石杉碱甲双层缓释片的研制及体外释药研究

目的:研制石杉碱甲双层缓释片并考察其体外释药特征。方法:缓释层以HPMC K4M为缓释骨架材料,乳糖为稀释剂;速释层以淀粉-碳酸钙为稀释剂,羧甲基淀粉钠为崩解剂,压制双层片,高效液相色谱法检测释放度。结果:制备的石杉碱甲双层片速释层在1~2min崩解,呈粉末状,符合要求;缓释层的释药曲线用Higuchi方程拟合,可维持12h释药。结论:该处方下研制的石杉碱甲双层缓释片可达到既速效又长效的目的。     

盐酸二甲双胍1000mg缓释片的制备及其体外释药机制考察

目的:制备1000mg规格的盐酸二甲双胍缓释片,考察其体外释药行为并与吡格列酮二甲双胍缓释片(Actoplus MetXR)中的二甲双胍缓释部分比较。方法:用亲水骨架结合缓释膜包衣技术制备盐酸二甲双胍缓释片,以羟丙甲纤维素(HPMC)K100M为片芯缓释材料,以丙烯酸树脂(尤特奇)NE30D为缓释包衣膜,以ActoplusMetXR中的二甲双胍缓释部分(规格:1000mg)为对照药,以两者体外释放曲线比较的相似因子(f2)为考察指标,采用星点设计-效应面法优化处方,同时考察最佳处方的体外释药机制。结果:最佳处方为片芯HPMCK100M/盐酸二甲双胍为0.15(m/m)、缓释膜HPMCE6/尤特奇NE30D为0.18(m/m)、包衣增质量控制在4%～6%;缓释片体外释放行为符合Higuchi方程(r=0.9954),以扩散机制为主,类似骨架系统释药。结论:盐酸二甲双胍1000mg缓释片可以达到与对照药相似的体外释药行为。     

吸附和包埋法制备洛美沙星淀粉微球及其体外释放比较研究

目的制备盐酸洛美沙星淀粉微球,并对其体外释药模式进行研究。方法以盐酸洛美沙星为模型药物,采用吸附载药法和包埋载药法制备了载药淀粉微球,通过测定微球载药量、包封率和在不同的释放介质中的体外释放情况,对上述2种方法制备的载药微球进行质量评价。结果吸附法制备的载药微球的平均载药量为14.54μg·mg^-1,药物包封率为39.72%;而包埋载药法制备的淀粉微球的平均载药量为19.32μg·mg^-1,药物包封率为48.95%。体外释药特性研究表明它们具有缓释特性,其中包埋载药法制备的淀粉微球比吸附载药法制备的淀粉微球有更好的缓释能力,在不同的释放介质中释药曲线也有所不同,在模拟胃液中累计释药量只能得到70%;而在模拟肠液中累计释药量能达到80%以上。结论吸附载药法和包埋载药法制备的载药淀粉微球都具有缓释作用,但后者体外释药具有更明显的缓释效果。     

可注射5-氟尿嘧啶缓释凝胶体外释放及其大鼠体内药动学研究

目的:制备可注射5-氟尿嘧啶(FU)缓释凝胶,并研究其体外释药及体内药动学特征。方法:以pH/温度双重敏感生物可降解嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1为载体材料,采用物理混合法制备5-FU缓释凝胶。考察载药量和共聚物浓度对其体外释药情况的影响。采用高效液相色谱法分别测定大鼠皮下注射5-FU水溶液(参比制剂)及缓释凝胶(受试制剂)后不同时间点的血药浓度,绘制药-时曲线,计算药动学参数。结果:5-FU在载药量为0.5%,共聚物浓度为15%、20%、25%的缓释凝胶中第9天时平均累积释放百分率为89.66%、87.59%、80.85%;载药量为0.2%、0.5%、1%,共聚物浓度为25%的缓释凝胶中第9天时平均累积释放百分率为75.30%、80.85%、86.90%;参比制剂与受试制剂在大鼠体内tmax分别为0.25、0.50h,Cmax分别为72.7、31.1μg·mL-1,AUC(0～)t分别为44.5、342.4mg·h·mL-1,MRT分别为0.57、27.2h。结论:5-FU缓释凝胶中5-FU体外释放呈现Higuchi动力学特征,表现为以扩散控制型为主的释药模式;释药初期,载药量对释药速率影响较大;释药后期,共聚物浓度对释药速率影响较大。皮下注射给药后,与水溶液相比,缓释凝胶可持续释药3d,具有良好的缓释作用。     

