Preparation and characterization of intravenously injectable nimodipine nanosuspension

The purpose of this study was to develop an alternative, improved and better tolerated injectable nimodipine nanosuspension compared with commercially available ethanol solution. In this study, nimodipine nanosuspension was prepared by high-pressure homogenization (HPH). The effects of the production parameters such as pressure, cycle numbers and crushing principles on the mean particle size, 99% diameter and polydispersity of the nanosuspension were investigated. Characterization of the product was performed by scanning electron microscope (SEM) and differential scanning calorimeter (DSC). The safety of the nimodipine nanosuspension was discussed with special attention to contamination by microparticles and the increase in saturation solubility C_s. Irritability study in rabbits showed that this formulation provided less local irritation and phlebitis risks than the commercial ethanol product, which represented a promising new drug formulation for intravenous therapy of subarachnoid hemorrhage (SAH)-related vasospasm.     

Solid form selection of zwitterionic 5-HT4 receptor agonist

From discovery synthesis of a zwitterionic pharmaceutical compound, 4-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylic acid (compound A), two anhydrous ZW-I and ZW-II and two hydrate forms ZW-III and ZW-IV were identified. Although stable form ZW-I was chemically stable at 70 °C/75% RH for 10 days, it was transformed to hydrate form ZW-IV under ambient conditions within a few days, taking up water from atmospheric moisture. In order to select a solid form for further investigation, solid-state characterization, salt screening on 96-well plate, stable polymorph and hydrate screening and physical stability were performed. Based on the results of the salt screening, besylate, camsylate, hemi-edisylate, hemifumarate, monosuccinate salts of compound A were prepared, and their polymorphism and chemical and physical stability were evaluated. From the viewpoint of stability and manufacturability, a stable form of besylate salt (BSA-I), which had two anhydrous forms BSA-I and BSA-II and hydrate form BSA-III, was selected as a solid form. BSA-I was quite stable at high relative humidity and provided significant improvement of physical stability compared with ZW-I.     

微片的特点和研究进展

在口服缓控释给药系统中,与单元型制剂相比,多单元型制剂的药物高度分散在胃肠道内,可以减少药物突释、提高用药安全性,还可以准确控制剂量、提高患者顺应性。多单元型给药系统包括颗粒、微球、微丸和微片等。该文主要介绍微片的特点和近年来的一些研究进展。     

Utilization of ionotropic gelation technique for bioavailability enhancement of cinnarizine: in-vitro optimization and in-vivo performance in human

Gastro retentive drug delivery system techniques were adopted to deliver drugs having narrow absorption window from a particular site in the GIT. Therefore, gastro retentive dosage forms were retained in the stomach, thus improving absorption and bioavailability would be improved consequently. In this study, cinnarizine (CNZ) was employed as the model drug. CNZ is a poorly soluble basic drug, suffering from low and erratic bioavailability. This is attributed to its pH-dependant solubility (highly soluble at pH?<?4). CNZ is characterized by short half-life (3–6?h). Accordingly, floating CNZ emulsion gel calcium pectinate beads were developed. A mixture design was employed to study the effect of the percent of LM pectin (A), the percent of GMO (B) and the percent of Labrafac Lipophile (C) simultaneously on the percent of drug released and loaded. The optimized floating CNZ emulsion gel calcium pectinate beads and Stugeron® (the marketed reference product) were compared through a pharmacokinetic study carried on healthy human volunteers. Fortunately, simple floating CNZ emulsion gel calcium pectinate beads were prepared with zero-order release profile for 12?h. A promising in-vivo CNZ controlled release dosage form with higher bioavailability, when compared to once daily administration of Stugeron® tablets was achieved.     

番泻叶药理作用研究进展

番泻叶主要含有蒽醌类、黄酮类、多糖和挥发油等化学物质,具有泻下、抑菌、止血、调节免疫功能与抗氧化等作用。本文通过对番泻叶的化学成分、药理作用、临床应用与新剂型研究等方面的相关文献进行归纳,为番泻叶的研究与临床应用提供参考。     

Handover from paramedics: Observations and emergency department clinician perceptions

