依托泊苷肺靶向壳聚糖微球的研制

目的:制备难溶性药物依托泊苷肺靶向壳聚糖微球,并对处方工艺进行筛选.方法:以壳聚糖为分散介质,采用乳化交联法制备依托泊苷肺靶向壳聚糖微球.结果:平均粒径为13.28μm,载药量为25.30%,药物包封率为43.51%.结论:制备的微球具有良好的缓释作用和靶向性.     

用于被动肺靶向的异烟肼明胶微球的制备及表征

目的用生物可降解材料明胶制备肺靶向异烟肼明胶微球。方法用乳化法制备异烟肼明胶微球,正交试验优化其制备的因素;用差示扫描量热法（DSC）和红外光谱法（IR）确证微球的形成;用正置荧光显微镜观察微球的形态;并对异烟肼明胶微球的粒径及其分布、载药量、包封率和稳定性等进行研究。结果最佳工艺条件,重现性好,微球形态圆整,药物确己存于微球中;粒径在5.0~25.0μm的微球占总数的90%以上,平均粒径为15.63μm,达到肺靶向要求;载药量和包封率分别为14.93%和73.30%。常温放置6个月,其外观形态、大小及含量基本不变。结论制备异烟肼明胶微球的工艺简单稳定,可用于肺靶向注射剂的研究。     

肺靶向贝母素甲明胶微球的制备

目的制备肺靶向贝母素甲明胶微球,并对其理化性质进行考察。方法采用乳化—化学交联法制备贝母素甲明胶微球;采用光学显微镜对微球形态、粒度分布等进行考察;利用柱前衍生HPLC方法测微球的包封率和载药量;利用透析法考察微球体外释药特性。结果在光学显微镜下观察,微球呈球形,表面光滑,很少黏连,平均粒径10.72μm,粒径在5～25μm范围内的微球占总数的85.8%,载药量为5.128%,包封率为66.35%,体外释药具有缓释特征。结论微球的粒径、形态、载药量和包封率、体外释药性能等基本符合肺部靶向的要求。     

用于被动肺靶向的异烟肼明胶微球的制备及表征

目的 用生物可降解材料明胶制备肺靶向异烟肼明胶微球。方法 用乳化法制备异烟肼明胶微球,正交试验优化其制备的因素;用差示扫描量热法(DSC)和红外光谱法(IR)确证微球的形成;用正置荧光显微镜观察微球的形态;并对异烟肼明胶微球的粒径及其分布、载药量、包封率和稳定性等进行研究。结果 最佳工艺条件,重现性好,微球形态圆整,药物确己存于微球中;粒径在5.0~25.0 μm的微球占总数的90%以上,平均粒径为15.63 μm,达到肺靶向要求;载药量和包封率分别为14.93%和73.30%。常温放置6个月,其外观形态、大小及含量基本不变。结论 制备异烟肼明胶微球的工艺简单稳定,可用于肺靶向注射剂的研究。     

羟基喜树碱微球的制备及其小鼠体内分布研究

目的:制备肺靶向性羟基喜树碱(HCPT)微球,评价其体外释药特性及其在小鼠体内的肺靶向性。方法:以聚乳酸为主要辅料,采用溶剂挥发法制备微球,考察其粒径、包封率、载药量,比较微球及原料药的体外释药性;取12只小鼠分别尾静脉注射HCPT微球及原料药,30min后分别测定血浆及各组织的药物浓度并计算相对分布率。结果:所制微球粒径在7～30μm者达81.6%,平均粒径为(14.2±3.1)μm,包封率为72.36%,载药量为(40.6±3.6)%,微球及原料药体外释药参数T50分别为85、18min。微球给药组在肺中的药物浓度最高(32.2±2.48)μg.mL-1,相对分布率58.1%;原料药给药组在血浆中的药物浓度最高(13.52±2.58)μg.mL-1,相对分布率25.24%。结论:所制HCPT微球具有明显的缓释性及肺靶向性。     

肺靶向硫酸链霉素明胶微球的制备

目的:用生物可降解材料明胶制备肺靶向硫酸链霉素明胶微球.方法:用乳化法制备微球,正交试验设计考察影响制备工艺的因素,用扫描电子显微镜观察微球表面形态,用红外光谱分析确证含药微球的形成.并对所制备的硫酸链霉素明胶微球的粒径及其分布、载药量、包封率、稳定性等进行了研究.结果:微球形态圆整,药物确己存于微球中.微球的平均粒径为12.269 μm,粒径在5.0～25.0 μm的微球占总数的91.5%,达到肺靶向要求.载药量为42.6%,包封率为53.8%.最佳工艺条件重现性好.经37℃、RH75%放置3个月,其含量、外观形态及大小基本不变.结论:该微球制备工艺稳定,可用于肺靶向注射剂的研究.     

