国内口服脉冲给药制剂的研究进展

目的：了解近年来国内口服脉冲制剂的研究进展和基本情况。方法：根据包衣技术的不同比较了国内近几年来研制的主要几个脉冲制剂的处方设计、工艺特点、体内外研究实验结果等进行了综述，并提出了今后的研究方向。结果：国内投入研究的剂型均匀彩和膜包有技术的口服剂型，且研究不够全面深入，多数研究仅限于体外实验和动物实验。结论；国内外对于脉冲给药系统及其制剂的研究还有待于进一步加强。     

口服缓控释系统的研究进展

目的:综述口服缓控释系统的研究进展。方法:以"骨架片""渗透泵片""纳米技术""缓控释制剂"等为关键词,在Elsevier期刊、清华大学镜像、中国期刊全文数据库等检索源检索相关文献,筛选2009-2014年口服缓控释系统的释药机制、剂型及制备技术等研究进行综述。结果:共检索到相关文献651 055篇,其中有效文献237篇。口服缓控释制剂的释药机制主要有扩散、溶蚀、溶出、渗透泵和离子交换等,常用剂型有骨架片、渗透泵片、胃滞留制剂、结肠定位制剂、定时脉冲胶囊等,最新的制备技术有纳米制剂技术、靶向制剂技术、固体分散技术和半固体制剂技术等。结论:口服缓控释系统的研究与开发已经成为缓控释制剂发展的一个重要方向,但作为一种新型给药系统仍需进一步研究。     

口服脉冲控释给药系统的释药机制及其应用

口服脉冲控释给药系统因具有定时或定位释放的特点而成为当前药剂研究领域的热点.本文介绍了其释药机制,包括有机酸诱导、渗透压调节、pH依赖、时间依赖、酶依赖、pH-时间依赖及各释药机制应用实例.提出了该给药系统在应用中,尤其是对中药复方制剂所存在的一些问题,期望为口服中药脉冲控释给药系统的研究提供思路.     

脉冲释药系统及相关制剂研究进展

目的:介绍脉冲释药系统及相关制剂的研究进展。方法:整理近年来的相关文献,对脉冲释药系统的特点和类型以及各种脉冲释药制剂的研究情况进行综述。结果:脉冲释药系统的特点包括可按需定时定量释药、预防疾病发作和减少不良反应、降低产生耐药几率、避免肝脏首关效应、增加患者依从性等。脉冲释药系统的类型包括本体溶蚀系统、表面溶蚀系统、酶降解激活释药系统、渗透压激发释药系统、超声波激发释药系统等。脉冲释药制剂涵盖了口服(如包衣片剂、胶囊剂、微丸)、注射(如注射微球制剂)、外用(如透皮贴剂)等各个领域。结论:随着研究水平的提高,借助于新辅料和制剂新技术,更多的药物将被制成脉冲释药制剂,脉冲释药系统会有更大的发展。     

熔融沉积成型3D打印法莫替丁口服脉冲制剂的研究（英文）

为了制备具有不同药物延迟释放时间,按照患者需求实现个性化给药的脉冲制剂,本研究将熔融沉积成型(fuseddepositionmodeling,FDM)3D打印技术引入制剂领域,探讨了以该技术结合传统工艺制备核壳型口服脉冲制剂的可行性。该制剂的“核”是以传统工艺制备的市售片剂,而不含药物的外层壳是以FDM 3D打印技术制备的。本研究采用不同参数设计了三种外壳的片剂,并对其形态、尺寸、片重、硬度和体外释药进行了表征和评价。结果表明3D打印片剂外型完好,无缺陷。脉冲片剂的大小、片重、硬度及体外释药行为均与外壳参数相关,通过调节外壳参数可以实现药物个性化的体外5–7小时的延迟释放。本研究探索了制备脉冲制剂的新方法和实现脉冲制剂个性化给药的新途径。     

