4种常用中药注射液不同浓度对不溶性微粒的影响

摘 要 目的：考察4 种常用中药注射液与0.9%氯化钠注射液不同浓度配伍的不溶性微粒数变化,为临床选择药物浓度提供参考。方法: 将复方苦参注射液、疏血通注射液、鹿瓜多肽注射液、注射用红花黄色素用0.9%氯化钠注射液制成低浓度和高浓度溶液,按照中国药典2015版第四部通则0903不溶性微粒检查法测定其配伍前与配伍后0,2,4,5 h的不溶性微粒数。结果: 4种中药注射剂原液和0.9%氯化钠注射液不溶性微粒符合要求;4种中药注射剂不同浓度下≥25 μm不溶性微粒数量都很少,几乎不随时间变化;4种中药注射剂≥10 μm不溶性微粒数总体呈现高浓度输液中的微粒数略多于低浓度,随时间变化趋势各不相同。结论:高浓度中药注射剂输液中≥10 μm不溶性微粒数较低浓度中药注射剂输液略多,建议临床按照说明书规定的浓度进行药物稀释,并尽快使用。     

医院静脉药物配置条件下丹参多酚酸盐输液的不溶性微粒考察

目的 测定在医院静脉药物配置条件下注射用丹参多酚酸盐输液中的不溶性微粒,考察各配置条件(浓度、溶媒、静置时间)对其输液的不溶性微粒影响。方法 根据统计的处方,在医院静脉药物配置中心完成输液的配置,并采用中国药典2010年版规定的不溶性微粒检查法测定丹参多酚酸盐进入患者体内前输液中不溶性微粒的数量。结果 选用5%葡萄糖或0.9%氯化钠注射液作溶媒,输液在8 h内符合中国药典对不溶性微粒数目的要求;输液中的较小微粒(粒径≥2 μm)数目明显比较大微粒(粒径≥10 μm)的数目多,差异具有统计学意义(P<0.05);配制的高浓度(0.8 g·L^-1)输液较低浓度(0.4 g·L^-1)输液更易产生较多不溶性微粒。结论 医院在配制丹参多酚酸盐输液时应选用5%葡萄糖或0.9%氯化钠注射液作溶媒,在按照说明书规定的用法用量情况下应选择较低的配置浓度(0.4 g·L^-1),输液配制完毕后应尽快用完。     

注射用肌氨肽苷与不同输液配伍的稳定性考察

摘 要 目的：考察注射用肌氨肽苷与不同输液配伍后的稳定性,为临床应用提供依据。方法: 考察注射用肌氨肽苷分别与0.9%氯化钠注射液、5%葡萄糖注射液、10%葡萄糖注射液、葡萄糖氯化钠注射液的配伍溶液在0,0.5,1,2,4,8 h时的外观、pH、不溶性微粒数及次黄嘌呤和多肽含量的变化情况。 结果: 不同配物溶液均为澄明液体,pH无明显变化,次黄嘌呤和多肽的含量均符合要求。与10%葡萄糖注射液配伍时,≥10 μm的不溶性微粒数最少,符合中国药典2015年版四部规定,与0.9%氯化钠注射液、5%葡萄糖注射液和葡萄糖氯化钠注射液配伍时,个别时间点的≥10 μm不溶性微粒数不符合规定;各配伍溶液≥25 μm的不溶性微粒数均符合规定。结论:注射用肌氨肽苷最适配伍溶媒为10%葡萄糖注射液。     