Objectives: 1. To evaluate emergency clinician attitudes towards handover from prehospital paramedics. 2. To determine the content and methods of paramedic handover delivery to emergency clinicians. Methods: Exploratory study comprising questionnaire of emergency clinicians and observation of paramedic‐to‐emergency clinician handover with associated survey at an adult tertiary referral hospital with approximately 12 000 ambulance arrivals of 37 000 annual attendances. Results: Emergency staff found handover from paramedics on patient conditions relevant, especially for altered consciousness (94%, 95% CI 83.5–98.6), trauma (90%, 95% CI 82.0–98.4) and chest pain (88%, 95% CI 79.0–97.0), but less so for behavioural disturbance (67%, 95% CI 53.7–79.5). A total of 621 handovers from 311 ambulance arrivals were observed. Most arrivals (81%, 95% CI 76.4–85.4) were not preceded by prehospital communication. Paramedics handed over twice 91% of the time (95% CI 88.2–94.4). Doctors received direct paramedic handover for 12% (95% CI 8.0–15.1) of ambulance arrivals, including 19 team handovers, whereas triage nurses took 97% (95% CI 95.6–99.2) and attending nurses, 91% (95% CI 87.5–93.9). Fifty per cent (95% CI 42.7–57.3) of emergency clinicians referred to ambulance sheets. Handover information was perceived to be useful and accurate in more than 80% of instances. Verbal handover occurred before ambulance sheet completion for 78% (95% CI 73.5–82.7). Conclusion: Although there is satisfaction in paramedic handover, prehospital notification and emergency physician contact with paramedics is uncommon for low acuity patients, who constitute the majority of ambulance attendances and hospital admissions. Scope for improved direct doctor–paramedic communication exists.     

检测记录单在SARS防护中的作用

目的 :用简便易操作的方法 ,完成严重急性呼吸综合征 (severeacuterespiratorysyndrome ,SARS)时期的流行病学记录和工作质量监督。方法 :采用表格记录的方法 ,科室督导员全权负责 ,定期与随机查、普查与重点查结合 ,即时反馈与每周小结相结合。结果 :达到全面、严格的控制。全院人员实现零感染 ,病人无院内交叉感染。结论 :表格记录的方法任何时候不可替代 ,在严重急性呼吸综合征疫情分析中起到了排查和约束作用 ,对护理决策产生重要影响。     

5种皮肤消毒剂对绿脓杆菌杀灭及诱导L型作用的实验观察

经试验，以含５００ｍｇ／Ｌ有效碘的碘伏作用１～５ｍｉｎ或含１０００ｍｇ／Ｌ有效碘者作用１ｍｉｎ，以及０１％新洁尔灭溶液作用５～１５ｍｉｎ，均可诱导绿脓杆菌形成Ｌ型。两种消毒剂诱导的Ｌ型，菌落特征、菌体形态、革兰氏染色与生化反应等均基本一致，传１～２代可恢复亲代特征。     

A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins

BACKGROUND: Experimental evidence from rodent models indicates that blood can contain transmissible spongiform encephalopathy (TSE) infectivity, which suggests a potential risk for TSE transmission via proteins isolated from human plasma. Because methods that can reduce TSE infectivity typically are detrimental to protein function, infectivity must be removed to ensure the safety of these therapeutic proteins. Animal bioassays are conventionally used to detect infectivity, but the pathogenic form of the prion protein (PrP^Sc) can serve as a marker for TSE infectivity. STUDY DESIGN AND METHODS: Seven plasma protein‐purification steps were performed after the plasma intermediates were spiked with TSE‐infected material. Resulting fractions were analyzed for PrP^Sc by using a Western blot assay and for TSE infectivity by using an animal bioassay. Western blots were quantitated by an endpoint dilution analysis, and infectivity titers were calculated by the Spearman‐Kärber method. RESULTS: PrP^Sc partitioning paralleled TSE infectivity partitioning, regardless of the nature of the protein‐purification step. The detection ranges for PrP^Sc and infectivity were 0 to 5.3 log and 1.1 to 8.9 log median infectious dose per unit, respectively. Clearance of PrP^Sc and infectivity ranged from 1.0 to 6.0 log. CONCLUSION: Purification steps for isolating therapeutic proteins from human plasma showed the removal of both PrP^Sc and TSE infectivity. PrP^Sc partitioning coincided with infectivity partitioning, which showed a close relationship between PrP^Sc and TSE infectivity. By exploiting this association, the in vitro Western blot assay for PrP^Sc was valuable for estimating the partitioning of TSE infectivity during plasma protein purification.     

Excel自动报告表格在消毒产品实验数据处理中的应用

目的探索Excel自动报告表格在消毒产品实验报告数据处理中应用的可行性,以加快试验数据处理速度并提高其准确性。方法结合实际检验结果,对实验数据进行自动运算处理,在表格中录入实验数据生成报告结果。结果经采用Excel自动报告表格直接在计算机上进行数据处理,可按程序对中和剂鉴定试验结果、杀(抑)菌试验数据作出准确、快速报告。在报告表中自动生成各种平均值、杀灭率、对数值及误差率等数据。结论采用Excel电子表格插入运算法,能提高消毒试验报告的准确性,极大缩短运算处理过程,可以用于消毒效果评价实践。