多肽透皮给药研究进展

针对近年来多种多肽类药物的透皮给药系统进行综述。通过查阅国内外多种相关期刊文献。将多肽类药物透皮给药方法分为化学促渗剂、多种物理促渗技术,以及透皮肽、微针技术并对其进行论述。反向离子导入技术应用前景广阔,微针给药系统研究逐步深入,出现了胰岛素智能化微针给药系统,透皮肽的研究发展迅速,相信未来多种蛋白质及多肽的透皮给药方式将应用于临床,极大地促进医疗事业的发展。     

促进多肽和蛋白质类药物透皮给药技术的研究进展

综述了近年来以物理方法促进多肽和蛋白质药物透皮给药技术研究的进展,包括目前广泛研究的离子导入、电致孔导入和超声导入技术。     

促进多肽和蛋白质类药物透皮给药技术的研究进展

综述了近年来以物理方法促进多肽和蛋白质药物透皮给药技术研究的进展,包括目前广泛研究的离子导入、电致孔导入和超声导入技术.     

促进多肽和蛋白质类药物透皮给药技术的研究进展

综述了近年来以物理方法促进多肽和蛋白质药物透皮给药技术研究的进展，包括目前广泛研究的离子导入、电致孔导入和超声导入技术。     

渗透促进剂对胰岛素体外经皮离子导入渗透性的影响

本文考察了某些渗透促进剂如月桂氮Zhuo酮（AZ）、油酸（OA）、泊洛沙姆（POL）和丙二醇（PG）等对胰岛素体外经皮离子导入渗透性的影响。结果表明AZ对离子导入具有协同作用，PG能够增强这种作用，三者并用对胰岛素的经皮渗透具有特别显著的促渗效果。5％AZ／PG与离子导入并用后，较单独离子导入处理组的促渗因子为2.75。OA不能增强离子导入的作用，离子导入与某些渗透促进剂并用为胰岛素等大分子多肽类药物的透皮给药提供了新的思路和可能。     

离子导入经皮给药系统

综述了离子导入技术的基本组成、促渗机制、影响因素及应用前景。离子导入技术可有效提高药物的经皮渗透性，该技术扩大了经皮给药系统的研究范围，其对多肽和蛋白质等大分子药物的透皮促渗作用日益受到关注。     

制剂新技术在多肽、蛋白质类药物给药系统研究中的应用

目的　介绍制剂新技术在多肽、蛋白质类药物给药系统研究中的应用。方法　综述了多肽、蛋白质类药物的性质特点和影响其稳定性的原因;制剂新技术在多肽、蛋白质类药物给药系统中的运用;对LHRH及其类似物和胰岛素两类药物的新型制剂研究进行了概述。结果　脂质体、微乳和复乳、微球、纳米粒、自控式释药技术等制剂新技术广泛应用于多肽、蛋白质类药物给药系统中,取得了较大进展;黄体激素释放激素(LHRH)及其类似物和胰岛素两类药物的新剂型研究具有代表性且引人注目。结论　将制剂新技术用于多肽、蛋白质类药物给药系统的研究,有着广阔的应用前景     

制剂新技术在多肽、蛋白质类药物给药系统研究中的应用

目的 介绍制剂新技术在多肽、蛋白质类药物给药系统研究中的应用。方法 综述了多肽、蛋白质类药物的性质特点和影响其稳定性的原因;制剂新技术在多肽、蛋白质类药物给药系统中的运用;对LHRH及其类似物和胰岛素两类药物的新型制剂研究进行了概述。结果 脂质体、微乳和复乳、微球、纳米粒、自控式释药技术等制剂新技术广泛应用于多肽、蛋白质类药物给药系统中,取得了较大进展;黄体激素释放激素(LHRH)及其类似物和胰岛素两类药物的新剂型研究具有代表性且引人注目。结论 将制剂新技术用于多肽、蛋白质类药物给药系统的研究,有着广阔的应用前景。     

药物经皮离子导入的转运机制

药物经皮离子导入的转运机制郝劲松，郑俊民沈阳药科大学药学系１１００１５刑颖双鸭山矿务局总医院１５５１００随着生物工程技术的发展，已有些蛋白质多肽类药物应用于临床．由于这类药物口服时易受胃肠道酶降解和肝脏首过作用的影响，且稳定性差，生物半衰期短，高亲水...     