中药口服缓控释制剂的研究进展

目的：通过对中药口服缓控释制剂进行综合论述,为我国中药缓控释制剂的研究与发展提供参考经验。方法：全面收集掌握近十年以来世界范围内中药口服缓控释制剂的研究资料与结果,从中药缓控释制剂的类型、体内释放评价、体外释放评价以及体内外相关性等方面进行研究。结论：目前,世界范围内的中药口服缓控释制剂的研究主要侧重点在于制剂加工生产工艺和体外释药性等方面,中药口服缓控释制剂的生物利用度、体内释药特性和药动学过程等生物药剂学方面的研究涉及比较少,中药口服缓控释制剂的设计原理和质量评价体系方面的研究基本上还没有起步。因此,需要全面扩充中药口服缓控释制剂的研究内容,加大研究力度,持续拓展研究空间,以提升我国中药口服缓控释制剂的研究与发展水平。     

盐酸维拉帕米脉冲释放片家犬体内的药动学及生物利用度

目的：比较盐酸维拉帕米脉冲释放片与其片芯在家犬体内的药动学特征及生物利用度。方法：采用拉丁方设计,将家犬6只随机分为2组,交叉口服Ⅳ型脉冲片和片芯,以片芯为对照制剂,考察体内脉冲效果。结果：Ⅳ型脉冲片在家犬体内的时滞为4h,而Cmax、AUC等无明显差异,达到设计要求。结论：本研究制备的脉冲释放制剂为防治心血管疾病的凌晨发作提供了一个良好的剂型选择。     

卡马西平制剂的研究进展

通过查阅大量的文献,对近年来卡马西平在制剂方面的研究进展进行整理分析,阐述卡马西平制剂在各种给药途径特别是口服给药的新进展,提出今后的研究方向重点是提高卡马西平口服制剂的生物利用度和改善口服制剂的稳定性。     

药用高分子在缓控释制剂中的应用现状

<正>缓控释制剂的发展除与制药设备的不断发展、革新有关外,药用高分子在该类制剂中也是不可分割的重要组成部分。近年来,一些新型高分子材料的研究和应用使缓控释制剂步入了定时、定向、定位、速效、高效、长效的精密化给药阶段,出现了口服渗透泵控释制剂、脉冲式释药系统、环境敏感型定位释药系统、结肠定位给药系统等新型缓控释制剂。辅料的成分、组成与结构对药物的释放性能有很大的影响,因此在缓控释制剂中合理应用新型高分子材料,就具有重要的意义。1药用高分子作为药物载体药用高分子的广泛研究和应用,促进了缓控释制剂的快     

脉冲给药系统研究进展

脉冲给药系统是随着时辰生物学和时辰药理学研究的不断深入而发展起来的,是以制剂手段控制药物释放时间及给药剂量来配合生理节律的变化,从而保证疗效,减轻不良反应,临床应用前景良好。为此,本文综述国内外的相关文献,简要介绍了脉冲给药系统的释药机理,并讨论了近年来脉冲给药系统在临床上的应用情况,提出了中药复方脉冲制剂在研究中所存在的一些问题,期望为中药脉冲给药系统的研究提供思路。     

Ophthalmic drug delivery systems

New ophthalmic drug delivery systems are curently receiving increased attention, in part because of the expected emergence of new drugs with short biological half-lives whose usefulness may depend on a more continuous drug supply than eyedrops can provide, but also because of the potential of some delivery systems to reduce the side effects of the more potent drugs recently introduced or presently under investigation. Some ophthalmic delivery systems extend the duration of drug action by enhancement of corneal absorption; these systems include soluble gels and emulsions, hydrophilic ocular inserts, ion-pair associations, prodrugs, and liposomes. Since these systems enhance the “pulse entry” of the drug, they are limited to use with drugs whose dose-related side effects are not serious. Other delivery systems provide for a controlled release of drugs and therefore minimize the pulse entry with which side effects are associated. They can be based on any of several different mechanisms and include both erodible and nonerodible matrices. The various delivery systems that have recently been developed and those that are currently known to be under investigation are described in this paper, along with some observations regarding the future outlook of ophthalmic drug delivery systems.     