不同基础输液与4种临床常用注射剂配伍前后不溶性微粒的测定分析

目的：考察不同基础输液和4种临床常用注射剂配伍前后不溶性微粒的差异。方法：选取临床常用的3个厂家（内封式聚丙烯输液袋BFS、双层无菌软袋、直立式聚丙烯输液袋，编号厂家1、2、3）的0.9%氯化钠注射液（NS）和5%葡萄糖注射液（5% GS），测定不同基础输液与临床常用注射剂配伍前后2 μm 以上不溶性微粒数量。NS与注射用盐酸氨溴索配伍，5% GS与注射用地塞米松磷酸钠配伍。另外将多索茶碱注射液和奥拉西坦注射液分别与上述2种基础输液配伍）。结果：空白输液中厂家1输液中不溶性微粒最少，厂家3最多。与注射剂配伍后，无论NS还是5%GS，厂家1输液中不溶性微粒最少，厂家3显著高于其他两家，尤其是2~5 μm，5~10 μm小粒径不溶性微粒。多索茶碱和奥拉西坦与同一厂家的5%GS和NS配伍后不溶性微粒数量相近，说明临床使用中与二者配伍皆宜。结论：不同基础输液与临床常用药配伍后不溶性微粒数量具有显著差异，提示生产企业应提高输液产品的质量控制标准，医院临床治疗需重视输液产品的遴选，为输液临床使用安全性提供保障。     

过滤对一种IgG2亚型EGFR单抗中不溶性微粒的影响

目的：探讨过滤操作对一种免疫球蛋白G2（immunoglobin G2,IgG2）亚型表皮生长因子受体（epidermal growth factor receptor,EGFR）单克隆抗体（单抗）生物类似药（similar biotherapeutic product,SBP）候选药中不溶性微粒的影响。方法：利用微流数字成像（microflow digital imaging,MDI）技术对某厂家生产的IgG2亚型EGFR单抗SBP候选药与其原研药（reference biotherapeutic product,RBP）中不同粒径的不溶性微粒进行比较;采用0.22 μm的滤器对EGFR单抗SBP候选药进行过滤,并采用MDI法立即对不同粒径和性质的不溶性微粒进行检测和分析;再将过滤后的EGFR单抗SBP候选药在室温静置2 h,并采用MDI法对不同粒径和性质的不溶性微粒进行检测和分析。结果：某IgG2亚型EGFR单抗SBP候选药中不同粒径的不溶性微粒数量明显高于RBP;用0.22 μm的滤器过滤后,EGFR单抗SBP候选药中的不溶性微粒数由8.51×10⁵粒·mL^-1降为1.52×10⁴粒·mL^-1,且主要成分蛋白聚体、气泡和纤维均明显减少;室温静置2 h后,其中的不溶性微粒数由1.52×10⁴粒·mL^-1增加至3.23×10⁴粒·mL^-1,且增加的微粒主要为蛋白聚体。结论：与原研药相比,该EGFR单抗SBP候选药蛋白聚体水平较高,过滤后有明显改善,但随着放置时间延长,蛋白聚体含量又有明显增加。这提示我们需加强研发,以提高SBP候选药的产品质量、安全性和有效性。     

PVC软包装4:1输液的不溶性微粒考察

目的考察PVC软包装41输液的不溶性微粒.方法应用ZWF-4DⅡ型注射液微粒分析仪测定41输液的≥25μm、≥10μm、≥5 μm和≥2 μm的4个通道不溶性微粒数.结果5批PVC软包装100ml的41输液在≥25 μm、≥10 μm、≥5μm和≥2 μm的4个通道不溶性微粒数(-x±s,n=5)分别为(0.9±0.7)粒/ml、(10.0±5.0)粒/ml、(63.5±16.2)粒/ml和(2 047 3±634 6)粒/ml.结论PVC软包装41输液的≥10 μm和≥25 μm不溶性微粒符合<中国药典>的要求,≥5 μm的不溶性微粒符合<英国药典>的要求,但其≥2 μm的不溶性微粒不符合<英国药典>的要求,提示输液中≥2 μm的不溶性微粒偏高应引起医药界的重视.     