蛋白质和多肽类药物口服给药研究进展

蛋白质和多肽类药物具有良好的选择性和生物活性,已成为治疗众多疾病的首选药物。由于胃肠道内酶的降解作用以及肠道粘膜的低通透性,蛋白质和多肽类药物口服生物利用度极低,其常规给药一直以注射为主。为了使蛋白质和多肽类药物能够广泛应用于临床,研究人员对蛋白质和多肽类药物口服给药系统做了大量研究。目前用于提高蛋白质和多肽类药物口服生物利用度的方法主要有微粒给药系统、内源性细胞转运系统、应用酶抑制剂和黏附给药系统等。文章就这些方法在蛋白质和多肽类药物口服给药中的应用进行了综述。     

Transdermal lontophoretic Delivery of Luteinizing Hormone Releasing Hormone (LHRH): Effect of Repeated Administration

The transdermal iontophoretic delivery of the reproductive peptide hormone, luteinizing hormone releasing hormone (LHRH) is investigated in the isolated perfused porcine skin flap model (IPPSF). LHRH is delivered twice in a single flap experiment in efforts to identify factors inherent to iontophoretic delivery that might effect the drug flux of a subsequent iontophoretic episode. Initial iontophoretic delivery of LHRH is quite reproducible; however, subsequent iontophoretic episodes result in widely divergent fluxes thought to be caused by iontophoretic influences on the skin. Iontophoretic application of a drug on a previous active site, enhances the flux during the second application. A mass balance study is performed to explain these findings. By iontophoretically delivering I¹²⁵ labelled LHRH in the isolated perfused porcine skin flap model, the entire iontophoretic dose is identified and quantified. A drug depot is identified in the skin underlying the electrode which is approximately two times as large as the entire mass of drug delivered systemically.     

Stability of peptides during iontophoretic transdermal delivery

Degradation of thyrotropin releasing hormone (TRH) and insulin was investigated during iontophoretic transdermal delivery in vitro in varied buffer solutions and under various experimental conditions. A large current density enhanced deterioration of TRH during transdermal iontophoresis. Skin or external electrical potential increased the rate of deterioration, as did elevated temperatures. Peptide transformations took place and were significantly influenced by the physiological and pathological status of the skin and the electrochemical conditions during iontophoresis. Skin metabolism and electrical deterioration during iontophoretic transdermal transport was significant, especially at elevated temperature. Decreased temperature or added agents decreased the rate of degradation.     

Transdermal iontophoresis

Iontophoresis is a technique used to enhance the transdermal delivery of compounds through the skin via the application of a small electric current. By the process of electromigration and electro-osmosis, iontophoresis increases the permeation of charged and neutral compounds, and offers the option for programmed drug delivery. Interest in this field of research has led to the successful delivery of both low (lidocaine) and high molecular drugs, such as peptides (e.g., luteinising hormone releasing hormone, nafarelin and insulin). Combinations of iontophoresis with chemical enhancers, electroporation and sonophoresis have been tested in order to further increase transdermal drug permeation and decrease possible side effects. In addition, rapid progress in the fields of microelectronics, nanotechnology and miniaturisation of devices is leading the way to more sophisticated iontophoretic devices, allowing improved designs with better control of drug delivery. Recent successful designing of the fentanyl E-TRANS iontophoretic system have provided encouraging results. This review will discuss basic concepts, principles and applications of this delivery technique.     

Passive and iontophoretic controlled delivery of salmon calcitonin through artificial membranes

The development of a transdermal delivery system for drug molecules of high molecular weight (peptides or proteins) is nowadays a great scientific and commercial challenge. For these molecules, the passive transport through the skin is generally very low and should be enhanced by the application of the electrical current (a method called iontophoresis). A very important component of a transdermal iontophoretic system is the artificial membrane, which acts as the interface between the drug reservoir and the skin. The optimum membrane should (i) provide an effective drug delivery; (ii) have low electrical resistance and (ii) have low drug adsorption. In this work, the selection of membrane(s) for a transdermal iontophoretic salmon calcitonin (sCT, MW approximately 3500) system is performed. The passive and iontophoretic transport of sCT through porous artificial membranes, the sCT adsorption to them and the electrical resistance of all porous membranes in iontophoretic experiments is studied. The sCT transport through the membranes is compared with that through human skin, and based on the above three criteria the optimum membranes are selected for the sCT transdermal system.     