阿苯达唑-聚乙二醇6000固体分散体壳聚糖微球的制备与药剂学性质研究

目的:制备阿苯达唑-聚乙二醇6000(PEG)固体分散体壳聚糖微球并评价其性质。方法:以阿苯达唑-PEG固体分散体(ASD)为主体,壳聚糖为载体,采用乳化交联法制备ASD壳聚糖微球;采用电镜、红外光谱、X衍射分析法等对微球进行表征并考察其药剂学性质;动态透析法研究微球的体外释放特性。结果:所制得微球形态圆整,粒径分布均匀,平均粒径约(210±3.8)μm,载药量(6.42±0.32)%,包封率(57.86±0.74)%;红外光谱、X衍射分析法证明药物成功包载于微球中;微球在醋酸盐溶液(pH3.5)介质中的释放情况遵循Higuchi方程,可持续释放400h以上。结论:本法制备微球工艺稳定,所制微球具有显著的缓释效果。     

异烟肼明胶微球的制备

目的　制备异烟肼肺靶向明胶微球。方法　以天然可生物降解的明胶为载体材料 ,蓖麻油为油相 ,乳化法制备异烟肼明胶微球。结果　微球形态圆整 ,大小均匀 ,包封率为 46 .5 % ,载药量为 1 7.2 %。 6～ 2 6μm的微球占总数的 88.2 % ,常温放置 6个月 ,其含量、外观形态与大小基本不变。结论　本法制备的微球大部分粒径在 7～ 3 0 μm,可达到浓集于肺部的粒径要求     

肺靶向地塞米松微球的制备及体外释药

目的:研究水溶性药物地塞米松磷酸钠肺靶向微球制备工艺的优化。方法:以油/水型乳化-溶剂挥发法制备微球,考察微球的性质及肺靶向性。维持其他条件不变,内相中加入甲醇和改变外相中氯化钠的加入量后,考察微球的载药量变化。结果:所制的微球的平均粒径为(8.37±4.0)μm。突释性好,最初0.5h释药量达48.28%。各器官石蜡切片中,肺组织中有较多微球嵌顿。随着内相中加入甲醇和外相中加入氯化钠,微球载药量提高。结论:地塞米松微球有良好的肺靶向性。采用油/水型乳化-溶剂挥发法制备水溶性地塞米松微球时,内相中加入甲醇和外相中加入氯化钠有助于提高微球的载药量。     

盐酸乙胺丁醇微球的制备及体外释药性能

目的 :研究肺靶向性盐酸乙胺丁醇微球的制备和体外释药性能。方法 :采用乳化 热固化法制备微球 ,并对其形态学 ,载药量 ,体外释药等性能进行了研究。结果 :微球粒径在 12～ 42 μm ,载药量为 :(2 1.2 4± 0 .36 ) % (n =5 ) ,体外释药试验结果显示 ,盐酸乙胺丁醇微球体外释药符合Higuichi方程。 结论 :本法制得的盐酸乙胺丁醇微球具有缓释性。     

Research on Moflo XDP high speed cell sorting techniques and parameter optimization

This article aims to discuss strategies to operate Moflo XDP high-speed sorting equipment for cell sorting and optimize the instrument to run in the best operating state. Using fluorescent microspheres to quickly calibrate the position of the main liquidflow and the laser beam, adjust the amplitude and frequency according to different size CytoNozzles to find the best breakoff point, and adjust the four-way side flow to achieve the stable maintaining of the equipment, so as to quickly sort sample at high-speed. The absence of air bubbles in the sheath liquid barrel and the liquid path is the key to achieving a stable sorting-maintaining in the sorting process. The accurate calculation of the breakoff point and drop delay is the key to improve sorting efficiency and cell activity.     

湖北省原料药GMP认证中发现的主要缺陷及建议

目的：为全面理解原料药GMP认证相关标准,提高生产企业对原料药生产规范的认识和检查员的检查水平。方法：对2016年至2017年湖北省原料药现场检查中主要缺陷进行统计分析,对GMP认证中主要缺陷项目进行分类总结。结果与结论：通过共性问题,结合原料药产品的本身特点,建议加强各岗位操作人员培训,落实培训效果;合理设计厂房,加强硬件系统的改造;严格把关物料,做好溶剂回收工作;注重细节,有针对性做好确认与验证工作;文件管理系统化,记录填写规范化;引入风险管理,贯彻执行生产全过程管理;重视变更和偏差管理,提高质量意识;建立职业化检查员队伍。     

Effects of methysergide, pizotifen and ergotamine in the monkey cranial circulation.

