酮咯酸氨丁三醇海藻酸钠-壳聚糖微囊的制备

以微囊的载药量和包封率为指标,采用均匀设计,结合非线性规划法优化酮咯酸氨丁三醇海藻酸钠-壳聚糖微囊的制备工艺.结果表明,按优化条件制得的微囊包封率90%,载药量44%,在水中的释药行为符合Higuchi方程.     

酮咯酸氨丁三醇双相控释片的制备及处方优化

目的 制备酮咯酸氨丁三醇双相控释片并优化其处方。方法 采用高效液相色谱法测定样品中酮咯酸氨丁三醇含量,并计算累积释放度。单因素考察速释层中填充剂、崩解剂、润滑剂及控释层包衣增重对样品体外释放行为的影响。以速释层总质量、速释层硬脂酸镁质量占比和控释层包衣增重为考察因素,1,16 h累积释放度和硬度为评价指标,采用Box-Behnken设计-效应面法优化其双相控释片处方,并验证。结果 最优处方为速释层总质量为320 mg,以微晶纤维素（MCC）作填充剂、交联羧甲基纤维素钠（CCMC-Na）作崩解剂、4.4 mg硬脂酸镁作润滑剂,控释层包衣增重为14.4%时制备酮咯酸氨丁三醇双相控释片,所得制剂1 h累积释放度为19.14%,16 h累积释放度为93.58%,硬度为47 N。实测值与预测值偏差为-6.18%～1.08%。结论 制成的酮咯酸氨丁三醇双相控释片具有临床所需的速效及长效的双相释放特性,是一种能有效缓解疼痛的新型制剂。     

酮咯酸氨丁三醇鼻喷雾剂的制备与主药含量测定

目的：制备酮咯酸氨丁三醇鼻喷雾剂,建立其主药含量测定方法。方法采用溶解法制备酮咯酸氨丁三醇鼻喷雾剂,以高效液相色谱法测定酮咯酸氨丁三醇的含量,主要色谱条件：色谱柱：C18柱（150mm ×4.6mm,5μm）;流动相：甲醇-水-冰醋酸（55∶44∶1）;流速：1.0mL· min -1;检测波长：323nm;柱温：30℃;进样量：10μL。进行其初步稳定性考察。结果制备的酮咯酸氨丁三醇鼻喷雾剂为几乎无色的澄清液体,酮咯酸氨丁三醇检测浓度在20~100μg· mL-1范围内,线性关系良好,平均回收率为100.41%（RSD=0.24%,n=9）;初步稳定性试验表明,该制剂对光不稳定。结论该制剂制备工艺简单、可行,主药含量测定方法准确,宜避光保存。     

酮咯酸氨丁三醇眼用凝胶剂的制备工艺与质量控制

目的制备酮咯酸氨丁三醇眼用凝胶并建立其质量控制方法。方法以卡波姆-934为凝胶基质,制备了酮咯酸氨丁三醇眼用凝胶;采用高效液相色谱法测定酮咯酸氨丁三醇和有关物质的含量,色谱条件为Dikma C18柱（150 mm×4.6 mm,5μm）,以甲醇-1%冰醋酸（68：32）为流动相,柱温为室温,检测波长为323 nm,流速为1.0mL min-1;考察了酮咯酸氨丁三醇眼用凝胶的刺激性和过敏性。结果处方为卡波姆-9340.05%,玻璃酸钠0.05%,丙二醇5.0%,硼砂1.0%,苯扎氯铵0.01%,pH为6.5～8.0。酮咯酸氨丁三醇检测浓度与峰面积在0.200～0.640 mg mL-1线性关系良好（r=0.999 8）,平均回收率为100.1%（RSD=0.2%,n=9）。经加速试验和室温留样考察,其外观性状、pH值、有关物质及含量等指标均无明显变化。酮咯酸氨丁三醇眼用凝胶的局部刺激性和过敏性呈阴性。结论该凝胶剂制备工艺简单、可行,稳定性好,质量可控。     

酮咯酸氨丁三醇注射液药物利用评价标准的建立及应用

目的 建立酮咯酸氨丁三醇注射液的药物利用评价标准,并评价酮咯酸氨丁三醇注射液临床用药情况。方法 以药物说明书为基础,参照相关规范和专家共识,建立酮咯酸氨丁三醇注射液药物利用评价标准,采用回顾性研究方法,对我院2019年1月-3月50例使用酮咯酸氨丁三醇注射液的病历进行合理性评价。结果 用药指征符合率为80%,用法用量正确率为18%,疗程合理率为54%,联合用药合理率为40%,结论我院酮咯酸氨丁三醇注射液使用合格率较低,需近一步规范用药,确保患者用药的安全性。     

