盐酸罂粟碱 卵磷脂微乳的制备与透皮吸收

［摘要］目的探讨以卵磷脂微乳为载体，制备盐酸罂粟碱 卵磷脂微乳透皮给药系统，促进盐酸罂粟碱的透皮吸收。方法以伪三元相图考察油包水型微乳形成区域;以十四酸异丙酯 卵磷脂 乙醇 水作为微乳的组成部分，正交分析法筛选微乳处方，测定微乳黏度;采用智能透皮仪，大鼠离体皮肤作为透皮模型，与盐酸罂粟碱水溶液及盐酸罂粟碱 卵磷脂混悬液对比，用高效液相色谱（HPLC）法测定微乳中盐酸罂粟碱经皮渗透稳态流量。结果微乳各组分及比例对微乳粒径均有影响；盐酸罂粟碱 卵磷脂微乳的经皮渗透稳态流量大于对照组。结论微乳各组分及比例对微乳体系处方的选择具有重要意义；以微乳为载体可以促进盐酸罂粟碱的经皮渗透。     

紫外分光光度法测定盐酸罂粟碱氯化钠注射液中盐酸罂粟碱的含量

目的 　建立盐酸罂粟碱氯化钠注射液中盐酸罂粟碱合量测定方法。方法 　采用紫外分光光度法在 2 5 0 nm处测定盐酸罂粟碱的含量。结果 　盐酸罂粟碱在 0 .64 5～ 5 .80 9μg· m L- 1 范围内 ,线性关系良好 ( r=0 .9999) ;平均加样回收率为 99.66%,RSD为 0 .5 %( n=9)。结论 　本方法结果准确 ,重现性较好。     

HPLC法同时测定桂灵片中6种生物碱的含量

目的：建立HPLC法同时测定桂灵片中6种生物碱的含量。方法：采用Agilent Eclipse Plus-C18色谱柱（4.6 mm×250 mm,4.6 μm）,以乙腈（A）-0.1%磷酸（B）为流动相,梯度洗脱,流速1.0 mL·min-1,测定波长：吗啡、盐酸麻黄碱、盐酸伪麻黄碱、盐酸甲基麻黄碱、磷酸可待因210 nm;盐酸罂粟碱251 nm。结果：吗啡、盐酸麻黄碱、盐酸伪麻黄碱、盐酸甲基麻黄碱、磷酸可待因和盐酸罂粟碱进样量分别在0.001 3～0.13 μg（r=0.999 9）,0.002 5～0.25 μg（r=0.999 9）,0.002 5～0.25 μg（r=0.999 9）,0.005 4～0.27 μg（r=0.999 9）,0.002 6～0.26 μg（r=0.999 9）,0.000 5～0.11 μg（r=0.999 9）范围内呈良好线性关系,平均回收率（n=6）分别为101.6%、100.2%、95.3%、99.2%、103.5%、100.2%。结论：该方法可以用于桂灵片的质量控制。     

反相离子对色谱法测定复方双氯芬酸钠注射液的含量

目的建立反相离子对色谱法（RPIC）同时测定复方双氯芬酸钠注射液中盐酸利多卡因和双氯芬酸钠的含量。方法色谱柱：Alltech C18（150 mm×4.6 mm，5 μm）；流动相：0.05 mol·L 1磷酸二氢钠缓冲液（用磷酸调pH值2.8） 乙睛（40∶60）配制的4 mmol·L 1的庚烷磺酸钠溶液；流速1.0 mL·min 1；检测波长：213 nm；柱温：室温。结果盐酸利多卡因在20～120 μg·mL 1范围内线性关系良好（r＝0.999 9），平均回收率99.9 %，重复性实验RSD ＝0.3%(n＝6)；双氯芬酸钠在75～450 μg·mL 1范围内线性关系良好，平均回收率99.5%，重复性实验RSD为 0.5%(n＝6)。结论该法简便准确，可用于复方双氯芬酸钠注射液的含量测定。     

高效液相色谱法测定鼻嗅通喷雾剂中盐酸麻黄碱的含量

目的：建立高效液相色谱法测定鼻溴通喷雾剂中盐酸麻黄碱的含量。方法：以DiamonsilC17（4．6mm×15mm，5μm）为分析柱，甲醇-0．01mol·L^-1磷酸二氢钾（用磷酸调pH2．5）（4：96，V／V）为流动相，流速为1．0mL·min^-1，检测波长为210nm，采用外标法定量测定。结果：盐酸麻黄碱进样量在0．148～0．740μg范围内与峰面积呈良好的线性关系（r=1．0000）。平均回收率为99．39％；RSD为0．92％，（n=9）。结论：本方法操作简便，结果准确可靠，适用于鼻嗅通喷雾剂中盐酸麻黄碱含量的测定。     