Internal and external carotid vascular resistances were measured, in anaesthetized monkeys, to asses the direct cranial vascular effects of i.v. methysergide, pizotifen and ergotamine, and their effects on the cranial vascular responses to the constrictors 5-hydroxytryptamine and noradrenaline and the dilators histamine, prostaglandin E1 and bradykinin. Methysergide reduced responses to 5-HT, and tended to potentiate the external carotid responses to noradrenaline. Pizotifen blocked responses to histamine; it tended to reduce internal carotid responses to 5-HT, but it potentiated external carotid 5-HT responses. Ergotamine reduced responses to 5-HT and noradrenaline, but this was probably related to its cranial vasoconstrictor effects, especially in the external carotid circulation. Methysergide induced weak transient cranial vasoconstriction and pizotifen had no direct effects. These findings may be relevant to the therapeutic actions of these drugs in migraine, since the doses used approximated to those used clinically.     

Two years into the Sunshine Act: synopsis of opportunities,challenges, learnings,and potential implications

Responsible transparency helps to promote integrity between industry and researchers and has the potential to increase public trust. As part of its inevitable evolution, the Open Payments database is likely to have opportunities to increase and improve the context around the data that it reports, thus leading to a decrease in the currently encountered confusion and misinterpretation of the data. A major challenge faced by the Centers for Medicare and Medicaid Services is to make the data more informative and educational, to allow the Sunshine Act to meet its transparency goals while improving healthcare innovation.     

DIFFERENTIAL BLOCKING EFFECTS OF PRAZOSIN AND YOHIMBINE ON PRESSOR RESPONSES TO NEURONALLY RELEASED AND EXOGENOUSLY ADMINISTERED NORADRENALINE IN THE PITHED RAT

The effects of prazosin and yohimbine on pressor responses to sympathetic nerve stimulation and intravenous injections of noradrenaline, phenylephrine and clonidine were examined in pithed rats to determine the postjunctional location of alpha 2-adrenoceptors in the vascular smooth muscle. Prazosin antagonized the pressor responses to phenylephrine and to sympathetic nerve stimulation more effectively than the responses to noradrenaline and to clonidine. Yohimbine antagonized the pressor responses to noradrenaline and to clonidine more effectively than the responses to sympathetic nerve stimulation and to phenylephrine. These results suggest that alpha 2-adrenoceptors as well as alpha 1-adrenoceptors produce vasoconstriction in the rat vasculature and support the hypothesis that alpha 1-adrenoceptors are predominantly located within the neuroeffector junction in contrast to an extrajunctional location of alpha 2-adrenoceptors.     

A biologically based dynamic model for predicting the disposition of methanol and its metabolites in animals and humans.

A multicompartment biologically based dynamic model was developed to describe the time evolution of methanol and its metabolites in the whole body and in accessible biological matrices of rats, monkeys, and humans following different exposure scenarios. The dynamic of intercompartment exchanges was described mathematically by a mass balance differential equation system. The model's conceptual and functional representation was the same for rats, monkeys, and humans, but relevant published data specific to the species of interest served to determine the critical parameters of the kinetics. Simulations provided a close approximation to kinetic data available in the published literature. The average pulmonary absorption fraction of methanol was estimated to be 0.60 in rats, 0.69 in monkeys, and 0.58-0.82 in human volunteers. The corresponding average elimination half-life of absorbed methanol through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7 h. Saturation of methanol metabolism appeared to occur at a lower exposure in rats than in monkeys and humans. Also, the main species difference in the kinetics was attributed to a metabolism rate constant of whole body formaldehyde to formate estimated to be twice as high in rats as in monkeys. Inversely, in monkeys and in humans, a larger fraction of body burden of formaldehyde is rapidly transferred to a long-term component. The latter represents the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules or is taken up by the tetrahydrofolic-acid-dependent one-carbon pathway to become the building block of synthetic pathways. This model can be used to quantitatively relate methanol or its metabolites in biological matrices to the absorbed dose and tissue burden at any point in time in rats, monkeys, and humans for different exposures, thus reducing uncertainties in the dose-response relationship, and animal-to-human and exposure scenario comparisons. The model, adapted to kinetic data in human volunteers exposed acutely to methanol vapors, predicts that 8-h inhalation exposures ranging from 500 to 2000 ppm, without physical activities, are needed to increase concentrations of blood formate and urinary formic acid above mean background values reported by various authors (4.9-10.3 and 6.3-13 mg/liter, respectively). This leaves blood and urinary methanol concentrations as the most sensitive biomarkers of absorbed methanol.     

