酮预处理后药物的透皮速率分别增加８倍、３．５倍和１倍。月桂氮酮预处理合用离于导人和丙二醇预处理合用离子导人能产生协同作用，药物的透皮速率均比单用促渗剂和离于导人之和高。Ｎ－甲基－２－毗咯烷酮预处理合用离子导人无此作用。     

Characterization of subtype of α_1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed

目的：研究去甲肾上腺素（ＮＥ）介导大鼠肠系膜血管床（ＭＶＢ）收缩的α１肾上腺素受体（α１ＡＲ）亚型．方法：用灌流大鼠ＭＶＢ标本收缩功能实验和克隆细胞放射配体结合实验测定α１ＡＲ亚型选择性拮抗剂ｐＡ２和ｐＫｉ,并作相关分析．结果：α１ＡＡＲ选择性拮抗剂ＲＳ１７０５３、ＷＢ４１０１、５ＭＵ及α１ＤＡＲ选择性拮抗剂ＢＭＹ７３７８的ｐＡ２分别为８９８±０２８,９１６±０２０,８．６９±００２和６０３±０２６,Ｓｃｈｉｌｄ作图斜率值与１０差别无显著性．其ｐＡ２值与α１ＡＡＲ的ｐＫｉ相关系数为０９７,与α１Ｂ和α１ＤＡＲ的相关系数分别为０５２和００４．结论：介导外源性ＮＥ收缩大鼠ＭＶＢ的功能性受体为α１ＡＡＲ     

增渗剂和离子导入对尼莫地平体外经皮渗透性的影响

研究了增渗剂和离子导入技术对尼莫地平（ＮＭ）体外经皮渗透性的作用,渗透促进剂如３％和５％月桂氮卓酮及１０％油酸的２０％丙二醇溶液能增加药物的渗透性（Ｐ＜００５）,其增渗比分别为４６６、４３９及１２６４．离子导入技术能够显著增加药物的渗透性（Ｐ＜００１）,渗透比为８０３．同时表明１０％油酸和３％的月桂氮卓酮丙二醇溶液与离子导入并用,渗透比为１５、８５、８９２．     

电穿孔技术促进萘普生经皮渗透的研究

目的：研究电穿孔技术对小分子离子型药物经皮渗透的影响。方法：应用双室扩散池方法研究电穿孔技术对萘普生在离体大鼠腹部皮肤经皮渗透的影响。并与被动扩散和离子导入进行比较。结果：外加电脉冲（指数衰减型脉冲,脉冲幅度为４００Ｖ,电容器电容为２．２ｕＦ,脉冲率为２０ｐｕｌｓｅｓ．ｍｉｎ＾－１,脉冲宽度τ≈６．０ｍｓ）或离子导入（１ｍＡ．ｃｍ＾－２,６ｈ）时,萘普生的渗透速率和累积渗透量均大于被动扩散。外加脉     

In vivo iontophoretic administration of ropinirole hydrochloride

This work explores the possibility of achieving therapeutic levels of the anti-Parkinsonian drug, ropinirole hydrochloride (RHCl), by transdermal iontophoretic delivery. An in vivo study was performed in hairless rats during which RH(+) was delivered at one current intensity (0.58 mA identical with 0.12 mA/cm(2)) and at three different drug concentrations (25, 125, and 250 mM). In vivo RH(+) flux and transport number were deduced from the steady-state plasma concentration values. Plasma concentration profiles and RH(+) transport numbers were independent of the drug donor concentration. The average iontophoretic input rate was about 3 micromol/h. Postiontophoresis transepidermal water loss (TEWL) was monitored and biopsies were histologically examined to identify any effects of iontophoresis on the skin. TEWL was elevated only at the anodal sites. TEWL recovery was faster for the "no-drug" control anodal sites, which suggests a combined effect of the drug and current on the skin. In conclusion, (1). the in vivo iontophoretic transport of RH(+) is independent of the drug donor concentration, and (2). iontophoresis can deliver therapeutic amounts of RH(+).     

Pharmacokinetic and local tissue disposition of [14C]sodium diclofenac following iontophoresis and systemic administration in rabbits.

