芬太尼离子导入给药装置自控镇痛与癌痛治疗

芬太尼离子导入给药装置(ITS)患者自控镇痛(PCA)实现了无损伤给药和自控给药,对术后急性疼痛的控制效果满意,可能对癌痛治疗也会发挥较好的镇痛效果.本文重点介绍离子药物导入技术、芬太尼ITS、经皮芬太尼主动和被动转运给药药代动力学.     

药物导入治疗仪佐治小儿肺炎的疗效观察

目的探讨药物导入治疗仪佐治小儿肺炎的疗效。方法对100例小儿肺炎进行临床随机分为治疗组和对照组,每组50例。对照组给单一抗生素加抗病毒药物治疗。治疗组在对照组基础上采用药物导入治疗仪辅以经皮给药治疗。结果治疗组总有效率、退热时间、治愈时间、肺部啰音消失时间均优于对照组（P〈0.05或P〈0.01）。结论结合药物导入治疗仪佐治小儿肺炎起效快、药效强、缩短病程、疗效满意。     

超声促进药物进入人体

<正> 超声波促进药物经皮导入尚未被药政机构确定为一种专门的方法,但至少有30％的理疗师已在使用。经皮药物导入在方便的部位施行,可以针对全身或局部的靶组织,但是物药进入皮肤和血管都会有某种程度的全身影响。 药物经皮导入的主要障碍是皮肤,电导     

药物电离子导入的新进展

<正> 由于药物经皮释放系统(TransdermalDelivery System)的给药方式有许多优点,所以被开发研究。但发现很多药物不能以一定的速率经皮给药,使获得有效的血药浓度。因此,经皮释放系统的临床应用,尚受到一定的限制。为降低皮肤的阻力,提高经皮给药的血药浓度,近年来,不少学者又深入研究药物电离子导入疗法,并取得了新进展,使这个古老的给药方式,将成为医药界今后重点研究的课题。(一)体外实验模型的设计:体外实验模型,近来也有很大的改进。一般分给药室(Donor cell)和接受室(Recep-     

透皮给药系统在镇痛治疗中的临床应用和治疗进展

<正>近年来透皮给药系统以其无需针刺、避免了胃肠道反应、提高了生物利用度等优势被广泛研究。而为了保证镇痛治疗的持续性和有效性,出现了采用透皮给药系统促进止痛药物经皮吸收的新型方法。本文对直流电离子导入技术和超声透皮给药技术促进镇痛药物经皮吸收展开论述,探讨这些技术的安全性和有效性,以及影响药物渗透吸收的因素。传统镇痛常以口服非甾体类抗炎药、局部外用药物或者静脉滴注镇痛药物为主,但分别面临胃肠道反应、镇痛效果有限以及     

影响直流电药物离子导入治疗效果的技术因素

本文综述了影响直流电药物离子导入治疗效果的技术因素。共有以下12种:①电流:治疗中电流强度发生变化,主要在开机后10分钟内。电流强度的掌握应依年龄、性别、部位、衬垫面积、病种、方法等具体情况而定。②时间:一般为20～30分钟,时间延长,导入量反而减少。③药物浓度:有人测定69种药物电导率,大多数随浓度升高而上升,少数达一定浓度时不再上升,有的反而下降。④药物性质:应掌握药物电离的极性,选定导入的电极。不能电离的药物是不能作直流电导入的,如氢化考的松,醋酸考的松就是非电离型化合物,不宜作电导入。⑤溶剂:二甲基亚砜是万能溶媒,可增加导入量1.5～2倍。黄连素的盐酸盐制剂几乎不溶于水,故不宜作电导入,而应用其硫酸盐或枸橼酸盐制剂。⑥药液的pH值:某些有机化合物属于两性电解质,在不同的pH值溶媒中,带有不同的电荷。不同药物采用阳极、阴极或非极化电极。⑦寄生离子:配制剂时必须用纯水配制,不宜用开水、自来水、河水、井水等配制。导入衬垫必须分别清洗,一药一垫,不可混用,混洗。⑧皮肤状态:去毛后24小时,以摩擦法除去角质层再导入,可使疗效提高。⑨导入电流的种类:平稳直流,平稳加直角脉冲,脉冲直流,半波音频,半波中频,双向交流中频电,文献报告意见不统一。⑩与其它理疗的联合应用:导入前作热疗,导入时作冷敷,可增加导入量。音频电或调制中频与直流电导入同时联合应用可提高导入率。直流电与超声联合应用可提高导入量15%～130%倍。(11)导入方法;眼杯法是衬垫法导入量的16～19倍。离子交换薄膜可提高导入量近3倍。保持衬垫厚度不小于1cm。(12)时律:直流电药物导入宜于上午进行。     

