星点设计-效应面法优化姜黄素牛血清白蛋白纳米粒的制备工艺

摘 要 目的：星点设计 效应面法优化姜黄素牛血清白蛋白纳米粒(CUR BSA NPs)的制备工艺,考察其外观粒径分布及体外释放特性。 方法: 以牛血清白蛋白为载体材料,姜黄素作为模型药物,采用去溶剂法制备CUR BSA NPs,通过星点设计 效应面法优化其制备工艺,并对CUR BSA NPs的外观形态、粒径分布、包封率、载药量及体外释放进行研究。 结果: CUR BSA NPs制备的最佳工艺条件为牛血清白蛋白浓度10 mg·ml-1,乙醇体积7.79 ml,搅拌速度915 r·min-1。根据优化处方工艺制备的CUR BSA NPs外观呈圆形或类圆形,平均粒径（203.93±83.10） nm,Zeta电位-40～-50 mV;包封率为86.53%,载药量为3.89%。 结论: 最优工艺条件下制备的CUR BSA NPs包封率和载药量高,粒径分布较为均匀,体外释放试验表明与姜黄素原料药相比制备的CUR BSA NPs有良好的缓释特性。     

Transapical mitral valved stent implantation: Enhanced survival and decreased paravalvular leakages

Background/Objectives

This study presents the recent results of transapical implantation of a new design of a mitral valved stent with up to three months follow-up.

Methods

A self-expanding re-designed mitral valved stent was implanted via transapical approach into the beating heart of eight pigs. Echocardiographic- and hemodynamic parameters were assessed before (n = 8), at 1 h (n = 8), at one month (n = 6), at two months (n = 2), and at three months (n = 1) after implantation and a cardiac CT was conducted.

Results

The stent was successfully deployed in all animals. Two animals died within the first month due to incorrect fixation force. Echocardiographic evaluation showed low gradients (3.9 ± 1.4 mm Hg and 1.9 ± 0.8 mm Hg across the valved stent and aortic valve) and a normal mitral annular plane systolic excursion (1.1 ± 0.2 cm) after one month. No paravalvular leakages (PVL) were detected after 1 h. The pulmonary artery pressure did not increase after valved stent implantation (p ≥ 0.106). The pulmonary capillary wedge pressure (PCWP) slightly increased to 16 ± 3 mm Hg after one month (p = 0.033). The left ventricular end-diastolic pressure was mildly elevated (15.8 ± 8.6 mm Hg) after one month.

Conclusions

Secure deployment and correct position of the valved stents were reproducibly achieved in the off-pump implantation procedure. No paravalvular leakages after 1 h as well as low gradients, few stent fractures and a normal longitudinal function after one month were achieved with this newly developed and well-aligned prototype. However, a number of challenges have been identified during this study and potential for improvement has been identified.     

Treatment Retention Satisfaction,and Therapeutic Progress for Justice-Involved Individuals Referred to Community-Based Medication-Assisted Treatment

Background: Limited research has examined factors associated with medication-assisted treatment for justice-involved individuals. Objectives: The current study used a mixed-method design to examine the influence of client- and counselor-level factors on 90-day treatment retention, satisfaction, and progress for justice-involved individuals referred to medication-assisted treatment. Methods: The effects of co-occurring disorders (i.e., psychiatric symptoms, anxiety, depression), social functioning (i.e., social support, self-esteem), substance use severity, and treatment motivation on treatment retention, treatment satisfaction, and treatment progress while controlling for counselor-level variance were assessed through multilevel modeling. Results: Fewer co-occurring disorders and more social support were related to greater treatment satisfaction and progress. A higher level of treatment motivation was associated with greater treatment progress. Mediation of treatment satisfaction on the relationship between client-level factors and treatment progress also was tested. Depression was negatively associated with treatment satisfaction, which in turn led to lower ratings of treatment progress. Social support was positively correlated with treatment satisfaction, which in turn was positively correlated with treatment progress. The association of client substance use severity with treatment retention differed between counselors, so did the association of co-occurring disorders and treatment motivation with treatment satisfaction. Qualitative analyses that were derived from counselors’ perception of factors relating to recovery success underscored the importance of integrated interventions, social support, treatment motivation, and therapeutic alliance, and their associations with treatment outcomes. Conclusions/Importance: The current findings highlight the importance of integrated treatment services, collaborating with community corrections, and teaching clients strategies for dealing with deviant peers as to facilitating recovery.     

