克林霉素磷酸酯注射液对一次性输液器中邻苯二甲酸二（2-乙基）己酯的溶出研究

摘要：目的:考察克林霉素磷酸酯注射液对一次性使用输液器中苯二甲酸二（2-乙基）己酯（DEHP）的溶出规律。方法:模拟临床使用克林霉素磷酸酯注射液经一次性输液器静脉滴注,UPLC-MS/MS法测定流出液中DEHP的溶出量。同时考察药物浓度和滴注时间对于DEHP溶出的影响,确定克林霉素磷酸酯注射液促进DEHP溶出的因素。结果:克林霉素磷酸酯注射液中的苯甲醇是促进一次性输液器中DEHP溶出的主要因素,并且随着苯甲醇浓度升高和滴注时间的延长,DEHP的溶出量相应增加。结论:苯甲醇促进了一次性输液器中DEHP的溶出,溶出量与苯甲醇浓度和滴注时间呈正相关。     

3种不同材质输液器对丁苯酞氯化钠注射液中丁苯酞的吸附考察

摘 要 目的：考察3种不同材质输液器对丁苯酞氯化钠注射液的吸附性,为临床选择输液器提供参考。方法: 采用HPLC法,色谱柱：Eclipse XDB C₁₈柱（150 mm×4.6 mm,5 μm）;流动相：甲醇-0.05 mol·L^-1磷酸二氢钾溶液（60∶40）;流速：1.0 ml·min^-1;检测波长：280 nm;柱温：30℃;进样量为10 μl。结果: 丁苯酞在60.90～487.20 μg·ml^-1浓度范围内呈良好的线性关系（r=0.999 9）,平均回收率为99.9%（RSD=0.3%,n9）。聚氯乙烯输液器对丁苯酞的吸附最为严重,聚丙烯和聚乙烯输液器对丁苯酞的吸附较少。结论:采用的HPLC法简便、准确、灵敏度高,可用于丁苯酞的含量测定。聚氯乙烯输液器不适用于丁苯酞氯化钠注射液的静脉滴注,建议选择聚丙烯和聚乙烯输液器。     

细辛脑注射液和注射用细辛脑降压作用的研究

目的:考查细辛脑注射液和注射用细辛脑的降压作用,补充完善其标准中安全性检查项目。方法:按照《中国药典》2010年版二部附录降压物质检查法进行试验,成品的检查剂量为临床一次最大用量0.5 mg·kg^-1,辅料的检查剂量为不同企业制剂中添加的最大剂量。结果:细辛脑注射液和注射用细辛脑均有一定的降压作用,但均不大于对照品的降压作用;辅料中丙二醇有较明显降压作用,聚乙二醇400和聚山梨酯80对血压均有一定的影响;丙二醇、聚山梨酯80及乙醇联合添加对血压有一定影响。结论:细辛脑注射液和注射用细辛脑应建立降压物质检查法,以更好地控制产品质量。     

广东省四地区二级以上医院部分医务人员一次性输液器认知度调查

摘 要 目的:了解广东省医疗机构医务人员使用一次性输液器的认知现状,为一次性输液器安全使用提供参考。方法：自行设计问卷。对广东省四个地区的医疗机构175名医务人员进行调查。结果：参与调查的医务人员对一次性输液器导致不良事件的知晓率为46.29%;对精密输液器和避光输液器的知晓率分别为48.00%和48.29%;对含增塑剂的PVC输液器不能用于新生儿、青春期前男性、怀孕期和哺乳期妇女的知晓率分别为27.43%、12.00%和34.29%。71.43%的医务人员希望在以后的工作中获得一次性输液器相关知识培训。结论： 医务人员对一次性输液器的认知情况不容乐观,监管部门应加大一次性输液器相关知识的培训力度,提高医务人员对一次性输液器不良事件监测的认知度,提高监测能力,减少不良事件的发生。     

HPLC测定四味珍层冰硼滴眼液中苯氧乙醇含量

目的 采用HPLC测定四味珍层冰硼滴眼液中苯氧乙醇含量。方法 采用DIKMA Diamonsil C₁₈色谱柱（4.6 mm×250 mm,5 μm）;流动相：甲醇-水（50∶50）;流速： 1.0 mL·min^-1;检测波长： 268 nm;柱温： 30℃。结果 苯氧乙醇在浓度5.43~163.04 μg·mL^-1内线性关系良好（r=1.000 0）,平均回收率为100.3%,RSD为1.1%。结论 该法简便、准确、精密度高,适用于四味珍层冰硼滴眼液中苯氧乙醇含量测定。     

