盐酸川芎嗪在冷冻干燥工艺中的稳定性研究

目的 对盐酸川芎嗪在冻干制备工艺中的稳定性进行考察,为保障含有该成分的其他冻干粉针剂产品的质量提供依据。方法 采用HPLC法测定盐酸川芎嗪的量。色谱条件：流动相为甲醇-水（45：55）,体积流量为1.0 mL/min,柱温25℃,进样量10 μL,检测波长为295 nm。检测盐酸川芎嗪在升华干燥0、12、24、48 h后的含量变化。结果 盐酸川芎嗪在10.5~168 μg/mL内呈良好的线性关系,回归方程为Y=25.837X+10.669（R²=1）。此方法检测盐酸川芎嗪在升华干燥12 h后含量减少9%,24 h其含量减少40%以上,48 h几乎完全损失。结论 盐酸川芎嗪在冷冻干燥过程中随时间延长会因升华而使含量损失加重。     

星点设计-响应面法优选菊苣叶干燥方法和炮制工艺

目的以绿原酸和菊苣酸及浸出物含量为指标,建立菊苣Cichorium intybus叶最佳干燥方法;优选菊苣叶饮片的最佳炮制工艺,为菊苣叶的开发应用奠定基础。方法建立菊苣叶中绿原酸和菊苣酸含量测定的HPLC方法,测定条件:色谱柱为Agilent Zorbax Eclipse XDB-C18柱(250 mm×4.6 mm,5μm),以乙腈-0.4%磷酸水溶液为流动相梯度洗脱,体积流量为1 mL/min,柱温为30℃,检测波长为334 nm;采用绿原酸和菊苣酸及浸出物多指标确定菊苣叶最佳干燥方法;采用星点设计-响应面法对菊苣叶切制段长、干燥温度、干燥时间进行考察,以绿原酸、菊苣酸、浸出物含量及色度值、饮片外观性状等按照权重计分为评价指标并进行综合分析。结果菊苣叶最佳干燥方法为远红外干燥法;菊苣叶饮片炮制工艺条件为切制段长7 mm、干燥温度为50℃、干燥时间为17 h。结论优选出的菊苣叶炮制工艺综合评分较高,不仅最大限度保留有效成分,而且饮片色泽好,可重复性强,工艺稳定可靠。     

氧驱动雾化吸入器消毒方法的临床研究

目的调查临床使用雾化吸入器沾染的细菌种类和3种不同处理方法的灭菌效果。方法通过细菌培养法鉴定雾化吸入器的细菌污染情况,分别采用清水冲洗、酒精擦洗和健之素浸泡的方法进行处理后再次进行细菌培养。结果临床使用的雾化吸入器上含有致病细菌,清水冲洗酒精擦洗和健之素浸泡能清除雾化器表面的多数细菌,细菌清除率为73.80%、81.59%和93.42%,只有健之素组符合国家标准。结论健之素浸泡是临床消毒雾化吸入器的简便有效方法。     

利多卡因超声雾化吸入用于扁桃体术后的镇痛效果分析

目的探讨利多卡因超声雾化吸入用于扁桃体摘除手术后患者的镇痛效果.方法: 将扁桃体摘除手术患者65例随机分成两组,观察组33例,对照组32例,分别给予0.5%的利多卡因超声雾化和0.9% NS超声雾化治疗.结果: 观察组疼痛明显减轻,术后首次进食时间提前,24h睡眠质量提高,咽部异物感减轻(P<0.01).结论: 扁桃体术后利多卡因超声雾化吸入是一种安全、有效、简便、无创的镇痛方法.     

不同干燥方法对丹参毛状根有效成分含量及其抗氧化活性的影响

目的：探讨不同干燥方法对丹参毛状根中主要化学成分含量及其抗氧化活性的影响,尤其关注采后干燥对丹参毛状根酚酸类成分是否也有类似对植物根一样的胁迫诱导作用。方法丹参毛状根经冷冻干燥、真空干燥、阴干和晒干四种不同干燥方式处理后,采用高效液相色谱法测定毛状根中包括9种酚酸类和4种酮类成分的含量;利用1,1-二苯基-2-三硝基苯肼（ DPPH）自由基清除试验、超氧阴离子清除试验、脂质过氧化抑制试验测定毛状根提取物的抗氧化活性。结果与冷冻干燥相比,真空干燥和阴干对酚酸类成分的影响不大,但酮类成分下降约50％;晒干处理后二类成分均严重损失达90％左右;晒干样品提取物抗氧化活性也显著下降。结论冷冻干燥是最适合丹参毛状根的干燥方法;与丹参根不同,采后干燥对毛状根的酚酸类成分无诱导作用。     

Optimization of secondary drying condition for desired residual water content in a lyophilized product using a novel simulation program for pharmaceutical lyophilization

The aim of this study was to optimize the shelf temperature and the drying time, mainly dependent on the residual water content of a lyophilized product using a novel simulation program for the secondary drying of lyophilization. The simulation program was developed based upon heat transfer formulas, two empirical formulas, and a modified Fick’s second law. When a preliminary lyophilization run of secondary drying was carried out, the equilibrium product temperature at the end of secondary drying under various shelf temperatures was accurately predicted by the heat transfer formulas. The apparent diffusion coefficient of water, D_eff, and the apparent equilibrium residual water content, W_e, under the predicted equilibrium product temperature were estimated by two empirical formulas. These estimated D_eff and W_e allow the modified Fick’s second law to predict the residual water content in the lyophilized product. Using the developed simulation program, it was verified that the secondary drying condition to achieve the desired residual water content in the lyophilized product was successfully predicted. Therefore, the simulation program can be used to effectively design the secondary drying condition of lyophilization cycles without a trial and error approach.     