The systemic pharmacokinetics and local drug distribution of sodium diclofenac in skin and underlying tissues was studied. Iontophoresis facilitated local and systemic delivery of diclofenac sodium compared with passive diffusion. The maximum plasma concentration of sodium diclofenac was achieved within 1 h of iontophoresis, and the delivery was proportional to applied current density (371 +/- 141 and 132 +/- 62 microg/L at 0.5 and 0.2 mA/cm(2), respectively). The in vivo delivery efficiency for diclofenac in rabbit was 0.15 mg/mA.h. The concentrations of sodium diclofenac in the skin, subcutaneous tissue, and muscle beneath the drug application site (cathode) were significantly greater than plasma concentrations and concentrations of drug in similar tissues at the untreated sites. The results thus suggest that the cutaneous microvasculature is not always a perfect "sink" and that transdermal iontophoresis facilitated the direct penetration of diclofenac sodium to deeper tissues. No skin irritation was observed up to 0.5 mA/cm(2) current density and 7 mg/mL sodium diclofenac concentration.     

Stability of insulin under iontophoretic conditions

The present study focuses on the physical and chemical stability of insulin under iontophoretic conditions using HPLC, SDS-PAGE, RIA and biological assay. Influence of pH, concentration of insulin, current strength and duration of current application on the stability of insulin was studied. Anodal iontophoresis at pH 7.4 caused more than 80% degradation of insulin, while the degradation was minimal at pH 3.6. The degradation was not influenced by insulin concentration, but increase in current strength above 0.75 mA/cm2 or application of current for 12 h (at 0.5 mA/cm2) led to 80 and 20% degradation respectively. All the samples showed biological activity comparable to intact insulin.     

Examination of barriers and barrier alteration in transscleral iontophoresis

The flux enhancing mechanisms of transscleral iontophoresis are not well understood. The objective of the present study was to investigate the ocular barrier and barrier alterations in transscleral iontophoretic delivery with magnetic resonance imaging (MRI). Experiments involving constant current transscleral iontophoresis of 2 mA (current density 10 mA/cm(2)) and subconjunctival injection were conducted with rabbits in vivo and postmortem and with excised sclera in side-by-side diffusion cells in vitro. The postmortem and in vitro experiments were expected to be helpful in clarifying the importance of vascular clearance and other transport barriers in transscleral iontophoresis. Manganese ion (Mn(2+)) and manganese ethylenediaminetetraacetic acid complex (MnEDTA(2-)) were the model permeants. The results show that pretreatment of the eye with an electric field by iontophoresis enhanced subconjunctival delivery of the permeants to the anterior segment of the eye in vivo. This suggests that electric field-induced barrier alterations can be an important absorption enhancing mechanism of ocular iontophoresis. Penetration enhancement was magnified in the postmortem experiments with larger amounts of the permeants delivered into the eye and to the back of the eye. The different results observed in the in vivo and postmortem studies can be attributed to ocular clearance in ocular delivery.     

Iontophoretic transdermal delivery of ketoprofen: effect of iontophoresis on drug transfer from skin to cutaneous blood

The objectives of this study were to develop a method for kinetic analysis of drug transfer to cutaneous blood flow and to evaluate the effect of iontophoresis on drug transfer to cutaneous blood. Cathodal iontophoresis of ketoprofen (non-steroidal anti-inflammatory drug) was conducted to rats (applied electrical current 0.14 and 0.70 mA/cm2; application time 5, 15, 30, 60 and 90 min), and the drug concentrations in skin, cutaneous vein and systemic vein were determined. Transfer rate of ketoprofen from skin to cutaneous blood (R(SC)) was calculated by modifying a physiological pharmacokinetic model. The time-course of R(SC) for 0.70 mA/cm2 showed that the value of R(SC) was initially increased, following a gradual decrease with time after 30-min application. The effect of electrical current on drug transfer to cutaneous blood flow was estimated from the comparison to passive diffusion (without electrical current). The R(SC) value at 30-min application was almost proportional to the electrical current, and the enhancement ratio for 0.14 and 0.70 mA/cm2 was 17 and 73, respectively. Consequently, our results suggest that the change of drug transfer to cutaneous blood flow by iontophoresis may depend on the application period and the magnitude of electrical current.     