Transdermal Delivery of Metoprolol by Electroporation

Electroporation, i.e., the creation of transient pores in lipid membranes leading to increased permeability, could be used to promote transdermal drug delivery. We have evaluated metoprolol permeation through full thickness hairless rat skin in vitro following electroporation with an exponentially decaying pulse. Application of electric pulses increased metoprolol permeation as compared to diffusion through untreated skin. Raising the number of twin pulses (300 V, 3 ms; followed after 1 s by 100 V, 620 ms) from 1 to 20 increased drug transport. Single pulse (100 V, 620 ms) was as effective as twin pulse application (2200 V, 1100 V or 300 V, 3 ms; followed after 1 s by 100 V, 620 ms). In order to investigate the effect of pulse voltage on metoprolol permeation, 5 single pulses (each separated by 1 min) were applied at varying voltages from 24 to 450 V (pulse time 620 ms). A linear correlation between pulse voltage and cumulative metoprolol transported after 4 h suggested that voltage controls the quantity of drug delivered. Then, the effect of pulse time on metoprolol permeation was studied by varying pulse duration of 5 single 100 V pulses from 80 to 710 ms (each pulse also separated by 1 min). Cumulative metoprolol transported after 4 h increased linearly with the pulse time. Therefore, pulse time was also a control factor of the quantity of drug delivered but to a lesser extent than the voltage at least at 100 V. The mechanisms behind improved transdermal drug delivery by electroporation involved reversible increased skin permeability, electrophoretic movement of drug into the skin during pulse application, and drug release from the skin reservoir formed by electroporation. Thus, electroporation did occur as shown by the increased transdermal permeation, on indicator of structural skin changes and their reversibility. Electroporation has potential for enhancing transdermal drug delivery.     

Bepridil block of recombinant human cardiac IKs current shows a time-dependent unblock

Whole-cell patch-clamp techniques were employed to examine the effects of bepridil, a Ca2+ channel blocker with Vaughan Williams class III action, on a slow component of cardiac delayed rectifier K+ current (IKs), which was reconstituted in HEK293 cells by transfecting KCNQ1 and KCNE1. Micromolar bepridil inhibited tail currents carried by KCNQ1/KCNE1 channels in a concentration-dependent manner (IC50 = 5.3 +/- 0.7 microM at -40 mV from 1000 milliseconds test pulse). When the effect of the drug was examined with a short test pulse protocol (250 milliseconds), IC50 became two-fold smaller than that measured with 1000 milliseconds test pulse (2.5 +/- 0.8 microM). The envelope-of-tails protocol was used to assess how the duration of depolarizing pulse affects the drug action on the outward KCNQ1/KCNE1 channel current. The drug significantly inhibited tail currents more potently during shorter pulses (<600 milliseconds). Bepridil's block was therefore time dependent, and its binding affinity to the channel was greater in the closed state channel, as evidenced by unblocking during prolonged depolarization. These properties of channel blockade appear to underscore the mechanism of bepridil's effect on IKs current.     

Actions of a mixture of amphetamine and a barbiturate in man

The effects in man of a mixture of amphetamine and a barbiturate (15 mg of amphetamine sulphate and 300 mg of cyclobarbitone) and of each of the constituents separately were assessed on the performance of simple mental and motor tasks, on the pulse rate and on subjective reports. The mixture produced a pattern of effects which was different from that produced by either drug separately. It impaired the efficiency of the performance of tasks much less than did the barbiturate drug alone; it produced almost as big a rise in the pulse rate as did amphetamine alone; and it produced reports of feeling “elated” from many more subjects than did either drug separately, though there was no corresponding increase in reports of other feelings and sensations.     

脉冲给药系统的研究进展

脉冲给药系统是根据时辰药理学与时辰治疗学特点研究而设计的一种新型迟释给药制剂。文章查阅了近几年国内外相关文献,阐述了脉冲给药系统的释药机制,包括生物化学刺激(胃肠道酸碱度、酶敏感度、葡萄糖敏感度等),物理化学刺激(声波、磁场、电场、温度等),膨胀爆破释药机制以及定时脉冲塞胶囊释药机制,并总结了基于各类释药机制的脉冲释药系统在药剂学中的应用研究进展。     