酮咯酸氨丁三醇临床镇痛应用的研究进展

酮咯酸氨丁三醇是一种新型非甾体抗炎药(NSAIDs),被批准用于缓解疼痛。目前国内外已经对酮咯酸氨丁三醇用于镇痛方面开展了许多研究。本文对目前酮咯酸氨丁三醇在镇痛中的使用疗效和毒副作用及酮咯酸氨丁三醇联合其他镇痛药物镇痛时的相互作用和安全性作一综述。1非甾体抗炎药药理学研究进展手术创伤能够导致明显的炎症反应,使花生四烯     

地佐辛在胸部创伤早期镇痛中的应用

目的观察地佐辛用于胸部创伤患者的早期镇痛效果。方法选择90例胸部创伤患者,完全随机分为3组：地佐辛组、盐酸哌替啶组和酮咯酸氨丁三醇组,分别肌内注射地佐辛10mg、盐酸哌替啶50mg、酮咯酸氨丁三醇60mg,1次／8h。观测3组治疗6、12、24h后的血压、心率,呼吸频率,监测脉搏血氧饱和度（SpO2）、PaO2及PaCO2值以及用药后2、4、8、12、24h各组VAS评分、BCS评分和用药后不良反应。结果治疗后6、12、24h血压、心率和PaO2、PaCO2地佐辛组和盐酸哌替啶组与酮咯酸氨丁三醇组差异有统计学意义（P〈0．05）。地佐辛组与盐酸哌替啶组患者在用药后2、4、8、12、24h各时间点的VAS评分低于酮洛酸氨丁三醇组,BCS评分高于酮咯酸氨丁三醇组,差异有统计学意义（P〈0．05）。地佐辛组患者用药后的不良反应总发生率低于盐酸哌替啶组、酮咯酸氨丁三醇组[13．0％（4／30）比43．0％（12／30）、27．0％（8／30）]（P〈0．05）。结论地佐辛在胸部创伤早期镇痛中的效果与盐酸哌替啶相当,优于酮咯酸氨丁三醇,但较盐酸哌替啶和酮咯酸氨丁三醇不良反应发生率低,其镇痛效果确切,安全性高。     

阿霉素海藻酸钠—壳聚糖微囊的释药及其体内外抗癌作用

目的：考察阿霉素海藻酸钠—壳聚糖微囊(ADM—ACM)的释药特性及其体内外抗癌作用。方法：采用乳化胶凝法制备ADM—ACM，考察微囊的释药特性。以调亡细饱的原位末端转移酶标记技术(TUNEL)及SRB活细胞染色法考察ADM—ACM的体内外抗癌活性。结果：本制备的ADM—ACM具较高的载药量，当药载比为2mg／ml，载药量达U随右。载药微囊中ADM在PBS(pH＝7．4)中突释后缓慢释放，t2h时达45％左右。体外抗癌实验表明，空白微囊对BGC—823、Bel—7402及Hela三种癌细饱株无毒性，ADM—ACM对它们的抑制作用明显优于ADM溶液。TUNEL实验显示ADM—ACM(60．85％)引起兔肢体VX2肿瘤细胞凋亡的阳性率远高于原料药(3．98％)及空白微囊(3．97％)。结论：本制备的ADM—ACM的体内外抗癌活性均显强于原料药。     

新型非甾体止痛药——酮咯酸氨丁三醇（尼松）

酮咯酸氨丁三醇是第一个可供注射的非甾体抗炎药，通过抑制前列腺素（PG）的合成而达到止痛、抗炎和退热作用，而非作用于阿片受体或激发体内阿片肽的释放。酮咯酸氨丁三醇在人体内转化为酮咯酸发挥疗效，酮咯酸能抑制花生四烯酸或胶原诱发的血小板聚集作用，     

新型壳聚糖海藻酸钠胃漂浮小丸的制备

目的采用两种新的配方制备壳聚糖-海藻酸钠小丸,考察小丸干燥方法(-50℃冷冻真空干燥和50℃烘箱干燥)对小丸漂浮及药物缓释性能的影响.方法采用锐孔凝固浴法制备壳聚糖-海藻酸钠小丸,体外释药实验考察小丸的漂浮和释药情况.结果通过改变小丸的配方,使烘干小丸在37℃人工胃液中漂浮率达到100%,雷尼替丁释放时间最长能达到5h.其漂浮效果与成本较高的冷冻干燥法相当,且药物释放时间得到延长.结论新配方制备小丸在口服胃漂浮释药上有一定应用前景.     

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.