头孢氨苄缓释片的研制

目的:制备头孢氨苄缓释片,通过溶出度试验研究其生物利用度和药代动力学。方法:Eudragit Ⅱ和HPMC作为缓释材料制备头孢氨苄缓释片,并与日本进口头孢氨苄缓释片(Syncl SR tablets)进行了体外释放度比较。结果:本制备品与进口片溶出结果相似,经人体生物利用度研究表明,头孢氨苄缓释片比普通胶囊口服后能明显推迟达峰时间,并降低峰浓度(P<0.01),缓释片与普通胶囊的AUC_0→24之间没有显著性差异(P>0.05)。缓释片相对于普通胶囊生物利用度为(104.90±8.35)％。结论:体内和体外实验结果表明本品达到预期效果。     

头孢氨苄缓释胶囊的开发及人体生物利用度研究

通过制剂学手段延长头孢氨苄的释放,制成一日服2次代替原需分4次服用的口服制剂,以提高病人的顺应性和临床治疗效果。用微生物法测定头孢氨苄缓缓释胶囊在10例健康志愿者体内的药物动力学和生物利用度,并与进口复粒胶囊和普通胶囊进行了比较研究。生物利用度结果表明,缓释胶囊的有关药动学参数与进口复粒胶囊相比,均无显著性差异(P>0.05),与普通胶囊相比,T_(max)和T_(1/2)有显著的差异(P<0.05),而C_(max)和AUC均无显著性差异。缓释胶囊对进口复粒胶囊的相对生物利用度为98.70％,对普通胶囊为97.28％。     

头孢氨苄缓释片和普通胶囊的多剂量生物利用度和药物动力学比较

目的：比较头孢氨苄缓释片和普通胶囊的多剂量生物利用度和药物动力学。方法：１０例健康志愿者随机交叉口服ＣＥＸ缓释片５００ｍｇ，ｑ１２ｈ，ＣＥＸ普通胶囊２５０ｍｇ，ｑ６ｈ，服３ｄ达 后进行波动试验和稳态药物动力学研究，ＨＰＬＣ法测定血药浓度。结论：ＣＥＸ缓释片达峰时间延长，维持有效血药浓度的时间较长。     

克拉霉素缓释胶囊的制备与体外释放度研究

目的:制备克拉霉素缓释胶囊,考察不同包衣增质量对其体外释放特性的影响。方法:采用流化床包衣工艺,以3%羟丙基甲基纤维素为黏合剂,乙基纤维素水分散体(Surelease?)为缓释包衣材料,制备克拉霉素缓释胶囊。采用高效液相色谱法测定不同包衣增质量胶囊的体外释放度,并与进口缓释片的释放度进行比较。结果:成功制备克拉霉素缓释胶囊,包衣增质量为5%、8%、11%的自制缓释胶囊与进口缓释片比较,体外释放曲线相似因子f2分别为40.3、66.8、53.3。结论:该制剂制备工艺可行,包衣增质量为8%的克拉霉素缓释胶囊体外释放与进口缓释片基本一致。     

苦参素胃内滞留缓释片的研制及犬体内生物利用度研究

目的:制备苦参素胃内滞留缓释片,考察其体外释放度和体内血药浓度.方法:以羟丙甲基纤维素(HPMC)为骨架材料,十六醇作为助漂剂,碱式碳酸镁作为产气剂,制备了一天给药2次的苦参素缓释片,考察其在0.1 mol·L-1盐酸溶液中的释放度.建立HPLC法测定血浆中的药物浓度,采用BAPP2.0程序估算beagle犬服用市售苦参素普通胶囊(参比制剂)和受试制剂后的各个药动学参数,进行统计学分析,并采用Loo-Riegelman法考察体内外相关性.结果:所得胃内滞留缓释片体外释放度良好,在犬体内与市售胶囊相比有缓释效果,相对生物利用度为110.5%.结论:苦参素制成胃内滞留缓释片缓释效果明显,与受试制剂相比有显著差异,体内外相关性良好.     