PVC软包装4∶1输液的不溶性微粒考察

目的　考察PVC软包装 4∶ 1输液的不溶性微粒。方法　应用ZWF - 4DⅡ型注射液微粒分析仪测定 4∶ 1输液的≥ 2 5μm、≥ 10 μm、≥ 5 μm和≥ 2 μm的 4个通道不溶性微粒数。结果　 5批PVC软包装 10 0ml的 4 ∶1输液在≥ 2 5 μm、≥ 10 μm、≥ 5 μm和≥ 2 μm的 4个通道不溶性微粒数 ( x±s,n =5 )分别为 (0 .9± 0 .7)粒 /ml、(10 .0± 5 .0 )粒 /ml、(6 3.5± 16 .2 )粒 /ml和 (2 0 4 7.3± 6 34.6 )粒 /ml。结论　PVC软包装 4∶ 1输液的≥ 10 μm和≥ 2 5 μm不溶性微粒符合《中国药典》的要求 ,≥ 5 μm的不溶性微粒符合《英国药典》的要求 ,但其≥ 2 μm的不溶性微粒不符合《英国药典》的要求 ,提示输液中≥ 2 μm的不溶性微粒偏高应引起医药界的重视     

非药物配伍引起输液不溶性微粒变化的探讨

目的 考察一次性使用无菌注射器、加药过程及加药环境对输液不溶性微粒的影响.方法 取一次性使用无菌注射器、一次性使用输液器及5%葡萄糖注射液,分别在病房治疗室和净化洁净室,模拟加药及输液操作制备样品,按《中华人民共和国药典》(2005年版二部),以光阻法测定样品中的不溶性微粒.结果 与未模拟加药及输液操作前的输液比较,在病房治疗室和净化洁净室制备的样品中,≥10 μm 的不溶性微粒均有显著增加(P＜0.05),≥25 μm 的不溶性微粒均增加不明显(P＞0.05);于病房治疗室制备的样品与净化洁净室制备的样品比较,≥10 μm 的不溶性微粒增加显著(P＜0.05),≥25 μm 的不溶性微粒增加不明显(P＞0.05).结论 一次性使用无菌注射器、加药过程及病房治疗室中加药,可使输液中≥10 μm 的不溶性微粒明显增加.     

PVC软包装4:1输液的不溶性微粒考察

目的考察PVC软包装4:1输液的不溶性微粒.方法应用ZWF-4DⅡ型注射液微粒分析仪测定4:1输液的≥25μm、≥10μm、≥5 μm和≥2 μm的4个通道不溶性微粒数.结果5批PVC软包装100ml的4:1输液在≥25 μm、≥10 μm、≥5μm和≥2 μm的4个通道不溶性微粒数(-x±s,n=5)分别为(0.9±0.7)粒/ml、(10.0±5.0)粒/ml、(63.5±16.2)粒/ml和(2 047 3±634 6)粒/ml.结论PVC软包装4:1输液的≥10 μm和≥25 μm不溶性微粒符合<中国药典>的要求,≥5 μm的不溶性微粒符合<英国药典>的要求,但其≥2 μm的不溶性微粒不符合<英国药典>的要求,提示输液中≥2 μm的不溶性微粒偏高应引起医药界的重视.     

折光率对微流成像法检测蛋白制剂不溶性微粒的影响

目的：蛋白制剂中不溶性微粒的含量是衡量样品质量的重要指标之一,为了更为准确地检测不溶性微粒的含量和粒径,本研究探讨了溶液折光率对于微流成像系统检测不溶性微粒的影响。方法：本研究以牛血清白蛋白（BSA）为例,通过常见的外界刺激条件（冷冻-解冻）制备高浓度的蛋白质不溶性微粒,并将此微粒稀释至不同折光率的溶液（由PEG1000、海藻糖制备）中,利用微流成像系统检测不溶性微粒的含量。结果：当溶液的折光率接近蛋白质不溶性微粒折光率时,利用微流成像技术检测的不溶性微粒含量低于实际的微粒含量。此外,随着溶液折光率的增加,采用微流成像技术检测出的不溶性微粒的粒径也随之减小。结论：蛋白质溶液的折光率发生改变,会影响利用微流成像技术检测不溶性微粒的准确性。因此,利用微流成像技术检测蛋白制剂中不溶性微粒时,需要考虑到制剂处方的折光率对于检测不溶性微粒的影响,必要时可以采用稀释的方法降低折光率对蛋白质颗粒的屏蔽作用。     

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.