用电致孔法促进环孢素A的皮肤滞留

目的研究致孔电压、致孔时间及脉冲模式对环孢素A在大鼠皮肤各层中滞留的影响。方法将质量分数为0.5%的环孢素A的乙醇(体积分数为40%)混悬液应用于离体大鼠皮肤,同时在大鼠皮肤施加电致孔。实验结束后,用胶带剥离法分离角质层,HPLC法测定角质层和大鼠去角质层皮肤及接受液中的药物含量。结果大鼠表皮和真皮中环孢素A的含量随致孔电压的升高略有增加,随致孔时间的增加而增加,使用3次/min的脉冲模式大鼠去角质层中的药物滞留量最多,并且使用电致孔这一物理促渗法未显著增加接受液中环孢素A的含量。结论电致孔法能够提高环孢素A皮肤局部用药效果,从而减少药物体循环带来的不良反应。     

参仙升脉口服液治疗低血压伴心动过缓的临床研究

目的观察参仙升脉口服液治疗缓慢性心律失常伴低血压临床疗效观察及药物不良反应。方法缓慢性心律失常伴低血压患者58例,均根据病情给予参仙升脉口服液治疗,观察治疗前后患者心率变化及药物不良反应。结果参仙升脉口服液治疗缓慢性心律失常伴低血压1个疗程后,显效患者21例,显效率为36.21%（21/58）,有效患者32例,有效率为55.17%（32/58）,治疗1个疗程患者总有效率为91.38%（53/58）。结论参仙升脉口服液在治疗缓慢性心律失常伴低血压方面,临床疗效显著,无明显的不良反应,在临床工作中可精选适应证,密切观察患者的不良反应,谨慎地推广使用。     

Transdermal drug delivery using electroporation. II. Factors influencing skin reversibility in electroporative delivery of terazosin hydrochloride in hairless rats

A previous study indicated that the parameters governing the performance of electroporative delivery to the skin, are voltage, pulse length, number of pulses and electrode area.1 This article describes a study in which the reversibility of the electroporation technique is evaluated with in vitro methods. The skin's reversal from an enhanced permeation mode as a result of electroporation to the base level was used as an index to understand the mechanism of drug delivery and also as a preliminary indicator of safety. Maximum delivery of the model drug, terazosin hydrochloride, occurred during the pulsing. Electroporative delivery with a wire electrode (small-area electrode, 0.56 cm(2)) using 20 pulses at U(skin,0) 88 V, and pulse length 20 ms, did not cause any damage to the skin. Increasing the pulse length to 60 ms, while keeping the rest of the parameters fixed, caused a visible change in the external appearance of the skin. However, with the use of a spiral electrode (large-area electrode, 2.74 cm(2)) at 60-ms pulse length, there was minimal damage to the skin. This may be attributed to the more uniform flow of current over the whole skin area. The large-area electrode required a smaller electrode voltage, U(electrode,0) for any given U(skin,0) and also delivered nearly double the instantaneous power density compared with the small-area electrode. These findings indicate that using shorter pulses and large-area electrodes is a safer technique than large pulses and small-area electrodes when electroporation is used to enhance skin's permeability for drug delivery.     

老年高血压400例临床分析

目的探讨本地区老年人高血压的临床特点。方法回顾性分析400例60岁以上高血压患者的临床资料。结果单纯性收缩期高血压120例（30％），脉压差〉60mmHg者200例（50％），合并心脑肾损害者320例（80％），合并糖尿病者200例（50％），不同程度心理障碍者180例（45％）。单用一种降压药能控制60例（15％），联合二种以上降压药340例（85％）。因降压过快而发生意外事件40例（10％），死于心脑危象80例（20％）。结论老年单纯性收缩期高血压所占比例较大，脉压差大、并发症多且严重。合理用药、缓慢降压是治疗老年高血压的关键。     

右佐匹克隆定时释放片的制备研究

目的制备右佐匹克隆定时释放片,并考察其体外释药特性。方法分别以HPMC作为溶胀层包衣材料,以乙基纤维素水分散体作为控释层包衣材料,采用高效包衣机制备右佐匹克隆定时释放片,考察影响释放度的主要因素,并测定体外释放度以考察体外释药行为。结果确定了影响右佐匹克隆释放的处方因素,体外释放度研究结果表明,该制剂可达到脉冲式释放。结论右佐匹克隆定时释放片可以达成两次定时脉冲释放,符合让失眠患者快速入睡并维持6 h以上睡眠状态的设计初衷。