Dendrimer Delivery of Oligonucleotides

Factors limiting the pharmacological effectiveness of antisense oligonucleotides include serum stability and the fact that these agents are inefficiently transported to their sites of action in the cytoplasm and nucleus. Polyamidoamine (PAMAM) dendrimers are nonlinear polycationic cascade polymers composed of interconnected ethylenediamine molecules that are able to bind oligonucleotides electrostatically. This new complex potentially reduces metabolic degradation of phosphodiester oligonucleotides in the serum and in the lysosome. Dendrimers also have the potential to increase oligonucleotide cellular uptake, thus augmenting their pharmacological effectiveness. We studied various dendrimer generations and their ability to interact with phosphodiester oligonucleotides. Alterations in pH and in ionic strength were studied for their effects on the dendrimer-oligonucleotide complex. A fluorescent-labeled oligonucleotide was utilized to study these interactions through a fluorescence anisotropy method. Oligonucleotides complexed to dendrimers were shown to have increased metabolic stability compared with free oligonucleotides. Using tissue culture models, fluorescent-labeled oligonucleotides complexed to dendrimers were studied for their transport properties. Flow cytometry was used to monitor cell-associated fluorescence of oligonucleotides and dendrimer systems. The electrostatic oligodeoxynucleotide (ODN)-dendrimer interaction was found to be sensitive to pH and to ionic strength, with the maximal interaction occurring at low pH and ionic strength. Using fluorescent-labeled ODN, we demonstrated that the ODN-DEN complex accumulated to a greater extent than free oligonucleotides. In summary, dendrimers have the potential to increase the effectiveness of oligonucleotides by forming an electrostatic complex that is conducive to increasing metabolic stability and cellular accumulation. In this report we describe the interactions between phosphodiester ODNs and dendrimers with regard to their electrostatic interactions and their cellular uptake.     

Investigation into modification of mass transfer kinetics by acrolein in a renal biochip

In this study we present a method for investigating the effect of acrolein, a nephrotoxic and urotoxic metabolite of the anticancerous prodrugs ifosfamide and cyclophosphamide, in a blood-renal barrier biochip. The real time monitoring of mass transfers of caffeine, vitamin B12 and albumin in the biochip was performed thanks to an in vitro dialysis method. The diffusion coefficients of the solutes and their dialysance from the apical to the basolateral compartments were found to be molecular weight and cell-membrane dependent, thus demonstrating the cell-barrier functionality. The toxicity induced by the acrolein led to modifications to mass transfer properties which appeared to be acrolein dose, time and solute molecular weight dependent. Solute mass transfer across the cell layer increased with acrolein concentrations. The sensitivity of this analysis method contributes to identify the mass transfer properties and to monitor the modification to the renal parameter when submitted to toxic cell compounds. The results provide the foundation for exploring kidney behavior in response to drugs thanks to a blood-tissue barrier model using a technique based on in vitro dialysis and real time analysis.     

Applying health technology assessment to pharmaceutical care: pitfalls and future directions

It has been argued in previous issues of this journal that health technology assessment can be used as a tool to assess the efficiency of pharmaceutical care by linking its impact on clinical and humanistic outcomes to the resources required to achieve these outcomes. Additionally, as policy-makers appreciate the need to evaluate projects on the basis of their costs and benefits, the application of health technology assessment to pharmaceutical care may serve as a way of communicating with policy-makers and informing policy on pharmaceutical care.This article elaborates on this idea by arguing that policy-makers will be more likely to appreciate the value of pharmaceutical care if researchers pay more attention to some methodological principles underlying health technology assessment in the context of pharmaceutical care, and if they take into account the decision-making context facing policy-makers. In order to raise the methodological quality of studies, researchers need to take care to define better the pharmaceutical care intervention; to evaluate the costs of the intervention and its impact on the utilization of other health services; and to aggregate the various clinical and humanistic outcome measures that are commonly used in this type of research. In order to increase the usefulness of study findings to policy-makers, researchers need to identify the multiple objectives that policy-makers pursue, and show how study findings will aid policy-makers in attaining these objectives.     

加强医院药品的质量管理

加强药品质量管理,为医院提高医疗质量,保证患者用药安全提供了有效保障。根据医疗、科研的实际需要,以中华人民共和国《药品管理法》和《医院药剂管理办法》的规定,加强医院药剂管理,严把药品采购、保管、使用关。通过加强医院药品质量管理,贯彻优质、合理、高效、低耗的原则,使医院达到有效、安全、经济、方便地使用药品。加强医院药品的质量管理,对促进医院健康、稳定的发展具有重要意义。