吸附和包埋法制备洛美沙星淀粉微球及其体外释放比较研究

目的 制备盐酸洛美沙星淀粉微球,并对其体外释药模式进行研究。方法 以盐酸洛美沙星为模型药物,采用吸附载药法和包埋载药法制备了载药淀粉微球,通过测定微球载药量、包封率和在不同的释放介质中的体外释放情况,对上述2种方法制备的载药微球进行质量评价。结果 吸附法制备的载药微球的平均载药量为14.54 µg·mg^-1,药物包封率为39.72%;而包埋载药法制备的淀粉微球的平均载药量为19.32 µg·mg^-1,药物包封率为48.95%。体外释药特性研究表明它们具有缓释特性,其中包埋载药法制备的淀粉微球比吸附载药法制备的淀粉微球有更好的缓释能力,在不同的释放介质中释药曲线也有所不同,在模拟胃液中累计释药量只能得到70%;而在模拟肠液中累计释药量能达到80%以上。结论 吸附载药法和包埋载药法制备的载药淀粉微球都具有缓释作用,但后者体外释药具有更明显的缓释效果。     

乳化剂对阿司匹林微球制备的影响

目的:用溶剂挥发法以聚乳酸为载体制得阿司匹林聚乳酸微球。方法:选择不同的乳化剂,用正交设计安排实验。并以微球包埋率、载药量、表面形态、体外释放为指标优化微球的制备工艺。结果:按优化条件制得的微球包埋率39.5%,载药量7.25%,体外释药t1/2为3d。结论:制备微球缓释效果明显。     

四乙酰基葛根素双层缓释片的制备及体外释放研究

目的研制四乙酰基葛根素双层片并考察其体外释药特征。方法干法制粒压制双层片,HPLC测定四乙酰基葛根素的释放度。结果考察得到四乙酰基葛根素双层缓释片处方合理,其释药曲线用Higuchi方程拟合,可维持12h持续释放。结论四乙酰基葛根素双层缓释片的研制达到设计要求。     

阿比多尔双层缓释片的研制及体外释药

目的研制阿比多尔双层缓释片并考察其体外释药特性。方法以两种不同处方作湿法制粒、压制双层片,紫外分光光度法测定阿比多尔的释放度。结果阿比多尔双层缓释片的释药曲线用Higuchi方程或Peppas方程拟合,可维持12h持续释放。结论研制的阿比多尔双层缓释片达到设计要求。     

阿昔洛韦缓释片的工艺研究

目的　研究制备阿昔洛韦缓释片最佳工艺。方法　以羟丙甲纤维素和卡波普为亲水凝胶型骨架材料,聚乙烯吡咯烷酮溶液为黏合剂,采用湿法制粒压片,制备阿昔洛韦缓释片。进行体外释放度试验,并与普通片剂进行比较。结果与结论　研制的缓释片缓释效果良好,比普通片有更好的释药性能,药物释放规律符合Higuchi方程     

阿昔洛韦缓释片的T艺研究

目的研究制备阿昔洛韦缓释片最佳工艺.方法以羟丙甲纤维素和卡波普为亲水凝胶型骨架材料,聚乙烯吡咯烷酮溶液为黏合剂,采用湿法制粒压片,制备阿昔洛韦缓释片.进行体外释放度试验,并与普通片剂进行比较.结果与结论研制的缓释片缓释效果良好,比普通片有更好的释药性能,药物释放规律符合Higuchi方程.     

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.