Influence of asymmetric donor-receiver ion concentration upon transscleral iontophoretic transport

Recent in vitro and in vivo studies have suggested transscleral iontophoresis as a means for non-invasive drug delivery to the eye. However, there remains a lack of information of the iontophoretic transport behavior of the sclera. The objective of the present study was to investigate the effects of permeant concentration upon transscleral iontophoretic transport. Constant current direct current (DC) iontophoresis was conducted with rabbit sclera in vitro at permeant concentration ranging from 0.015 to 1.0 M in the donor chamber without background electrolyte at 0.4-4 mA (current density: 2-20 mA/cm2). PBS (0.15 M) was the receiver solution. Salicylate (SA) and tetraethylammonium (TEA) were the model ionic permeants, and mannitol was the neutral probe permeant. Conductivity experiments of SA and TEA solutions were performed to determine the effects of ion concentration upon SA and TEA electromobilities. Model simulations were carried out and compared with the experimental data. It was found that the fluxes of the ionic permeants increased linearly with the electric current but were relatively independent of their donor concentrations. Electric field-induced convective solvent flow (electroosmosis) in the sclera was observed to be from the anode to cathode, suggesting that the sclera is net negatively charge at neutral pH. For the studied permeants, electrophoresis was the main transport enhancing mechanism with electroosmosis as a secondary effect. No significant interaction between the permeants and sclera was observed that significantly altered electroosmosis in the membrane. Under the asymmetric donor and receiver conditions, the transference of the permeants could not be predicted by the concentrations of the ions in the donor and receiver chambers with the assumption of constant electric field in the membrane. The membrane ion concentrations were different from those in the chambers due to the requirement of charge neutrality in the membrane.     

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.     

离子导入对卡托普利透皮吸收的促进作用(英文)

目的:研究离子导入技术对卡托普利透皮吸收的促进作用。方法:应用离子导入技术研究了卡托普利体外透过大鼠离体皮肤的影响因素,并进行了卡托普利水凝胶贴片大鼠在体的试验,测定了血药浓度的变化。结果:离子导入技术可以有效地促进卡托普利的透皮吸收,透皮速率增加约7倍。药物贮库中的各种因素如pH,离子强度,药物浓度和电流强度均影响药物的透皮速率。随着pH的增加,离子强度的减小,药物浓度的增加及电流强度的增加,透皮速率也增加。大鼠在体试验也表明用药1h后血药浓度即可达到坪值(约0.9μg/mL),并在整个试验阶段维持稳定。结论:离子导入可以有效地促进卡托普利的透皮吸收。     

Transdermal iontophoresis of hydromorphone across hairless rat skin in vitro

The feasibility of delivering hydromorphone by transdermal iontophoresis to obtain therapeutically effective analgesic concentrations for the management of cancer-related pain was evaluated. Anodal iontophoresis was performed, and the effect of current strength, current duration, solution pH, presence of buffer ions, and drug concentration on the transdermal permeation of hydromorphone was investigated in vitro. Freshly excised full-thickness hairless rat skin and side-by-side permeation cells connected to the Phoresor II with Ag/AgCl electrodes was used. The flux of hydromorphone was observed to significantly increase (P < 0.05) from 72.04-280.30 microg/cm(2)/h with increase in current strength from 0.10-0.50 mA. A linear relationship was obtained between hydromorphone flux and current strength. Furthermore, the flux of hydromorphone was influenced by solution pH and presence of buffer ions. Also, the in vitro permeation flux of hydromorphone was observed to significantly increase (P < 0.05) with a 10-fold increase in hydromorphone hydrochloride concentration from 0.01-0.10 M. However, with further increase to 0.50 M, there was no significant difference in flux. These results show that by manipulating electronic and formulation variables, the transdermal iontophoretic delivery of hydromorphone can be controlled, and therapeutically effective concentrations of hydromorphone for the management of cancer-related pain can be obtained.     

Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin

The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm² resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel and when combined with iontophoresis it was possible to deliver 10 mg/cm²/day of buspirone hydrochloride.