克林霉素磷酸酯中组胺类物质检查和降压物质检查比较

摘要：目的:探讨克林霉素磷酸酯安全性检查中,以组胺类物质检查法替代降压物质检查法的可能性。方法:按照中国药典2020年版四部中的降压物质检查和组胺类物质法的规定,分别对3批克林霉素磷酸酯进行降压物质检查和组胺类物质检查,比较两种方法结果的异同。结果:根据药典标准判定,3批克林霉素磷酸酯方法适应性通过且降压物质检查和组胺类物质检查结果均符合规定。降压物质检查中有1批克林霉素磷酸酯能引起猫血压轻微下降,但在合格范围内;3批克林霉素磷酸酯均未引起豚鼠离体回肠收缩,结果符合规定。结论:克林霉素磷酸酯的组胺物质检查法可以替代克林霉素磷酸酯降压物质检查法,但克林霉素磷酸酯降压物质检查法比克林霉素组胺类物质检查法灵敏。     

降压物质检查法与组胺类物质检查法用于小牛血去蛋白提取物注射液质量控制的研究

摘 要 目的：探讨降压物质检查法和组胺类物质检查法在小牛血去蛋白提取物注射液质量控制中的适用性。方法: 对10批小牛血去蛋白提取物注射液进行降压物质检查和组胺类物质检查实验。结果: 部分供试品在实验中表现出阳性反应。两种方法得出的结果呈正相关,但部分引起麻醉猫血压下降的供试品在组胺类物质检查实验中作用不显著或相对前者有所降低。结论: 小牛血去蛋白提取物注射液有污染降压物质的风险,但部分活性杂质可能非组胺类物质,可考虑采用降压物质检查法控制产品质量。     

应用纸层析对血粉进行组胺检查

<正> 从猪血粉(或猪血)中提取的氨基酸出现降压物质,往往是因原料不新鲜,腐败分解产生了组胺。为了控制氨基酸质量,本文应用纸层析法对血粉进行组胺检查,方法简便快速。     

注射用复合辅酶降压物质检查法研究

观察注射用复合辅酶静脉给药对猫的急性降压作用,建立其降压物质检查法。方法：采用猫血压法比较10批注射用复合辅酶与组胺对照品引起的血压下降程度,确定其降压物质检查法的限值,按照该限值对22批样品进行降压物质检查。结果：注射用复合辅酶降压物质检查的限值拟定为3 IU·kg-1（按辅酶A计）,22批注射用复合辅酶中有2批不符合规定。结论：注射用复合辅酶按拟定限值检查,方法可行,建议注射用复合辅酶质量标准中增加降压物质检查。     

药品外观快速鉴别数据库的搭建

目的搭建药品外观快速鉴别数据库,并加以试用。方法研究药品外观快速鉴别技术,制定技术规范,对测试条件、图文描述、数据库更新等方面进行规范。结果依照技术规范,搭建了药品外观快速鉴别数据库,并进行了试点使用。结论所搭建的药品外观快速鉴别数据库为药品监管人员提供了便捷的工具,在实际工作中具有实用性。     

他克莫司降压物质检查法的研究

目的:建立他克莫司降压物质检查方法,提高其临床用药安全。方法:通过对他克莫司与组胺对照品引起麻醉猫血压下降程度比较研究,确定他克莫司降压物质检查法的限值。结果：降压物质检查项限值定为0.5 mg.kg-1,按此限值检查结果符合规定。结论：建立的他克莫司降压物质检查法方法可行。     

骨肽类制剂的降压物质检查

目的建立骨肽类制剂的降压物质检查法。方法根据《中华人民共和国药典》2020年版中降压物质检查法,比较骨肽类制剂与组胺对照品间、相同企业制剂与骨肽炎原液间所致的降压程度差异,并考察骨肽类原液与其制剂引起降压的相关性。结果6家生产企业的22批次样品(骨肽注射液、注射用骨肽、复方骨肽注射液、骨肽氯化钠注射液、骨瓜提取物注射液、注射用复方骨肽、注射用骨瓜提取物、注射用鹿瓜多肽)均符合规定。结论建议提高骨肽类制剂与原液的质量标准,增订降压物质检查项,以保障药品质量。     

骨肽注射液降压物质检查法研究

目的观察骨肽注射液静脉给药对猫的急性降压作用,建立其降压物质检查法。方法通过对骨肽注射液与组胺对照品引起麻醉猫血压下降程度比较的研究,确定其降压物质检查法的限值。结果将骨肽注射液临床用量的3/5作为降压物质检查的限值。按拟定限值检查,方法可行。结论建议骨肽注射液质量标准中增加降压物质检查。     

湖北省药品快速检测方法研究现状及分析

目的为全国药品快速检测方法的系统性研究提供参考。方法对湖北省2007~2009年建立的127种药品快速检测方法的技术特点进行分析。结果湖北药品快速检测技术涵盖了近红外、化学、薄层、显微等鉴别方法的研究,各类方法相互补充,可适合于现场快速鉴别。结论药品快速检测方法的研究和应用提高了监管效能,在日常监管中发挥了积极作用。     

注射用阿奇霉素及其辅料对猫血压的影响

目的本试验选择阿奇霉素（原料药）及注射用阿奇霉素的辅料一枸橼酸（助溶剂）进行降压物质检查试验,了解原料药及辅料对麻醉猫不引起血压下降的剂量,以确定注射用阿奇霉素产生降压反应的物质基础,为临床用药安全及合理使用抗生素及助溶剂的选择问题提供借鉴。方法选用猫作为实验动物,分别对三批阿奇霉素和枸橼酸进行降压物质检查试验,确定该品种对麻醉猫不引起血压下降（或血压下降未超过组胺对照品引起血压下降）的剂量,找出引起降压反应的主要物质。结果阿奇霉素以浓度为1万IU／ml,0．2ml／kg剂量静脉注射后,三批样品的降压幅度均低于磷酸组胺对照品所致血压下降幅度。枸橼酸以浓度为0．5mg／ml,1．0ml／kg剂量静脉注射后,三批样品的降压幅度均低于磷酸组胺对照品所致血压下降幅度。结论最终确定了该品种对麻醉猫不引起血压下降的剂量为阿奇霉素：2000IU／kg,枸橼酸：0．5mg／kg,其比例与制剂中两者的比例一致。提示注射用阿奇霉素的降压反应可能主要是由于枸橼酸（辅料）引起的。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

---

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.