Investigation of Solid Dosage Form Components Interaction Using Orthogonal Techniques- Discovery of New Forms of Sodium Stearyl Fumarate

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life and performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in DP under accelerated storage conditions. Due to the complex drug product matrix (including API, polymer, fillers, super disintegrant and lubricant), it was challenging to pinpoint the component(s) responsible for the new peak. In addition to PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) and Infrared (IR) spectroscopy were employed in this investigation to understand the root cause mechanistically. Specifically, multi nuclei SSNMR (¹H, ²³Na, ¹³C) was instrumental in delineating the components of the matrix. We identified the root cause to be an acid base reaction occurring in the DP, whereby sodium ion in sodium stearyl fumarate (SSF) is replaced by proton leading to SSF form conversion. We also identified commercially available SSF to be a hydrate that can dehydrate to an anhydrous form upon heating. In general, the same techniques can be used to investigate interactions of any multi component solid dosage forms.     

SSF抗小鼠脑缺氧作用

目的：研究SSF对小鼠脑缺氧的保护作用。方法：10、100、200mg/kg的SSF连续ig小鼠14d，各组小鼠分别ip KCN(10mg/kg）或结扎带米走神经的双侧颈总动脉，记录小鼠ip KCN和结扎带迷走神经双侧颈总动脉后存活时间，脑复康为对照药。结果：50、100、200mg/kg SSF组小鼠ip KCN后存活时间比盐水对照组分别延长37.65%、95.67%和38.55%；100mg/kg SSF作用优于脑复康（200mg/kg）。3个剂量组小鼠结扎双侧颈总动脉存活时间分别是盐水对照组的1.84、1.94、2.29倍；100mg/kg SSF作用与200mg/kg脑复康作用相当。结论：SSF对小鼠脑缺氧有保护作用。     

Preparation of sulfonated silk fibroin for anti-coagulation material

Abstracts

Here we report the anticoagulant property of Sulfonated Silk Fibroin (SSF) which was improved by sulfonation method. Chlorosulfonic acid was applied to modify the Silk Fibroin (SF) anticoagulant property by the preparation of the SSF. The SSF was prepared in the new technology that 50?°C, 0.2?g SF/ml chlorosulfonic acid and 15?h were optimized with the reaction temperature, special concentration ratio of the SF to the chlorosulfonic acid and the certain reaction time, respectively. Then the SF reaction solution was dialyzed, and freeze-dried to form the SSF. The different properties of the SF and the SSF have been revealed by Fourier Transform Infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X-ray Photoelectron Spectrometer (XPS), Gel Permeation Chromatography (GPC), X-ray Diffraction (XRD), Activated Partial Thromboplastin Time (APTT) etc. That the sulfonic acid groups were successfully induced into the SF molecular chains has also been verified. The SSF possessed the excellent performance on the APTT value, and it can be slowly released from the Poly(epsilon-caprolactone) (PCL) composite film. In conclusion, the SSF is the novel product modified by the chlorosulfonic acid directly, and it possesses the good anti-coagulation, resulting in that it can become one of candidates of anti-coagulation materials.     

SSF改善小鼠化学性记忆障碍的作用观察

目的：研究SSF对基些化学试剂引起小鼠学习记忆障碍的作用。方法：采用小鼠水迷宫行为实验法，检测SSF对东莨菪碱、戊巴比妥钠引起小鼠学习、记忆障碍的作用。小鼠到达终点平台时间（潜伏期）和进入盲端次数作为检测指标，脑复康为对照药。结果：单次腹腔注射东莨菪碱3mg/kg明显损害已训练达标小鼠记忆，灌胃50、100、200mg/kgSSF明显逆转东莨菪碱产生小鼠记忆障碍。在连续5天记忆获得实验中，15mg/kg戊巴比妥钠明显抑制小鼠记忆获得，200mg/kg脑富康(ig,12d)和50、100、200mg/kg（灌胃，12d)SSF皆能显著降低戊巴比妥钠引起小鼠到达终点平台的潜伏期和进入盲端的次数。结论：SSF能够改善戊巴比妥钠东莨菪碱和产生的小鼠记忆障碍。     

Comparison of current methods used to detect Cryptosporidium oocysts in stools

In this review all of the methods that are currently in use for the investigation of Cryptosporidium in stool material are highlighted and critically discussed. It appears that more qualifications and background knowledge in this field regarding the diagnosis of the Cryptosporidium parasite is required. Furthermore, there is no standardization for the protocols that are commonly used to either detect oocysts in faeces or to diagnose the Cryptosporidium infection. It is therefore necessary to initiate further education and research that will assist in improving the accuracy of the diagnosis of Cryptosporidium oocysts in the faecal micro-cosmos. Where ambient concentrations of oocysts are low in stool material, detection becomes a formidable task. Procedures for ring tests and the standardization of multi-laboratory testing are recommended. It is also necessary to enhance the routine surveillance capacity of cryptosporidiosis and to improve the safety against it, considering the fact that this disease is under diagnosed and under reported. This review is intended to stimulate research that could lead to future improvements and further developments in monitoring the diagnostic methodologies that will assist in harmonizing Cryptosporidium oocysts in stool diagnosis.     