Influence of the spray adjuvant on the toxicity effects of a glyphosate formulation

In the present study, the influence of the spray adjuvant on the toxicity effects of a glyphosate formulation was examined in HEp-2 cell line. We determined the median lethal concentration (LC₅₀) of Atanor® (glyphosate formulation), Impacto® (spray adjuvant) and the mixture of both agrochemicals. We also compared the toxicities of the pesticides individually and in mixture and we analyzed the effects on oxidative balance from each treatment.Our results showed that all the agrochemicals assayed induce dose and time-dependent cytotoxicity and that the toxicity of Impacto® with Atanor® (mixture) was additive on HEp-2 cell line.All the agrochemicals assayed produced an increase in catalase activity and glutathione levels, while no effects were observed for superoxide dismutase and glutathione-S-transferase activities. We found an important increase in ROS production in cells treated with Atanor® and mixture. Besides, all the agrochemicals used triggered caspase 3/7 activation and hence induced apoptosis pathway in this cell line. In conclusion, our results demonstrated that the addition of adjuvant to glyphosate formulation increase the toxicity of the mixture in cell culture. Furthermore, cell culture exposed to agrochemical mixture showed an increased ROS production and antioxidant defenses.     

重组人干扰素α2b喷雾剂治疗手足口病的疗效观察

目的：评价重组人干扰素α2b喷雾剂治疗手足口病的临床疗效。方法收治手足口病患儿174例,随机分为治疗组88例和对照组86例。两组均给予热毒宁注射液、利巴韦林静滴治疗。治疗组在对照组的基础上增加重组人干扰素α2b喷雾剂局部治疗。比较两组在发热消退时间、口腔疱疹消退时间、手足臀部疱疹消退时间及总病程等方面的变化和差异。结果治疗组发热消退时间、口腔疱疹消退时间、手足臀部疱疹消退时间及总病程等均较对照组明显缩短,差异有统计学意义（P〈0.05）。结论重组人干扰素α2b喷雾剂治疗手足口病疗效显著,临床无明显不良反应。     

Fabrication of a Novel Protein Sponge with Dual-Scale Porosity and Mixed Wettability Using a Clean and Versatile Microwave-Based Process

An open-porous protein sponge with mixed wettability is presented made entirely from whey proteins and with promising applications in biomedicine, pharmaceutical, and food industry. The fabrication relies on an additive-free, clean and scalable process consisting of foaming followed by controlled microwave-convection drying. Volumetric heating throughout the matrix induced by microwaves causes fast expansion and elongation of the foam bubbles, retards crust formation and promotes early protein denaturation. These effects counteract collapse and shrinkage typically encountered in convection drying of foams. The interplay of high protein content, tailored gas incorporation and controlled drying result in a dried structure with dual-scale porosity composed of open macroscopic elongated foam bubbles and microscopic pores in the surrounding solid lamellae induced by water evaporation. Due to the insolubility and mixed wettability of the denatured protein network, polar and non-polar liquids are rapidly absorbed into the interconnected capillary system of the sponge without disintegrating. While non-watery liquids penetrate the pores by capillary suction, water diffuses also into the stiff protein matrix, inducing swelling and softening. Consequently, the water-filled soft sponge can be emptied by compression and re-absorbs any wetting liquid into the free capillary space.     

Lyophilization Process Design and Development: A Single-Step Drying Approach

High-throughput lyophilization process was designed and developed for protein formulations using a single-step drying approach at a shelf temperature (T_s) of ≥40°C. Model proteins were evaluated at different protein concentrations in amorphous-only and amorphous-crystalline formulations. Single-step drying resulted in product temperature (T_p) above the collapse temperature (T_c) and a significant reduction (of at least 40%) in process time compared to the control cycle (wherein T_p < T_c). For the amorphous-only formulation at a protein concentration of ≤25 mg/mL, single-step drying resulted in product shrinkage and partial collapse, whereas a 50 mg/mL concentration showed minor product shrinkage. The presence of a crystallizing bulking agent improved product appearance at ≤25 mg/mL protein concentration for single-step drying. No impact to other product quality attributes was observed for single-step drying. Vial type, fill height, and scale-up considerations (i.e., choked flow, condenser capacity, lyophilizer design and geometry) were the important factors identified for successful implementation of single-step drying. Although single-step drying showed significant reduction in the edge vial effect, the scale-up considerations need to be addressed critically. Finally, the single-step drying approach can indeed make the lyophilization process high throughput compared to traditional freeze-drying process (i.e., 2-step drying).