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41.
S. Stegemann F. Leveiller D. Franchi H. de Jong H. Lindn 《European journal of pharmaceutical sciences》2007,31(5):249-261
Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.
The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail. 相似文献
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The present study was designed to investigate the effects of combined treatment with a serotonin (5-HT)1A receptor agonist, 8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT), and a muscarinic acetylcholine receptor antagonist, scopolamine, on water maze (WM) navigation. Treatment with either 8-OH-DPAT or scopolamine before daily behavioral training disrupted spatial navigation at medium doses and cue navigation at high doses. Pretraining treatment with a combination of subthreshold doses of 8-OH-DPAT and scopolamine impaired WM spatial and cue navigation, but did not impair the WM performance if the drugs were injected post-training. In trained rats, combined injections of subthreshold doses of 8-OH-DPAT and scopolamine given pretraining did not impair the rats' ability to find the platform in a familiar or in a novel position. The combination of 8-OH-DPAT and scopolamine also disrupted WM navigation in rats with central 5-HT depletion. A combination of a peripheral muscarinic acetylcholine receptor antagonist and 8-OH-DPAT had no effect on WM navigation. These data suggest that combined treatment with drugs blocking muscarinic acetylcholine receptors and activating 5-HT1A receptors greatly impairs WM learning/performance, but does not impair spatial memory per se. 相似文献
44.
施地瑞玛生理性海水鼻腔喷雾器治疗小儿干燥性鼻炎的临床观察 总被引:1,自引:0,他引:1
目的:探讨施地瑞玛生理性海水鼻腔喷雾器治疗小儿干燥性鼻炎的疗效。方法:将58例患儿随机分成2组,2组均不使用其他药物。治疗组给予施地瑞玛生理性海水鼻腔喷雾器喷鼻;对照组给予生理性盐水滴鼻液滴鼻,观察2组治疗前后症状、体征及有效率。结果:根据2组的主要症状、体征及疗效,治疗组优于对照组(P<0.05)。结论:生理性海水鼻腔喷雾器治疗小儿干燥性鼻炎,可以缩短病程,改善鼻腔功能,疗效确切,且使用安全、舒适、方便,可以作为治疗小儿干燥性鼻炎的理想药物。 相似文献
45.
Zheng-Hua ZHU Bai-Ren WANG Qing-Rong TAN Xiao-Li DUAN Fang KUANG Zhen XU Gong JU Institute of Neurosciences Department of Psychiatrics the Fourth Military Medical University X i’an China 《中国神经科学杂志》2006,(3)
1 Introduction Exposure to hostile stressors causes a series of coor- dinated responses in the body, such as alterations of neu- roendocrine secretion, immune reaction and behavioral manifestation to maintain homeostasis stability and sur-vival of the organisms. Stressors are divided into two main categories: physical, or systemic, and psychological, or emotional / processive. Each stressor might activate a spe- cific central pathway to induce a special neuroendocrine response, even cause stre… 相似文献
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目的:评价口服水剂、水灌肠及两者联合应用充盈肠道后,使用MSCT显示成人正常肠道的能力。材料和方法:将43名非肠道病变志愿者分别采用口服水剂法(21例)、水灌肠法(12例)、双重法(口服水剂和水灌肠联合应用,10例)充盈肠道,然后行MSCT平扫和增强扫描并进行图像重建,对小肠和大肠各肠段充盈状态进行评价。结果:口服水剂法回肠充盈良好,水灌肠法大肠充盈良好,双重法回肠及大肠均充盈良好。口服水剂法小肠充盈优于水灌肠法,与双重法无显著差异,大肠充盈状态水灌肠法明显优于口服水剂法,与双重法无显著差异。结论:口服水剂和水灌肠联合应用可以在MSCT同时较好地充盈显示小肠和大肠,而两种方法单独使用则仅能分别充盈显示小肠和大肠,需要根据显示目的选择相应的充盈方法。 相似文献
48.
Ivar Rønnestad Einar Thorsen Kåre Segadal Arvid Hope 《European journal of applied physiology》1994,69(1):32-35
In diving, pulmonary mechanical function is limited by the increased density of the gas breathed. Breathing cold and dry gas may cause an additional increase in airways resistance. We have measured forced vital capacity, forced expired volume in 1 s (FEV1) and forced midexpiratory flow rate (FEF25%–75%) before and after breathing dry or humid gas at 29–32°C during a standardized exercise intensity on a cycle ergometer at an ambient pressure of 3.7 MPa. The atmosphere was a helium and oxygen mixture with a density of 6.8 kg · m–3. Six professional saturation divers aged 26–37 years participated in the study. There were no significant differences in convective respiratory heat loss between the exposures. The mean evaporative heat loss was 67 W (range 59–89) breathing dry gas and 37 W (range 32–43) breathing humid gas, corresponding to water losses of 1.7 g · min–1 (range 1.5–2.2) and 0.9 g · min–1 (range 0.8–1.1), respectively. There was a significant reduction in FEV1 of 4.6 (SD 3.6)% (P<0.05), and in FEF25%–75% of 5.8 (SD 4.7)% (P<0.05) after breathing dry gas. There were no changes after breathing humid gas. By warming and humidifying the gas breathed in deep saturation diving bronchoconstriction may be prevented. 相似文献
49.
Zhiqiang Li Arthur F Gmitro Ali Bilgin Maria I Altbach 《Magnetic resonance in medicine》2007,57(6):1047-1057
Three-point Dixon techniques achieve good lipid-water separation by estimating the phase due to field inhomogeneities. Recently it was demonstrated that the combination of an iterative algorithm (iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL)) with a fast spin-echo (FSE) three-point Dixon method yielded robust lipid-water decomposition. As an alternative to FSE, the gradient- and spin-echo (GRASE) technique has been developed for efficient data collection. In this work we present a method for lipid-water separation by combining IDEAL with the GRASE technique. An approach to correct for errors in the lipid-water decomposition caused by phase distortions due to the switching of the readout gradient polarities inherent to GRASE is presented. The IDEAL-GRASE technique is demonstrated in phantoms and in vivo for various applications, including pelvic, musculoskeletal, and (breath-hold) cardiac imaging. 相似文献
50.
2006年新疆且末县饮水氟砷及地方性氟中毒调查报告 总被引:1,自引:0,他引:1
目的 了解新疆且末县生活饮用水氟、砷含量及地方性氟中毒(下简称地氟)病情. 方法 2006年5~9月对且末县30个行政村饮用水氟含量和15个行政村水砷含量进行了筛查,对20个行政村降氟、降砷改水工程使用情况进行了调查及水氟、水砷含量检测;地方性氟中毒病情检查3 164人,其中8~12岁学生检查1 242人,成人检查1 922人.结果 且末县56.3%地下水水氟含量偏高,水砷不高,儿童氟斑牙率40.41%. 结论 新疆且末县尚有部分居民患地氟病,应引起重视. 相似文献