电子导入技术国内外研究近况

电离子导入技术作为一种理疗手段已有 2 0 0余年历史 ,近年来其应用越来越广泛 ,并且随着多肽及核酸等大分子药物的研制 ,该技术逐渐成为一种重要的给药方式。另外 ,利用反向离子导出进行无损伤的体液化学检测也逐渐受到重视。国内电离子导入的应用也很普遍 ,特别是中药离子导入为我国首创 ,已有多篇综述性文献[1- 4] 。我们拟从电离子导入在国外的实验研究历程 ,以及当前的发展前景进行综述。　　 190 0年Ｌｅｄｕｃ引入“电离子导入”(Ｉｏｎｔｏｐｈｏｒｅ ｓｉｓ)这个名词 ,并使电离子导入装置基本成型。他的著名实验 ,将士的宁在 4 0 -…     

药物离子电导入方法在眼科应用的新进展

<正> 眼球由于组织结构的特殊,用药后能否到达眼组织的治疗部位,取决于给药方法和药物本身的理化特性.为此,在研究给药方法时,近年来国外学者利用药物离子电导入方法,进行了大量的动物实验。因为眼角膜是无血管的组织,药物离子进入后,不易马上被血循环带走,可产生较长期的作用:房水     

经皮给药在儿科中的应用概况

经皮给药理论是20世纪80年代国外首先提出的，指药物通过现代化仪器设备以一定的速度通过完整皮肤，进入人体组织后被吸收进入血液循环，从而产生药效的一种治疗方法。而经皮给药治疗术则是90年代末在美国等西方国家兴起的一项新的药物治疗技术，被称为第三代给药治疗方法。近年来，国内已将这一方法应用于儿科疾病的治疗，尤其是呼吸道感染和腹泻的治疗。现将近年来经皮给药在儿科中的运用综述如下：     

经皮电离子中药导入治疗闭合性软组织损伤

目的:探讨中药离子导入治疗闭合性软组织损伤的有效性和安全性。资料来源:应用计算机检索Elsevier SDOL数据库1985/2006与中药离子导入治疗闭合性软组织损伤相关文章,检索词“traditional Chinese medicine ion-introduction,closed soft tissue injury”,并限定文章语言种类为“English”。同时用计算机检索CNKI数据库1994/2006的相关文章,限定文章语言种类为中文,检索词“中药离子导入,闭合性软组织损伤”。资料选择:对资料进行初审,选取试验采用中药离子导入方法治疗闭合性软组织损伤的文献,及与经皮离子导入中药的相关文献。无论是否随机对照均纳入,排除陈旧和综述类文献。资料提炼:纳入30篇符合标准的文献,其中9篇介绍电离子导入的原理和特点,6篇关于导入所用的中药,16篇是临床应用报告。资料综合:所收集资料中的试验包括4265例患者,均采用中药离子导入法治疗闭合性软组织损伤,对其结果予以评价。常用的中药有活血药、理气药、补肝肾续筋骨药、祛风寒湿药和清热药等,其治愈率约为52.6%,显效率约为35.8%。结论:中药电离子导入治疗闭合性软组织损伤已经广泛应用于临床,但是基础研究不足,中药起作用的成分不十分明确,需进一步研究。     

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the varying electric pulse amplitude, the amount of topical and transdermal drug delivery to the skin can be controlled. Furthermore, the newly developed monitoring system provides a tool for rapid real-time determination of both, transdermal and topical delivery, when the delivered molecule is fluorescent.     