头孢氨苄胃漂浮缓释片的制备与质量评价

目的制备头孢氨苄胃漂浮缓释片,并考察其漂浮延迟时间及体外药物释放度。方法采用粉末直接压片工艺制备头孢氨苄胃漂浮缓释片,采用单因素实验方法筛选得到影响头孢氨苄胃漂浮缓释片体外漂浮延迟时间、漂浮时间和释放度的关键性辅料用量范围,最终以羟丙甲纤维素(HPMC K15M)用量、碳酸氢钠用量以及压片主压力作为考察因素,以头孢氨苄胃漂浮缓释片的漂浮延迟时间和1,4和8 h时间点的药物释放度作为评价指标,通过Box-Behnken实验设计优化得到头孢氨苄胃漂浮缓释片处方设计空间,并在设计空间任取一点连续制备3批头孢氨苄胃漂浮缓释片,评价其漂浮延迟时间及体外释放度。结果优化得到头孢氨苄胃漂浮缓释片的处方设计空间,每片HPMC K15M用量为260 mg,碳酸氢钠用量为60 mg,压片主压力为8 kN,制备的头孢氨苄胃漂浮缓释片漂浮延迟时间仅为12.1±0.5 min,在12 h内药物释放平缓,无药物突释。结论通过Box-Behnken实验设计优化得到的头孢氨苄胃漂浮缓释片处方,漂浮延迟时间较短,12 h维持漂浮状态,药物释放平稳。     

褪黑素缓释片的制备及其药代动力学研究

目的　研制褪黑素HPMC骨架缓释片。并且研究缓释片的药物动力学及生物利用度。方法　以HPMC为骨架制备褪黑素缓释片。考察褪黑素的颗粒大小 ,片剂中HPMC的种类及含量 ,片剂大小 ,填充物的种类及数量 ,压片力等影响药物释放度的因素。采用HPLC荧光检测器测定家犬静脉注射及口服褪黑素后的血药浓度。结果　褪黑素静脉注射后体内血药浓度符合双隔室模型。静注两种剂量后AUC与剂量成正比 ,生物半衰期分别为 6 7 7分和 84 6分 (P >0 0 5 )。褪黑素缓释片相对于常释胶囊的生物利用度为 83 8%。缓释片及常释胶囊的绝对生物利用度分别为 3 75 %及 4 4 9%。结论　褪黑素缓释片具有良好的缓释特性。褪黑素缓释片及常释胶囊的绝对生物利用度都较低 ,缓释片的生物利用度低于常释胶囊但体内平均滞留时间显著长于常释胶囊。缓释片的体外释放与体内吸收速度有良好的相关性。     

亲水改性玉米朊提高硝苯地平生物利用度的研究

目的:利用亲水改性玉米朊为主要材料,以硝苯地平为模型药物,制备硝苯地平缓释片,提高难溶性药物的生物利用度。方法:测定自制硝苯地平缓释片的体内外释放行为,并与市售普通片比较研究硝苯地平缓释片的相对生物利用度,考察自制硝苯地平片的体内外相关性。结果:自制硝苯地平缓释片体外释放符合Higuchi方程,相对生物利用度为156.4%,体内外相关性良好。结论:亲水改性玉米朊可以明显提高难溶性药物的生物利用度。     

以羟丙基甲基纤维素为骨架的缓释片阻释剂研究

目的:研究不同的阻释剂对以羟丙基甲基纤维素(HPMC)为骨架制成的利巴韦林缓释片、头孢氨苄缓释片体外释放度的影响.方法:分别制粒、压片后,按照2000年版<中国药典>规定,进行体外释放度测定.结果:不同的阻释剂对利巴韦林缓释片、头孢氨苄缓释片体外释放度的影响不同.结论:作为阻释剂,乙基纤维素适用于头孢氨苄缓释片,硬脂酸适用于利巴韦林缓释片.     

阿莫西林漂浮缓释片的制备及体外释放度研究

目的　将阿莫西林制成胃漂浮缓释片 ,延长在胃中的停留时间 ,逐渐释放 ,提高生物利用度。方法　采用HPMC、十六醇等材料 ,全粉末直接压片法制备阿莫西林漂浮缓释片 ,并进行体外漂浮性与体外释放度的研究。结果　按L9(34)设计最佳制备工艺为A3 B1C2 ,阿莫西林漂浮缓释片具有很好的缓释效果。结论　制备漂浮缓释片是提高阿莫西林生物利用度的有效途径     

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.     

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.     

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.