评价固体制剂的体内外相关性的一种新方法

本文用隔室模型分别来描述药物在体外和体内的过程，并建立了药物在体内、外的动力学方程。通过求算方程中的体内、外港出速度参数Ｒ(ｉｎ)和Ｒ(ｏｕｔ)来评价药物的体内外相关性。采用模型药物盐酸曲马多的体内外数据，根据建立的动力学方程，用自编程序计算在０、２５、１００ｒｐｍ条件下的体外溶出参数Ｒ(ｏｕｔ)的值分别为９.０３±２．０３ｘ１０(－５)ｍＬ．ｍｇ(－２／３)ｍｉｎ(－１)，１.６３±０.９０ｘ１０(－４)ｍＬ·ｍｇ(－２／３)ｍｉｎ(－１)，１８０±０.６５ｘ１０(－４)ｍＬ·ｍｇ(－２／３)·ｍｉｎ(-1)，体内溶出参数Ｒ(ｉｎ)的值为６．２７±０.５２ｘ１０(－５)ｍＬ·ｍｇ(－２／３)·ｍｉｎ(－１)。结果表明，在上述三个不同转数的情况下，体外溶出参数Ｒ(ｏｕｔ)比体内溶出参数Ｒ(ｉｎ)稍大。据此，可以通过调整体外溶出条件进而能更精确地模拟体内溶出情况。     

喷雾干燥法制备阿司匹林肠溶微囊的实验研究

目的：采用喷雾干燥法制备阿司匹林肠溶微囊,建立质量评价方法。方法：采用丙烯酸树脂Ⅱ号为包衣材料,篦麻油为增塑剂,乙醇为溶剂,阿司匹林为囊心物,将囊材与囊心物按１：２和１：４的比例喷雾干燥制成微囊。结果：经扫描电镜和差示量热扫描法测定表明,微囊包裹形成。囊心物：囊材按１：４较好,微囊能迅速在人工肠液中释放,４５ｍｉｎ释药达到７５％,肠溶片４５ｍｉｎ释药低于６０％。结论：喷雾干燥法制备肠溶微囊,方法简     

常咯啉在实验性心律失常狗的药代动力学－药效动力学分析

用Ｈａｒｒｉｓ冠脉结扎法诱发的心律失常狗研究常咯啉药代动力学－药效动力学。７只狗按８３．３３μｇ·ｋｇ￣（－１）·ｍｉｎ￣（－１）静脉滴注６０ｍｉｎ，在给药期间和停药后不同时间记录ＥＣＧ及测定血药浓度。Ｃ－Ｔ数据用药代程序计算药代参数；药效数据用药代－药效同步分析模型计算药效动力学参数，Ｋ１０，Ｔ１／２，Ｖｄ，Ｃｌ分别为０．００８７ｍｉｎ￣（－１），７８．０３ｍｉｎ，４０．５５ｍｌ·ｋｇ￣（－１）和０．４２１ｍｌ·ｋｇ￣（－１）·ｍｉｎ￣（－１）；Ｋｅ０和Ｃｅ（５０）分别为０．００４８ｍｉｎ￣（－１）和２．０１μｇ·ｍｌ￣（－１）.     

多肽、蛋白质类药物微囊化的两种新型实用设备

介绍双喷嘴雾干燥和超声雾化－低温萃取两种多肽、蛋白质类药物微囊化的新型设备，分别举例阐明两者的工作原理。并根据药物微囊化的研究经验对上述设备的优点和实用性作了点评。     

奥昔非君膜剂的初步研究

研究了奥昔非君口腔药膜的处方和制备工艺。体外溶出试验表明本品在最初１～２ｍｉｎ内释药十分迅速，而全部药量在３～５ｍｉｎ内释放完毕。稳定性试验证明，本品性质稳定，经３７℃及长期室温贮存其溶出特征及含量均无明显变化。     