UPLC-MS测定薄膜衣片中16种邻苯二甲酸酯类塑化剂

目的 建立UPLC-MS测定薄膜衣片中16种邻苯二甲酸酯类塑化剂含量的方法。方法 采用甲醇提取,Waters ACQUITY UPLC BEH C₁₈色谱柱（2.1 mm×50 mm,1.7 μm）同时串联Waters PFCs Isolator捕集柱（2.1 mm×50 mm）,以0.1%甲酸水溶液和甲醇为流动相,梯度洗脱,流速：0.4 mL·min^-1;采用电喷雾离子源,正离子模式,多反应监测模式检测。结果 在实验条件下,16种塑化剂分离良好;DBP、DIBP检测限为0.5 mg·kg^-1,其余14种塑化剂检测限为0.1 mg·kg^-1;DBP、DIBP在0.20~1.00 μg·mL^-1内,其余14种塑化剂在0.05~1.00 μg·mL^-1内,峰面积与检测浓度之间的线性关系良好（r ≥ 0.995）;平均回收率均在83%~115%之间。结论 该方法操作简单、快速、准确,适用于薄膜衣片中邻苯二甲酸酯类塑化剂的测定。     

预灌封注射器橡胶活塞表面硅油提取及向甲氨蝶呤注射液中迁移的研究

目的 研究预灌封注射器的橡胶活塞表面硅油的使用量，以及硅油在甲氨蝶呤注射液中的迁移量。方法 采用傅里叶变换红外光谱法测定预灌封注射器中溴化丁基橡胶活塞表面的硅油含量，并采用电感耦合等离子体质谱法测定甲氨蝶呤注射液中的硅油迁移量。结果 活塞表面的硅油含量为每个0.191 mg，0.5，0.2，0.15 mL规格甲氨蝶呤注射液的最大迁移量分别为2.65，1.26，1.04 μg。结论 傅里叶变换红外光谱法和电感耦合等离子体质谱法能分别快速测定橡胶活塞表面的硅油量和硅油在制剂中的迁移量。     

HPLC法测定安乃近注射液中苯甲醇的含量

摘 要 目的：建立高效液相色谱法测定安乃近注射液中苯甲醇的含量。方法: 采用Xtimate C18（250 mm×4.6 mm,5 μm）柱,流动相为磷酸盐缓冲液（取磷酸二氢钠6.0 g,加水1 000 ml,加三乙胺1 ml,用氢氧化钠溶液调pH至7.0） 甲醇（75∶〖KG-*2〗25）,流速为1.0 ml·min^-1,检测波长为254 nm,柱温：30℃,进样量：5 μl。结果:苯甲醇检测线性范围为76.88～269.08 μg·ml^-1（r=0.998 5）,平均回收率为98.77%（RSD=0.77%,n=9）。结论:该方法准确、重复性好,可用于安乃近注射液中苯甲醇含量的测定。     

HPLC法检测醋酸奥曲肽注射剂中5种抑菌剂

目的：检测醋酸奥曲肽注射剂中是否添加苯酚、苯甲醇、三氯叔丁醇、对羟基苯甲酸甲酯及对羟基苯甲酸丙酯5种抑菌剂。方法：采用C18（L）（4.6 mm×250 mm,5 μm）色谱柱,流动相A为水,流动相B为甲醇,梯度洗脱,流速为1.0 mL·min^-1,柱温30℃,检测波长为220 nm及256 nm。结果：苯酚、苯甲醇、三氯叔丁醇、对羟基苯甲酸甲酯及对羟基苯甲酸丙酯各峰均分离良好;苯酚在1.29~258.60 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为100.0%（n=9）;苯甲醇在2.72~544.20 μg·mL^-1范围内线性关系良好（r=0.9997）,平均回收率为100.3%（n=9）;三氯叔丁醇在9.95~1990.00 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为100.9%（n=9）;对羟基苯甲酸甲酯在0.27~53.80 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为100.5%（n=9）;对羟基苯甲酸丙酯在0.26~52.00 μg·mL^-1范围内线性关系良好（r=1.000）,平均回收率为99.4%（n=9）;91批醋酸奥曲肽注射剂中均未检出5种抑菌剂。结论：该方法准确、灵敏、简便,可用于醋酸奥曲肽注射剂中苯酚、苯甲醇、三氯叔丁醇、对羟基苯甲酸甲酯及对羟基苯甲酸丙酯5种抑菌剂的检查。     

分散相液相微萃取法测定通过输液管后注射液中的邻苯二甲酸酯增塑剂含量

目的 采用分散相液相微萃取与GC-MS结合,建立测定通过输液管后注射液中6种邻苯二甲酸酯含量的方法。方法 将30 μL苯甲酸苄酯(内标)的甲苯溶液和20 μL十六烷基三甲基溴化铵溶液快速注入到5.0 mL样品溶液中,旋涡振荡1 min,4 000 r·min^-1离心5 min。弃去水相,使有机相聚集于离心管底部,取1.0 μL萃取液进行CG-MS分析。结果 6种邻苯二甲酸酯的富集倍数为174~280,检测限为(S/N=3)0.007~0.04 ng·mL^-1,加样回收率为97.8%~101.2%,RSD为0.44%~0.93%。在某些通过输液管的注射液中检出DBP和DEHP。结论 本方法灵敏、简便、快速,适用于通过输液管后注射液中微量邻苯二甲酸酯的检测。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.