替硝唑凝胶的研制

目的：研制替硝唑凝胶。方法：用卡波姆９４０ 作凝胶基质制备替硝唑凝胶,建立了酸碱度、卫生学、含量测定等质量控制标准,对制剂进行了刺激性试验,离心试验,留样观察,光照试验。结果：ｐ Ｈ 值４ ．５ ～７ ．０ ,卫生学检查符合规定,含量测定平均回收率为１００ ．２６ ％ , Ｒ Ｓ Ｄ 为０ ．８７ ％ （ ｎ ＝ ６） ,且凝胶稳定无变化,无刺激性。结论：本方法设计合理,稳定性好,可满足临床需要。     

复方酮康唑凝胶剂的研制方法研究

目的制备复方酮康唑凝胶并建立其质控方法。方法以卡波姆-940为凝胶基质,建立酸碱度、卫生学、含量测定等质控方法,并进行刺激性试验、高速离心试验、耐热耐寒试验和室温留样观察等。用高效液相色谱法,C18柱,甲醇-水(75∶25)为流动相,检测波长为240nm,流速1.0ml/min测定复方酮康唑凝胶中酮康唑的含量。结果该剂pH为6.5～7.0,卫生学检查符合规定,酮康唑在4.0～16.0μg/ml范围内,峰面积与浓度呈良好的线性关系(r=0.9999),平均回收率为99.51%,日内相对标准偏差(RSD)为0.86%,日间RSD为1.02%。结论复方酮康唑凝胶剂制备工艺简单,所得制剂质量可控,性质稳定,无刺激性,临床疗效可靠,可满足临床需要。     

复方阿昔洛韦眼用凝股的利备及临床应用

目的制备复方阿昔洛韦眼用凝胶,提供治疗单纯疱疹性角膜炎的药剂.方法制备并测定制剂中阿昔洛韦含量,进行体外试验、稳定性试验.结果制剂制备方法合理,测定阿昔洛韦含量,可排除凝胶基质的干扰;稳定性试验和体外释放试验表明本制剂质量稳定并有缓释作用;通过60例单纯疱疹性角膜炎病人的临床应用,总有效率为96.7%.结论制剂质量稳定,对眼部无刺激,且持药时间长,是临床治疗单纯疱疹性膜炎的较理想制剂.     

阿奇霉素凝胶的制备及质量控制

目的：建立阿奇霉素凝胶的制备及质量控制方法。方法：用卡波姆－940作凝胶基质制备阿奇霉素凝胶。进行了酸碱度及卫生学、稳定性、透皮吸收、皮肤刺激性等试验及含量测定。结果：pH值6．5－7．5,卫生学检查符合规定，凝胶稳定无变化无刺激性，含量测定平均回收率为100．7％。结论：本方法设计合理，稳定性好，可满足临床需要。     

阿昔洛韦凝胶剂的制备及质量控制

目的 制备阿昔洛韦凝拉剂。方法 以卡波普水凝胶为基质制备阿昔洛韦凝胶剂,采用紫外分光光度法进行含量测定,并进行稳定性和皮肤刺激性试验。结果 阿昔洛韦在２５２ｎｍ有最大吸收峰,在４～１６ｕｇ／ｍｌ浓度与吸收度线性关系良好。线性回归方程为Ｃ＝１７．７９１８Ａ＋０．２０７２,ｒ＝０．９９９６,平均回疏率（ｎ＝５）为９９．７２％,ＲＳＤ＝０．４２％。结论 阿昔洛韦凝胶剂性质稳定,皮肤刺激性小,制备简单,易     

复方水杨酸凝胶的研制及质量控制

目的:制备复方水杨酸凝胶,并建立质量控制方法.方法:采用正交试验法筛选最佳基质处方,以三乙醇胺为中和剂,加入水杨酸和苯甲酸制成凝胶剂;建立酸碱度、卫生学、含量测定等质控方法,进行刺激性试验,离心试验,耐热耐寒试验.结果:pH 6.0～7.0,其他各项检查均符合凝胶剂的有关规定,水杨酸和苯甲酸的平均回收率分别为99.4%,98.1%,RSD分别为0.52%(n=6),0.63%(n=6).结论:本制剂制备工艺简单,性质稳定,质量可控,适于医院制剂.     

阿西美辛脂质体凝胶剂的研制

目的研制阿西美辛脂质体凝胶剂,并进行评价.方法采用不同方法、不同药-脂比处方制备脂质体,然后对其包封率进行比较,从而优选出最佳制备方法与最佳处方,并进一步制备成脂质体凝胶剂;采用HPLC测定制剂中阿西美辛的含量,葡聚糖凝胶柱结合HPLC测定制剂中阿西美辛的包封率;考察了制剂的皮肤刺激性与初步稳定性.结果制剂的含量控制在0.09%～0.110%范围之内;平均包封率为(58.76±12.47)%;无皮肤刺激性;不易高温贮存,对光不稳定.结论经初步评价,所制备的阿西美辛脂质体制备方法可行、简便、质量稳定.     

阿昔洛韦羟丙基-β-环糊精包合物滴眼液的制备及质量控制

目的:建立阿昔洛韦羟丙基-β-环糊精包合物滴眼液的制备工艺及质量控制方法。方法:采用饱和水溶液法制备阿昔洛韦羟丙基-β-环糊精包合物滴眼液,高效液相色谱法测定制剂中阿昔洛韦的含量,考察制剂稳定性及对兔眼刺激性。结果:阿昔洛韦标准曲线在5～40mg.L-1之间有较好的线性关系(r=0.9997),含量测定平均回收率为(100.36±1.17)%,日内、日间RSD分别小于1.23%,1.19%;制剂稳定性良好,对家兔眼无刺激性。结论:本制备工艺简单,质控方法可靠,可满足眼科临床用药需要。     

复方酮康唑凝胶剂的制备与质量控制

［摘要］目的制备复方酮康唑凝胶并建立其质量控制方法。方法以卡波姆 940为凝胶基质，建立酸碱度、卫生学、含量测定等质量控制方法，并进行刺激性实验、高速离心实验、耐热耐寒实验和室温留样观察等。用高效液相色谱（HPLC）法，C18柱，甲醇 水（75：25）为流动相，检测波长为240 nm，流速1.0 mL·min 1测定复方酮康唑凝胶中酮康唑的含量。结果复方酮康唑溶液pH值为6.5～7.0，卫生学检查符合规定，酮康唑浓度在4.0～16.0 μg·mL 1范围内，蜂面积与浓度呈良好的线性关系（r=0.999 9），平均回收率为99.52%，RSD为0.74%。日内RSD为 0.86%，日间RSD为1.02%。结论该品种制备工艺简单，所得制剂质量可控，性质稳定，无刺激性，可满足临床需要。     

复方阿昔洛韦眼用凝胶的制备及临床应用

目的：制备复方阿昔洛韦眼用凝胶,提供治疗单纯疱疹性角膜炎的药剂。方法：制备并测定制剂中阿昔洛韦含量,进行体外试验,稳定性试验。结果：制剂制备方法合理,测定阿昔洛韦含量,可排除凝胶基质的干扰;稳定性试验和体外释放试验表明本制剂质量稳定并有缓释作用;通过60例单纯疱疹性角膜炎病人的临床应用,总有效率为96．7％。结论：制剂质量稳定,对眼部无刺激,且持药时间长,是临床治疗单纯疱疹性角膜炎的较理想制剂。     

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.