家兔静注水杨醛-N'-(2-呋喃硫羰基)腙铜配合物的药物动力学

目的：研究水杨醛－Ｎ′－（２－呋喃硫羰基）腙铜配合物（ＣＳＦＣ）在兔体内的药物动力学。方法：１０只家兔静脉注射ＣＳＦＣ５ｍｇ·ｋｇ－１，用反相ＨＰＬＣ法测定血清药物浓度。结果：ＣＳＦＣ的血药浓度－时间曲线符合二室开放模型，主要药动学参数为：Ｔ１２α＝３．４±１．７ｍｉｎ，Ｔ１２β＝６５．５±１４．６ｍｉｎ，Ｋ１２＝０．１１８３±０．０６６９ｍｉｎ－１，Ｋ２１＝０．０２２８±０．００６５ｍｉｎ－１，Ｋ１０＝０．１２０２±０．０４０７ｍｉｎ－１，Ｖ０＝０．３０５±０．１８４Ｌ·ｋｇ－１，ＣＬ＝１．８９６±０．４７０Ｌ·ｋｇ－１·ｈ－１，ＡＵＣ＝１７０．１±５７．０ｍｇ·ｍｉｎ－１·Ｌ－１。结论：ＣＳＦＣ在兔体内分布迅速而广泛，消除也较快。家兔静注５ｍｇ·ｋｇ－１，可维持抗结核杆菌有效血浓度６ｈ。     

超声雾化致过敏反应分析报告

１　病例资料　男，４０岁，半月前出现干咯，咽喉异物感，自服“复方草珊瑚含片”数日，症状无缓解，逐来我院耳鼻喉科求治，诊断为“咽喉炎”，做超声雾化治疗。用鞍山产ＪＷＣ－２Ｂ型超声波雾化器，给予庆大霉素针８万Ｕ，地塞米松针５ｍｇ，糜蛋白酶粉剂８０００Ｕ，用２０ｍｌ蒸馏水稀释放入药杯，超声频率１－７兆赫兹，雾粒直径０－５～１０微米，最大雾化量４～６ｍｌ／ｍｉｎ。将面罩对准口鼻，平静状态下做自然深呼吸，时间２０ｍｉｎ。开始治疗１０ｍｉｎ后，患者面潮红，无自觉症状，疑缺氧所致，休息后完成治疗。观察患者头…     

家兔静注依托泊甙的药物动力学研究

采用改良的ＨＰＬＣ法测定家兔血清中的依托泊甙，同时检测到两个代谢物，基本确定为顺依托泊甙和反依托泊甙羟基酸。家兔静注依托泊甙的药物动力学符合二室开放模型，其主要参数为：Ｔ１／２α＝３．００±１．９１ｍｉｎ，Ｔ１／２β＝５８．９３±４５．３５ｍｉｎ，Ｖｃ＝０．３８±０．２５Ｌ／ｋｇ，Ｃｌ＝０．０２±０．０１Ｌ·ｋｇ－１·ｍｉｎ－１，ＡＵＣ＝７４１．４０±３８２．６０μｇ·ｍｌ－１·ｍｉｎ－１。     

尼索地平光解稳定性研究

采用双波长分光光度系数倍率法测定尼索地平在不同浓度下在乙醇中的光解动力学参数。结果表明）当浓度低于３×１０－５ｍｏｌ·Ｌ－１时呈表观一级反应，速率常数为１．６２６×１０－２ｍｉｎ－１，而高于２×１０－４ｍｏｌ·Ｌ－１时则为零级反应，速率常数为１．２３８×１０－６ｍｏｌ·Ｌ－１·ｍｉｎ－１。此结果提示该药在生产、贮存及制剂学研究过程中，其浓度宜控制在２×１０－４ｍｏｌ·Ｌ－１以上。     

离子交换树脂再生条件的优化

采用均匀设计［１］考察离子树脂交换容量的最佳酸碱浓度、再生时间与淋洗速度，筛选结果阴阳离子交换树脂再生的优化条件为：阴树脂２ｍｏｌ·Ｌ－１氢氧化钠，再生时间０．５ｈ，淋洗流速为８０ｍｌ·ｍｉｎ－１，阳树脂２．７ｍｏｌ·－１Ｌ盐酸，再生时间３．５ｈ，淋洗流速为６０ｍｌ·ｍｉｎ－１。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.