Formulation of sustained release bioadhesive minitablets containing solid dispersion of levofloxacin for once daily ocular use

This study aimed to increase ocular residence time of levofloxacin by formulation into zero-order sustained release mucoadhesive minitablets for once daily administration using a hydrophobic–hydrophilic polymeric matrix. Levofloxacin was first formulated into solid dispersion with different ratios of Eudragit^® RS then the resulting solid dispersion was mixed with different concentrations of Carbopol^® and other excipients to be finally compressed into minitablets. A 2⁴ full factorial design was employed to estimate the effects and interactions of two formulation factors, and to establish their relationships with selected responses in the developed minitablets. The studied factors were: drug to Eudragit^® RS ratio, and percent of Carbopol^® in the minitablets. Sixteen ocular minitablets formulations were prepared and evaluated for the cumulative percentages drug release at 6, 12, and 24?h, as well as mucoadhesion time, mucoadhesive strength, and swelling index as response variables. After optimizing the responses, the optimized formulation was found to be stable on sterilization using gamma-irradiation and storage at 40?°C/75% RH for six months. In vivo testing of the optimized formulation showed that the minitablets extended levofloxacin release up to 24?h without causing any ocular irritation. The optimized formulation exhibited superior microbiological activity compared to the commercial product.     

基于精益管理理论的出院带药流程再造实践与体会

目的 运用精益管理（lean management,LM）理论,对出院带药进行流程再造。方法 通过使用价值流图（Value Stream Mapping）和7种浪费（Seven Wastes）2种LM工具对原出院带药流程进行分析,通过多部门协作对流程进行再造。结果 新流程的实施减少了出院带药流通环节,降低出错机率,保证了患者用药安全;减轻了医护人员的工作强度,减少了人力资源成本,缩短了患者的出院时间,提高了患者和医务人员的满意度,并让患者享受到药师专业的用药指导服务。结论 新流程提供了高品质、方便快捷的出院带药服务,保证了患者用药安全。     

响应面法优化乌蔹莓的提取工艺

目的：利用Box-Behnken响应面法优化乌蔹莓软膏原料的最佳醇提工艺。方法：以干浸膏得率和木犀草素含量作为评价指标,通过响应面法优化工艺,采用综合评分法作评价指标,并进行二项式方程拟合,预测最佳工艺。结果：对指标影响最大的是醇倍量,其次为提取时间,影响最小的为乙醇浓度。最佳醇提工艺条件为：醇倍量12倍;提取时间2.5 h;乙醇浓度70%。3次验证试验的木犀草素平均含量为0.32 mg·g-1;综合得分为0.98,与预测值的相对误差为2.2%。结论：响应面法优化的提取干浸膏工艺高效稳定,木犀草素提取率较高,为乌蔹莓软膏的开发奠定了基础。     

莫匹罗星壳聚糖纳米粒原位凝胶的制备与体外抗菌活性研究

目的：制备莫匹罗星壳聚糖纳米粒（Mupirocin-loaded chitosan nanoparticles,Mup-loaded CNs）原位凝胶,并考察其体外抗菌活性。方法：采用离子凝胶化法制备Mup-loaded CNs,以药物与壳聚糖比例（X₁）、pH值（X₂）、搅拌速度（X₃）作为考察对象,以药物包封率（Y）作为评价指标,运用Box-Behnken实验设计法优化Mup-loaded CNs处方和制备工艺;采用Malvern Zetasizer Nano型激光粒度仪测定其粒径分布和Zeta电位,透射电镜观察微观形态;以泊洛沙姆407作为凝胶基质将Mup-loaded CNs制备成原位凝胶;并比较了莫匹罗星软膏、Mup-loaded CNs以及原位凝胶的体外抗菌活性。结果：优化得到Mup-loaded CNs处方组成及制备工艺为：药物与壳聚糖比例为0.2、pH值为3.5、搅拌速度为350 r·min^-1,Mup-loaded CNs的包封率为（89.5±1.8）%,平均粒径为（217.8±10.5） nm,PdI为（0.158±0.015）,Zeta电位为（24.8±1.8） mV;在透射电镜下可观察到Mup-loaded CNs呈近似呈球形或类球形分布,粒径分布较均匀;Mup-loaded CNs原位凝胶对金黄色葡萄球菌、大肠杆菌均有较好的抗菌效果。结论：Mup-loaded CNs原位凝胶处方设计合理,制备工艺简单,具有良好的物理性能和抗菌活性,有望成为Mup外用给药的一种新途径。