聚羟基脂肪酸酯和聚酰胺-胺树状高分子构筑的经皮给药系统

背景：聚羟基脂肪酸化合物具有黏着性及与药物分子混合、分散的特性,可作为体外给药剂型的基质;树状高分子具有独特的物理、化学性质,能够作为药物的载体。目的：将聚羟基脂肪酸化合物与聚酰胺-胺树状高分子混合,构筑能够促进难溶型药物的透皮的经皮给药系统。方法：将恶臭假单胞菌 KT2442在含有NH4Cl的培养基中30℃培养72 h,然后在培养体系中添加5 g/L辛烷酸培养24 h,用氯仿抽提聚羟基脂肪酸化合物。各取10 mg聚羟基脂肪酸化合物基质与含聚酰胺-胺与苯乙胺树状高分子的聚羟基脂肪酸化合物基质,分别与5 mg磺酰胺衍生物Tamsulosin混合,构建经皮给药系统;同时构建体外渗透研究装置,研究基质促进药物渗透的效果。X射线衍射分析Tamsulosin、聚羟基脂肪酸化合物基质、基质聚羟基脂肪酸化合物-Tamsulosin 及含聚酰胺-胺树状高分子聚羟基脂肪酸化合物基质-Tamsulosin的内部原子空间分布状况。结果与结论：聚羟基脂肪酸化合物及聚羟基脂肪酸化合物与聚酰胺-胺树状高分子的混合物都能作为经皮给药的基质,促进难溶药物的透皮作用;并且在相同的条件下,聚羟基脂肪酸化合物与聚酰胺-胺树状高分子的混合物作为基质的经皮给药系统能够满足药物的临床血药浓度。聚羟基脂肪酸化合物与聚酰胺-胺树状高分子的混合物能够使模型药物很好地晶体化并呈现高度有序的方向性。     

Iontophoretic delivery of drugs: Fundamentals,developments and biomedical applications

Iontophoretic drug delivery implies the delivery of ionic (charged) drugs into the body by the use of electric current. The technique is not new and has been used clinically in delivering medication to surface tissues for several decades. However, its potential is recently being rediscovered for transdermal systemic delivery of ionic drugs including peptide/protein drugs which are normally difficult to administer except by parenteral route. The technique has been observed to enhance the transdermal permeation of ionic drugs severalfold, and this can expand the horizon of transdermal controlled drug delivery for systemic medication. However, miniaturization of iontophoretic devices and electrodes and prevention of any possibility of skin burns are required to make this technique useful for biomedical applications. While the literature on iontophoretic systemic drug delivery is relatively recent and not extensive, the published results on clinical usage and other related aspects can be quite informative and could stimulate and assist the readers to explore other biomedical applications. This article is intended to review old as well as very recent literature on the technique, methodology, clinical findings, influencing factors, relevant electronics and other related aspects of iontophoretic drug delivery, and to provide the readers a comprehensive overview of the state-of-art of this potential new area of biomedical research.     

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch

Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.     

The quest for non-invasive delivery of bioactive macromolecules: a focus on heparins.

The development of a non-invasive drug delivery system for unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) has been the elusive goal of several research groups since the initial discovery of this glycosaminogylcan by McLean in 1916. After a brief update on current parenteral formulations of UFH and LMWHs, this review revisits past and current strategies intended to identify alternative routes of administration (e.g. oral, sublingual, rectal, nasal, pulmonary and transdermal). The following strategies have been used to improve the bioavailability of this bioactive macromolecule by various routes: (i) enhancement in cell-membrane permeabilization, (ii) modification of the tight-junctions, (iii) increase in lipophilicity and (iv) protection against acidic pH of the stomach. Regardless of the route of administration, a simplified unifying principle for successful non-invasive macromolecular drug delivery may be: "to reversibly overcome the biological, biophysical and biochemical barriers and to safely and efficiently improve the in vivo spatial and temporal control of the drug in order to achieve a clinically acceptable therapeutic advantage". Future macromolecular drug delivery research should embrace a more systemic approach taking into account recent advances in genomics/proteomics and nanotechnology.     

