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该文归纳出中药"显效理论",即中药通过"众多显效形式(显效型)的单靶点叠加作用、多靶点协同作用及毒性分散效应"发挥药效并削弱自身毒性。一味中药可含有约1 000种成分,一种成分口服进入体内后又可产生约100种代谢产物。无数化学成分及其无数体内代谢产物中的众多显效形式可共同发挥"集团军式作用"。在药物分子少、靶点分子多的情况下,中药不同种的显效型分子可相继与靶点分子结合,发生叠加作用,当"靶点充分占位"时药效始启动。既有浓度上的叠加作用又有时间段先后的叠加作用,这使得药效得以持久。显效型呈现药效叠加和毒性分散,源于不同显效形式分子结构之间药效基团相同而毒性基团不完全相同。"毒性分散效应"适于对无毒中药而不适于对有毒中药的解释。显效理论揭示中药可以众多化学成分及众多代谢产物参与发挥药效过程,包括叠加作用、协同作用及毒性分散效应,可有助于阐释和弘扬中药特色优势。今后需研究/确证的问题:中药药效物质基础及其作用机制是怎样构成的?多数中药为什么毒性小?体现中药特色优势的中药"显效理论"如何在新药研发中应用? 相似文献
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【目的】基于拉曼光谱技术,探讨肉苁蓉苯乙醇苷对Fenton’s试剂诱导人精子氧化损伤的保护作用。【方法】体外建立氧化损伤精子模型,给予肉苁蓉苯乙醇苷(剂量分别为0.1、0.01、0.001μg/mL)保护处理后,采用共聚焦显微拉曼光谱技术,检测分析精子核部DNA的变化情况。【结果】 Fenton’s试剂致使人精子细胞核拉曼光谱的强度和峰位移发生显著变化,给予肉苁蓉苯乙醇苷保护处理后,这种变化被抑制,且呈一定的剂量相关性。【结论】肉苁蓉苯乙醇苷对氧化损伤人精子DNA具有一定的保护作用。 相似文献
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病原微生物检测一直是微生物学研究领域的热点,常规检测方法,如分离培养、PCR、ELISA和基因组测序等,样品前处理复杂,耗时较长,不利于现场和实时在线检测。光谱技术因具有快速准确、安全高效、非破坏性和便于在线侦检等特点,成为一种新型无创检测技术,在病原微生物检测、疾病诊断等领域得到迅速发展。该文就3种常用的光谱技术,即激光激发荧光光谱、红外光谱和拉曼光谱在病原微生物检测中的工作原理、研究进展作一综述,讨论各自优缺点,并展望其应用前景。 相似文献
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Y. Yoshioka E. Yamachika M. Nakanishi T. Ninomiya K. Nakatsuji Y. Kobayashi T. Fujii S. Iida 《The British journal of oral & maxillofacial surgery》2018,56(8):732-738
Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO32?) in its crystal structure. 相似文献
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Ashwinkumar A. Bhirde Meng-Jung Chiang Ramesh Venna Serge Beaucage Kurt Brorson 《Journal of pharmaceutical sciences》2018,107(8):2055-2062
Stability of therapeutic proteins (TPs) is a critical quality attribute that impacts both safety and efficacy of the drug. Size stability is routinely performed during and after biomanufacturing. Dynamic light scattering (DLS) is a commonly used technique to characterize hydrodynamic size of the TPs. Herein, we have developed a novel method to evaluate in-use and thermal stress stability of TPs using algorithm-driven high-throughput DLS. Five marketed TPs were tested under the guidance of customized algorithms. The TPs were evaluated at relevant temperature conditions as well as under dilution and thermal stress for size stability. We found that the TPs were stable under the in-use conditions tested; however, sample loss due to evaporation can lead to large protein aggregates. A combined assessment of autocorrelation function and photos of sample well could be useful in formulation screening. Dilution of TPs also has an impact on the hydrodynamic size. Thermal stress experiments showed the importance of using different data processing methods to access size distribution. Polydispersity index was useful in evaluating sample heterogeneity. Herein, we show that algorithm-driven high-throughput DLS can provide additional supportive information during and after biomanufacturing and the potential to be used in a quality control environment. 相似文献
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Hristo Svilenov Lorenzo Gentiluomo Wolfgang Friess Dierk Roessner Gerhard Winter 《Journal of pharmaceutical sciences》2018,107(12):3007-3013
The early-stage assessment of the physical stability of new monoclonal antibodies in different formulations is often based on high-throughput techniques that suffer from various drawbacks. Accordingly, new approaches that facilitate the protein formulation development can be of high value to the industry. In this study, a dynamic light scattering plate reader is used to measure the aggregation (by means of the increase in the hydrodynamic radius [Rh]) of monoclonal antibody samples that were subject to incubation and subsequent dilution from different concentrations of a denaturing agent, that is, guanidine hydrochloride. The increase in the Rh of the protein samples is dependent not only on the denaturant concentration used but also on the buffer in which the incubation/dilution was performed. We also compare the aggregation after dilution from a denaturant with other high-throughput stability-indicating methods and find good agreement between the techniques. The proposed approach to probe the physical stability of monoclonal antibodies in different formulation conditions offers a unique combination of features—it is isothermal, probes both the resistance to denaturant-induced unfolding and the colloidal protein stability, it is entirely label-free, does not rely on complex data evaluation, and requires very short instrument measurement time on standard equipment. 相似文献