Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

丹蛭降糖胶囊通过mTOR/S6K1信号通路对糖尿病肾病大鼠的干预作用研究

目的研究丹蛭降糖胶囊对糖尿病肾病大鼠的肾脏病理改变和足细胞自噬水平的影响,初步探讨其相应的作用机制。方法选取GK大鼠40只,采用醋酸脱氧皮质酮-盐皮下注射联合高脂饲料喂养诱导糖尿病肾病模型。造模成功后随机分为模型组、丹蛭降糖胶囊低剂量组[0.54 g/(kg·d)]、高剂量组[1.08 g/(kg·d)]、缬沙坦组[10 mg/(kg·d)],每组10只。另选取10只同周龄正常Wistar大鼠作为正常组。模型组和正常组给予等容积生理盐水。连续灌胃10周后检测空腹血糖(FBG)、血肌酐(SCr)、尿素氮(BUN)和尿微量蛋白(U-mAlb)。Western Blot检测肾小球p-mTOR、p-S6K1、Beclin-1、LC3和Nephrin蛋白的表达,HE染色和PAS染色后于光镜下观察肾脏病理变化,电镜下观察各组亚细胞形态结构变化。结果与正常组比较,模型组FBG、SCr、BUN、U-mAlb水平升高(P<0.01);与模型组比较,丹蛭降糖胶囊低、高剂量组和缬沙坦组U-mAlb水平降低(P<0.01)。模型组可见肾小球基底膜增厚,系膜基质沉积,足细胞损伤,各用药组均有不同程度改善,丹蛭降糖胶囊高剂量组足细胞内有较多自噬体形成。与正常组比较,模型组p-mTOR、p-S6K1的表达增高,Nephrin、Beclin-1和LC3的表达水平降低(P<0.01);与模型组比较,各用药组p-mTOR、p-S6K1的表达下降,Nephrin、Beclin-1和LC3的表达增高(P<0.01)。丹蛭降糖胶囊高剂量组和缬沙坦组Beclin1、LC3Ⅱ/LC3Ⅰ水平较丹蛭降糖胶囊低剂量组升高(P<0.05)。结论丹蛭降糖胶囊具有减轻糖尿病肾病大鼠U-mAIb、足细胞损伤及相关肾脏病理改变的作用,其机制可能与抑制mTOR/S6K1信号通路进而提高足细胞的自噬活性有关。     

针刺配合肠炎散保留灌肠治疗肛窦炎临床研究

目的观察肛窦炎应用针刺配合肠炎散保留灌肠治疗的效果。方法选取2017年10月-2018年10月就诊的72例肛窦炎患者,采用随机数字表法分为观察组(n=36)与对照组(n=36)。对照组给予肠炎散保留灌肠治疗,观察组为针刺配合肠炎散保留灌肠治疗,比较2组症状、疗效及安全性。结果观察组症状(放射痛、指诊症状及镜检症状)少于对照组,总有效率高于对照组,差异有统计学意义(P<0.05);2组安全性相比,差异无统计学意义(P>0.05)。结论针对肛窦炎患者,予以针刺配合肠炎散保留灌肠治疗效果确切,可减少临床症状,加快疾病转归,且治疗安全性较好。     

Revisiting the Hydrogen Storage Behavior of the Na-O-H System

Solid-state reactions between sodium hydride and sodium hydroxide are unusual among hydride-hydroxide systems since hydrogen can be stored reversibly. In order to understand the relationship between hydrogen uptake/release properties and phase/structure evolution, the dehydrogenation and hydrogenation behavior of the Na-O-H system has been investigated in detail both ex- and in-situ. Simultaneous thermogravimetric-differential thermal analysis coupled to mass spectrometry (TG-DTA-MS) experiments of NaH-NaOH composites reveal two principal features: Firstly, an H₂ desorption event occurring between 240 and 380 °C and secondly an additional endothermic process at around 170 °C with no associated weight change. In-situ high-resolution synchrotron powder X-ray diffraction showed that NaOH appears to form a solid solution with NaH yielding a new cubic complex hydride phase below 200 °C. The Na-H-OH phase persists up to the maximum temperature of the in-situ diffraction experiment shortly before dehydrogenation occurs. The present work suggests that not only is the inter-phase synergic interaction of protic hydrogen (in NaOH) and hydridic hydrogen (in NaH) important in the dehydrogenation mechanism, but that also an intra-phase H^δ+… H^δ– interaction may be a crucial step in the desorption process.     

