Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization

The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study.     

延长不同实验步骤温育时间对HBsAg酶免结果的影响

目的探讨延长不同实验步骤温育时间对乙肝表面抗原(hepatitis B surface antigen,HBs Ag)酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)结果的影响,从而保证检测结果的准确性和精确性。方法在其他实验参数不变的条件下,通过延长加酶前、加酶后、显色等步骤的温育时间,分别对强阳性、中阳性、弱阳性、阴性标本进行检测,所得数据采用SPSS 17.0软件进行相关分析。结果 1延长加酶前温育时间对强阳性和弱阳性标本的影响差异具有统计学意义,强阳性标本吸光度明显下降,弱阳性标本明显加强,并与延长的时间密切相关。2延长加酶后温育时间对各标本吸光度(阴性除外)影响最显著。3延长显色时间对实验结果影响并不明显。4延长各反应步骤温育时间对HBs Ag阴性标本吸光度影响均无统计学意义。结论选择正确的步骤适当延长温育时间可提高ELISA实验结果的准确性和弱阳性标本的检出率。     

联合应用mTI-ASL和IVIM技术在鉴别高级别胶质瘤术后复发与假性进展中的应用价值

目的: 探讨应用多反转时间动脉自旋标记(multiple inversion time-pulsed arterial spin labeling,mTI-ASL)和体素内不相干运动(intravoxel incoherent motion,IVIM)技术在脑胶质瘤术后复发与假性进展中的鉴别价值。方法: 选择2018年01月至2020年01月就诊于我院高级别胶质瘤术后放化疗后首次复查常规MR增强扫描出现异常强化的患者,行mTI-ASL及IVIM序列扫描,将获取图像数据资料进行相关后处理分析,分别手动勾画感兴趣区,测量术后异常强化区各项定量参数,即真性扩散系数(true diffusion coefficient,D)、假性扩散系数(pseudo-diffusion coefficient,D*)及灌注分数(perfusion fraction,f)、脑血流量(cerebral blood flow,CBF)和动脉通过时间(arterial transit time,ATT)。分别采用独立样本t检验比较两组感兴趣区相关参数值,从而评估mTI-ASL和IVIM技术在两者鉴别诊断中的价值。结果: (1)脑胶质瘤术后复发组CBF值(6.413±0.438)、ATT值(0.198±0.033),比假性进展组CBF值(4.654±0.372)、ATT值(0.165±0.208)高,两者比较具有统计学意义(P＜0.01)。(2)脑胶质瘤术后复发组D值(1.118±0.178),比假性进展组D值(1.380±0.236)低,两者比较具有统计学意义(P＜0.01)。(3)脑胶质瘤术后复发组D*值(17.126±4.274)、f值(0.269±0.095),比假性进展组D*值(12.755±3.974)、f值(0.169±0.052)高,两者比较具有统计学意义(P＜0.01)。结论:应用 mTI-ASL和IVIM技术有助于脑胶质瘤术后复发与假性进展的鉴别诊断。     

应用PDCA循环法提高急诊检验项目全程TAT达标率

目的应用PDCA循环法缩短急诊项目的全程结果回报时间(TAT)。方法回顾性分析2017年1-12月(PDCA循环法实施前)深圳市罗湖医院集团妇科、产科急诊项目[血常规、凝血、离子七项、血人绒毛膜促性腺激素(HCG)+孕酮]的TAT未达标率。2018年应用PDCA管理工具,绘制鱼骨图分析原因、柏拉图真因确定、甘特图制订计划,利用5W1H法制订对策,并进行对策实施。同时,购置仪器、人员培训、规范化工作流程、加强临床沟通协调。对2017年1-12月(实施前)与2018年1-6月(实施后)的急诊报告时间达标率进行比较。结果2018年1—6月,急诊项目血常规、凝血、离子七项、血HCG+孕酮申请至采样时间达标率较2017年1—12月分别上升了4.89%、4.53%、6.94%、3.63%;采样至核收时间达标率分别上升了13.33%、13.57%、37.1%、13.95%;核收至发送时间达标率分别上升了20.85%、5.96%、5.01%、6.31%。应用PDCA前后申请至采样时间、采样至核收时间、核收至发送时间,差异均有统计学意义(χ2=11.325、19.569、5.301,P<0.001)。结论应用PDCA循环法对急诊检验项目TAT达标率进行质量改进、人员培训、标准化交接班制度制订,优化标本送检流程,标本高峰期增加运送人员,保障检测仪器的质量,进一步完善了信息系统,加强了与临床的沟通、协调,可以提高急诊项目全程TAT达标率,有效缩短结果TAT。     

角膜内皮移植术后早期玻璃酸钠对泪膜及角膜上皮细胞再生的作用

目的　研究1 g·L^-1和3 g·L^-1玻璃酸钠（hyaluronate，HA）滴眼液对角膜内皮移植术后早期泪膜及角膜上皮细胞再生的作用。方法　选择2017年9月至2018年2月在北京大学第三医院行角膜内皮移植术的患者60例（60眼），随机分成1 g·L^-1HA组和3 g·L^-1HA组，每组各30例，观察标准干眼评估问卷（SPEED）评分、结膜角膜染色评分（OSS）、泪膜破裂时间（TBUT）、角膜上皮缺损范围，进行激光共聚焦显微镜检查。比较不同时间点组间、组内各指标差异。结果　SPEED评分:各时间点两组间比较差异均无统计学意义（均为P>0.05）。组内比较:两组组内术后7 d、14 d、28 d均低于前一时间点（均为P=0.000），余相邻时间点两两比较差异均无统计学意义（均为P>0.05）。TBUT:术后7 d、14 d、28 d 3 g·L^-1HA组均显著高于1 g·L^-1HA组（均为P<0.05），而术前组间差异不显著；组内比较:1 g·L^-1 HA组后一时间点较前一时间点、3 g·L^-1HA组术后7 d较术前均显著延长(均为P<0.05)，而3 g·L^-1HA组术后14 d、28 d与前一时间点差异均无统计学意义（均为P>0.05）。 OSS评分:术前及术后1 d、3 d两组间比较差异均无统计学意义（均为P>0.05），术后7 d、14 d、28 d 3 g·L^-1HA组均显著低于1 g·L^-1HA组（均为P<0.05）；组内比较:两组术后1 d OSS评分均显著高于术前（均为P=0.000），其余时间点两组均低于前一时间点（均为P=0.000）。角膜上皮缺损范围:术后1 d 两组间比较差异均无统计学意义（均为P>0.05），术后3 d、7 d 两组间比较，以及两组组内与前一时间点比较差异均有统计学意义（均为P<0.05）。角膜基底细胞密度:术前、术后28 d两组间比较，以及1 g·L^-1HA组组内术前与术后28 d比较差异均无统计学意义（均为P>0.05），而3 g·L^-1 HA组术后28 d显著低于术前（P=0.002）。结论　HA可以有效改善角膜内皮移植术后早期泪膜状态并促进角膜上皮细胞再生，存在浓度依赖性。