Investigation of the carbopol gel of solid lipid nanoparticles for the transdermal iontophoretic delivery of triamcinolone acetonide acetate

The purpose of this study was to investigate solid lipid nanoparticles (SLN) hydrogel for transdermal iontophoretic drug delivery. Triamcinolone acetonide acetate (TAA), a glucocorticoids compound, was employed as the model drug. SLN containing the drug triamcinolone acetonide acetate (TAA-SLN) and their carbopol gel with stable physicochemical properties were prepared. The use of TAA-SLN carbopol gel as a vehicle for the transdermal iontophoretic delivery of TAA was evaluated in vitro using horizontal diffusion cells fitted with porcine ear skin. We found that the TAA-SLN gel possessed good stability, rheological properties, and high electric conductance. Transdermal penetration of TAA from TAA-SLN gel cross the skin tissue was significantly enhanced by iontophoresis. The enhancement of the cumulative penetration amount and the steady-state penetration flux of the penetrated drug were related to the particle size of TAA-SLN and the characteristics of the applied pulse electric current, such as density, frequency, and on/off interval ratio. These results indicated that SLN carbopol gel could be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.     

Passive and iontophoretic transdermal delivery of phenobarbital: Implications in paediatric therapy

The objective of this investigation was to evaluate phenobarbital transdermal delivery for possible use in paediatric care. In vitro experiments were performed using intact pig skin and barriers from which the stratum corneum had been stripped to different extents to model the less resistant skin of premature babies. Cathodal iontophoretic delivery of phenobarbital was superior to anodal transport and optimised delivery conditions were achieved by reduction of competing co-ion presence in the drug formulation. Phenobarbital transport across intact or partially compromised skin was controlled by iontophoresis which was more efficient than passive diffusion. Across highly compromised skin, however, passive diffusion increased drastically and iontophoretic control was lost. Overall, this study demonstrates the feasibility of phenobarbital transdermal delivery for paediatric patients.     

布洛芬离子导入溶液剂的生物利用度

目的：观察布洛芬离子导入溶液剂在家兔体内的药物动力学和生物等效性。方法：布洛芬离子导入溶液剂经皮离子电导给药采用反相高效液相色谱法测定血药浓度，计算药物动力学参数并进行生物等效性评价。结果：布洛芬离子导入给药法的吸收速度快于透皮给药组，且ＡＵＣ及Ｃｍａｘ分别为透皮给药组的３．７倍和５倍。结论：布洛芬离子导入溶液剂经皮给药系统可代替传统的口服方式。     

Transdermal delivery systems

Based on a number of revolutionary ideas in the early seventies the development of transdermal delivery systems (TDS) for systemic therapy has been receiving considerable attention, both in academia and in the pharmaceutical industry. About ten years after a number of products were successfully put on the market, it has become clear that transdermal delivery of drugs not only exhibits appealing therapeutic prospects but may also provide a viable economic basis for future activities of the pharmaceutical industry. The paper will briefly stress some of the fundamentals of transdermal delivery with respect to the skin as absorption site. The main focus will be on transdermal delivery systems, covering design of transdermal systems, manufacturing of transdermal systems, polymers and adhesives, in vitro and in vivo testing of transdermal systems, principles of delivery control, and modelling of transdermal delivery. The final section will describe the fundamental strategies for enhancing drug permeation through the skin by alteration of barrier properties, approaches for thermodynamic activity increase of drug, and the iontophoretic transdermal delivery of drugs.     

Iontophoretic drug delivery

The composition and architecture of the stratum corneum render it a formidable barrier to the topical and transdermal administration of therapeutic agents. The physicochemical constraints severely limit the number of molecules that can be considered as realistic candidates for transdermal delivery. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. The principal distinguishing feature is the control afforded by iontophoresis and the ability to individualize therapies. This may become significant as the impact of interindividual variations in protein expression and the effect on drug metabolism and drug efficacy is better understood. In this review we describe the underlying mechanisms that drive iontophoresis and we discuss the impact of key experimental parameters-namely, drug concentration, applied current and pH-on iontophoretic delivery efficiency. We present a comprehensive and critical review of the different therapeutic classes and molecules that have been investigated as potential candidates for iontophoretic delivery. The iontophoretic delivery of peptides and proteins is also discussed. In the final section, we describe the development of the first pre-filled, pre-programmed iontophoretic device, which is scheduled to be commercialized during the course of 2004.