补脾泻肝法治疗腹泻型肠易激综合征临床研究

目的观察补脾泻肝法治疗腹泻型肠易激综合征的临床疗效。方法100例腹泻型肠易激综合征患者随机分为2组,治疗组60例给予白术芍药散加味,对照组40例给予丙咪嗪合替加色罗治疗。2组均4周为1个疗程,观察疗效,并于3-6个月后观察2组病例复发情况。结果治疗组治愈率为65%,总有效率为85%,6个月内复发率为20%,对照组则分别为32.5%、72.5%、55.56%,2组比较差异均有统计学意义(均P<0.05)。结论补脾泻肝法治疗腹泻型肠易激综合征优于丙咪嗪合替加色罗,疗效确切。     

仙人掌粉对糖尿病大鼠血糖的影响

目的　研究仙人掌对糖尿病血糖的影响。方法　采用四氧嘧啶造成大鼠实验性糖尿病模型 ,然后将高、中、低 3种剂量的仙人掌粉加入到基础饲料中进行实验观察。结果　仙人掌粉高 (10g kg·d)、中 (5 .0g kg·d)剂量组均可显著降低糖尿病大鼠空腹血糖 ,并且高剂量组具有显著改善糖尿病大鼠尿量增加的作用。各剂量组对正常大鼠血糖无明显影响。结论　仙人掌粉能有效降低四氧嘧啶所导致的糖尿病大鼠的血糖、尿量     

无名异冲剂促进去卵巢大鼠骨质疏松性骨折愈合的机制研究

为探讨无名异冲剂促进去卵巢 SD大鼠骨质疏松性骨折愈合的机制 ,用 48只 6月龄雄性 SD大鼠建立骨质疏松性骨折模型 ,随机分为模型组、跳骨片组、仙灵骨葆组、无名异冲剂组 ,于灌胃后 2周、4周取材 ,观察 X线片、骨密度、光镜 ,骨痂钙、磷、胶原含量 ,结果显示灌胃第 2周时 ,各组动物各项指标均无显著性差异 ;第4周时 ,无名异冲剂组的骨密度 ,骨痂钙、磷、胶原含量的检测结果与模型组有显著性差异 ( P<0 .0 5 ) ,X线及光镜观察骨痂的生长情况 ,无名异冲剂组也优于模型组 ,说明无名异冲剂能够通过提高骨密度 ,改善骨骼钙、磷、胶原的代谢 ,促进骨折端骨痂的生长 ,达到治疗骨质疏松性骨折的目的。     

Simultaneous Quantification of an Enantiomer and the Racemic Compound of Ibuprofen by X-ray Powder Diffractometry

Purpose. An X-ray powder diffractometric method was developed for the simultaneous quantification of the relative amounts of the racemic compound (±) of ibuprofen (I) and S(+)-ibuprofen (II), when they occur as a mixture. Methods. The X-ray powder diffraction patterns of I and II show pronounced differences. This formed the basis for the determination of the relative amounts of I and II when they occur as a mixture. X-ray lines with d-spacings of 14.41 and 4.37 Å were unique to I and II, respectively. Mixtures containing different proportions of I and II were prepared which also contained lithium fluoride (III) as an internal standard. Results. A linear relationship was obtained when the intensity ratio (intensity of the 4.37 Å line of II/intensity of the 2.01 Å line of III) was plotted as a function of the weight fraction of II in the mixture. Similar results were obtained in the case of I. Using these standard curves, the weight fractions of I and II in 'unknown' mixtures were determined. The experimentally determined analyte concentration ranged between 98 and 104% of the true value. The relative error in the analyses of individual samples was < 10%. The minimum detectable weight fraction of I in II and II in I were 0.032 (3.2% w/w) and 0.034 (3.4% w/w), respectively. The minimum quantifiable weight fractions were 0.136 for I and 0.112 for II. Since the X-ray diffraction patterns of S(+)-ibuprofen and R(–)-ibuprofen are identical, the conclusions drawn regarding mixtures of I and II will also hold true in the quantitative analyses of mixtures of I and R(–)-ibuprofen.     

强化婴幼儿奶粉中叶酸的测定

强化叶酸的奶粉在0.05M K_2HPO_4缓冲液中,经均质,调pH4.5,15000g离心20分钟,其清液调pH4.0,进行CGS树脂离子交换层析,用10ml KClK_2HPO_4洗脱,调pH7.0,进行HPLC测定,采用300x3.9mm ODS反相柱,移动相0.05M K_2HPO+MeOH(91+9),流速1ml/分,紫外检测器波长285nm,灵敏度0.0050D。方法相对标准偏差为±3.3％,回收率为87％,最小检测量为0.02μg/ml。