高效液相色谱法测定金果榄中盐酸药根碱与盐酸巴马汀含量

［摘要］目的建立测定金果榄中盐酸药根碱与盐酸巴马汀含量的高效液相色谱法。方法采用高效液相色谱法，色谱柱：Diamonsiltm C18柱；流动相：甲醇：水（1：1）（含四甲基乙二胺3.5 mL·L 1，用磷酸调pH值至7.5）；流速：1.0 mL·min 1；检测波长：345 nm；柱温：25 ℃。结果盐酸药根碱在0.009 8～0.316 0 mg·mL 1范围内呈良好的线性关系（r=0.999 95），盐酸巴马汀在0.011 5～0.368 0 mg·mL 1范围内呈良好的线性关系（r=0.999 96）。结论采用高效液相色谱法测定金果榄中盐酸药根碱与盐酸巴马汀含量操作简便，准确，专属性强。     

泌尿宁颗粒质量标准研究

目的建立泌尿宁颗粒的质量标准。方法采用薄层色谱法对泌尿宁颗粒中的黄柏、续断进行定性鉴别；以盐酸小檗碱为对照品，采用高效液相色谱法测定盐酸小檗碱含量，色谱柱：Hppersil ODS C18 (250 mm×4.6 mm，5 μm)；流动相：乙腈 磷酸二氢钾（0.1 mol·L-1） 十二烷基硫酸钠（0.025 mol·L-1）（50：25：25）；检测波长：345 nm。结果薄层色谱中斑点清晰，易于识别；盐酸小檗碱线性范围0.019 5～0.195 0 μg（r=0.999 9），回收率99.42%，RSD=0.72%（n=5）。 结论该方法简便，灵敏度高，可有效控制泌尿宁颗粒的质量。     

高效液相色谱法测定盐酸阿比朵尔片的含量及其有关物质

目的：建立高效液相色谱（HPLC）法分离测定盐酸阿比朵尔片及其有关物质。方法：采用高效液相色谱紫外检测法测定盐酸阿比朵尔片的含量，检测波长：315nm；色谱柱：Alltech Apollo C18（5μm，250mm×4．6mm）；流动相：缓冲液为0．1％三乙胺水溶液（用磷酸调节pH2．0）-乙腈（52．5：47．5）；流速：1．0mL·min^-1，柱温：25℃，进样量：10μL。结果：在0．5～9．0mg·L^-1范围内，对照品溶液的浓度与峰面积呈良好的线性关系（r=0．9998），平均加样回收率为93．0％～99．9％，RSD为1．7％～2．4％。盐酸阿比朵尔与有关物质分离良好。结论：本法测定盐酸阿比朵尔片的含量及有关物质，方法简便，快捷，准确，专属性好。     

HPLC双波长切换法同时测定复方唑克搽剂中甲硝唑和盐酸克林霉素的含量

目的：建立高效液相色谱法同时测定复方唑克搽剂中甲硝唑和盐酸克林霉素的含量.方法：采用Thermo Syncronics C18（250 mm×4.6 mm,5 μm） 色谱柱;流动相为0.05 mol·L-1磷酸二氢钾溶液（用25%氢氧化钾调节pH至7.5）-乙腈（55：45）;流速为1.0 ml·min-1;柱温为30℃;波长切换,0～5 min在230 nm波长下测定甲硝唑含量,5～10 min在210 nm波长下测定盐酸克林霉素含量.结果：甲硝唑在198.50～1 389.50 μg·ml-1（r=0.999 9）,盐酸克林霉素在102.74～719.18 μg· ml-1（r=0.999 9）的浓度范围内呈良好的线性关系;甲硝唑的平均加样回收率为98.09%,RSD为0.37%（n=9）,盐酸克林霉素的平均加样回收率为98.05%,RSD为0.60%（n=9）.结论：该方法简便、准确,结果稳定,可为复方唑克搽剂的质量评价提供依据.     

高效液相色谱法测定注射用盐酸罂粟碱的含量

目的建立注射用盐酸罂粟碱中盐酸罂粟碱的含量测定方法。方法采用高效液相色谱法。以甲醇-0．005N庚烷磺酸钠（冰乙酸调pH值至3．0）（55：45）为流动相,用外标法按峰面积计算回收率。结果盐酸罂粟碱在1．490—11．920μg／ml范围内,线性关系良好（r=0．9999）;平均回收率为99．5,RSD为0．31（n=9）。结论高效液相色谱法操作简便快捷,测定结果准确,可用于注射用盐酸罂粟碱的含量测定和质量控制。     

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.