Controlled transdermal iontophoresis by ion-exchange fiber.

The objective of this study was to assess the transdermal delivery of drugs using iontophoresis with cation- and anion-exchange fibers as controlled drug delivery vehicles. Complexation of charged model drugs with the ion-exchange fibers was studied as a method to achieve controlled transdermal drug delivery. Drug release from the cation-exchange fiber into a physiological saline was dependent on the lipophilicity of the drug. The release rates of lipophilic tacrine and propranolol were significantly slower than that of hydrophilic nadolol. Permeation of tacrine across the skin was directly related to the iontophoretic current density and drug concentration used. Anion-exchange fiber was tested with anionic sodium salicylate. The iontophoretic flux enhancement of sodium salicylate from the fiber was substantial. As the drug has to be released from the ion-exchange fiber before permeating across the skin, a clear reduction in the drug fluxes from the cationic and anionic fibers were observed compared to the respective fluxes of the drugs in solution. Overall, the ion-exchange fibers act as a drug reservoir, controlling the release and iontophoretic transdermal delivery of the drug.     

Palatal mucosa as a route for systemic drug delivery: A review

Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive pre-systemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Historically, oral transmucosal drug delivery has received intensive interest since ancient times for the most widely utilized route of administration for the systemic delivery of drugs. In more recent years, better systemic bioavailability of many drugs has been achieved by oromucosal route. Among the various transmucosal sites available, soft-palatal mucosa was also found to be the most convenient and easily accessible novel site for the delivery of therapeutic agents for systemic delivery as retentive dosage forms, because it has abundant vascularization and rapid cellular recovery time after exposure to stress. Smooth surface of the soft palate and its good flexibility are prerequisites to prevent mechanical irritation and local discomfort. The objective of this review is to provide an update on the most promising advances in novel non-invasive soft-palatal route and the conceptual and technical approaches to the design and formulation of soft-palatal drug delivery systems. In this area, the development of mucoadhesive delivery systems appears to be the most promising strategy.     

Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow--limited percutaneous absorption.

For most drugs delivered by the transdermal route, percutaneous absorption is limited by the rate of release of the drug from the device or by diffusion across the stratum corneum. However, systemic absorption also requires that the drug be taken up by dermal blood vessels. As part of a bioavailability study of a transdermal delivery system, we observed that a concomitant intravenous infusion of nicotine had a marked effect on the absorption kinetics of transdermal nicotine. Plasma concentrations of nicotine rose less rapidly, reached a lower peak, and peaked at a later time, indicating delayed absorption of transdermal nicotine after intravenous nicotine versus after transdermal nicotine administered alone. Nicotine is known to produce cutaneous vasoconstriction. The likely explanation for our observation is that intravenous nicotine constricts dermal blood vessels, thereby limiting percutaneous absorption. Other vasoconstrictor drugs would be expected to retard the absorption of transdermal nicotine and perhaps other transdermal drugs as well.     

局部麻醉透皮技术与整形美容手术

术中麻醉根据麻醉药物分布范围可分为全身麻醉和局部麻醉,其中局部麻醉在整形美容手术中的应用较为广泛。传统剂型经皮递送局麻药作用时间较短,且脂溶性差,限制了其在体表透皮方面的应用。近年来,随着麻醉技术的发展,新型体表镇痛局麻药递送系统可将涂抹于皮肤的药物递送至真皮层以阻滞神经末梢痛觉传入,从而达到镇痛的效果,提高了药物递送效率。此外,透皮给药相较于注射给药可显著增加给药安全性和患者舒适度。本文概述了常用的局麻药透皮吸收促进方法以及目前已上市的透皮局麻药物,并结合研究进展对局部麻醉透皮技术在整形美容手术中的应用和发展作一展望。     

Development of a novel transdermal system design

A new transdermal device design is presented in which the system is fabricated with the drug in an impermeable, pre-active state. The system is activated by the user immediately prior to application, thereby converting the impermeable drug into a permeable form. The new design can provide significant improvements in safety, stability and performance of transdermal drug delivery systems.