Effects of brain stem stimulation on cortical NADH fluorescence, blood flow, and O2 consumption in the cat

A causal relationship has been suggested between the altered electrical cortical activity and the increases in both cortical metabolism and blood flow which follow experimental reticulocortical activation. To further study this hypothesis, cortical O₂ consumption, NADH fluorescence, and blood flow were monitored simultaneously with aortic blood pressure and ECoG after the electrical stimulation of the pontomesencephalic reticular formation (MRF) in anesthetized cats. Reversible increases in blood pressure, cortical blood flow, and O₂ consumption, and decreases in NADH fluorescence were induced by MRF stimulation. All these changes were linearly related to each other as a function of stimulus intensity; they were often but not always associated with an increase in the ECoG frequency. MRF stimulation after ganglionic suppression with hexamethonium chloride revealed a dissociation of the resulting changes in the ECoG from the changes in cortical blood flow and metabolism. In addition, pharmacologically induced acute elevations of blood pressure caused changes in the experimental parameters similar to those which followed MRF stimulation but without a significant effect on the ECoG. We conclude that (i) acute increases in cortical blood flow and oxidative metabolism after electrical MRF stimulation may be more related to the simultaneous elevations of blood pressure than to changes in the ECoG; and (ii) an acute increase in cortical blood flow may by itself stimulate cortical oxidative metabolism in the anesthetized cat.     

一株高耐受性乳酸菌的分离及其在木质纤维素发酵生产高浓度L-乳酸中的应用

利用资源丰富的纤维质原料生产新一代可降解聚乳酸塑料的单体原料L乳酸,是目前一个极为重要的研究热点和产业方向。从高温纤维乙醇发酵介质中分离到一株高耐受性乳酸菌,经16S rDNA分子生物学鉴定为乳酸片球菌（Pediococcus acidilactici）,并命名为P. acidilactici DQ2。此菌株具有极为优异的耐高温和耐受高浓度木质纤维素降解产物的特性,这一特性可能与母株的环境变异和体系中存在的调控物质有关。利用该乳酸菌以稀酸预处理后的玉米秸秆为原料进行同步糖化与乳酸发酵,发酵液中的乳酸质量浓度为75 g/L,乳酸对纤维素得率达到0.63 g/g,具备了纤维素乳酸产业化生产的潜力。     

Activation of cat SII cortex by flutter stimulation of contralateral vs. ipsilateral forepaws

A distinguishing feature of SII cortex is that it receives substantial input from skin mechanoreceptors located on both sides of the body. It remains uncertain, however, if integration of bilateral inputs occurs mainly in those regions of SII that represent near-midline body regions or also occurs to a significant extent in those regions of SII that represent the distal extremities. This issue was addressed using extracellular microelectrode recordings in cat SII in combination with the method of optical intrinsic signal (OIS) imaging. Stimulation of the central pad of either the contra- or ipsilateral forepaw with a 25-Hz sinusoidal vertical skin displacement ("skin flutter") stimulus evoked a prominent OIS response ("activation") in an extensive anteroposterior sector of SII. In the anteriorly located SII region that yielded the maximal OIS response to stimulation of the contralateral central pad, neurons consistently possessed receptive fields that included the stimulated skin site. This "forepaw" SII region also exhibited significant although 75% weaker OIS activation in response to stimulation of the ipsilateral central pad. Stimulation of the central pads of either contra- or ipsilateral forepaws also evoked OIS activation in the posteriorly located 'hindlimb' region of SII--defined as the SII region comprised of neurons with receptive fields on the contralateral hindlimb. The OIS response to ipsilateral central pad stimulation was strongest in the posterior SII region that borders the suprasylvian fringe--a region in which neurons have very large, and frequently bilateral, cutaneous receptive fields. The results indicate that widespread regions within cat SII receive cutaneous inputs from the ipsilateral distal forelimb. It is suggested that the functional role of these ipsilateral inputs may be different in different SII regions.