目的对阿伐那非合成工艺中具有警示结构的潜在有关物质进行致突变性评价研究,为阿伐那非有关物质的分类分级提供指导和依据。方法通过化学方法定向合成阿伐那非含警示结构的潜在遗传毒性杂质E(impurity E,Imp-E),按照国际人用药品注册...目的对阿伐那非合成工艺中具有警示结构的潜在有关物质进行致突变性评价研究,为阿伐那非有关物质的分类分级提供指导和依据。方法通过化学方法定向合成阿伐那非含警示结构的潜在遗传毒性杂质E(impurity E,Imp-E),按照国际人用药品注册技术协调会(The InternationalCouncil for Harmonisation of Technical Requirementsfor Pharmaceuticals for Human Use,ICH)M7指导原则对其进行评价和分类。分别采用基于专家规则和统计学原理的2种互补的定量构效关系(quantitative structure-activity relationship,QSAR)评价系统(Derek和Sarah)对Imp-E的遗传毒性进行初步预测,并展开Ames试验对Imp-E进一步验证。结果Imp-E的Derek预测结果为阳性,依据ICH M7指导原则的分类为第3类。在Ames验证试验中,受试物剂量为每皿62.5~1000μg时,无论S9存在与否的情况下,回复突变菌落数均未超过溶剂对照组菌落数的2倍且不呈剂量-反应关系,试验结果显阴性。结论Imp-E的致突变性为阴性,推翻了Derek预测的阳性结果,依据ICH M7中的第5类即非突变性杂质进行控制。展开更多
Acute mountain sickness(AMS) is an illness caused by hypoxia due to rapid ascent to altitudes above 2,500 m. Symptoms include headache,nausea, vomiting, and loss of appetite, all of which usually improve within 1 to 2...Acute mountain sickness(AMS) is an illness caused by hypoxia due to rapid ascent to altitudes above 2,500 m. Symptoms include headache,nausea, vomiting, and loss of appetite, all of which usually improve within 1 to 2 days. However,untreated AMS can progress to life-threatening conditions such as high-altitude cerebral and pulmonary edema(HACE and HAPE, respectively)^([1]).展开更多
Rauvolfia serpentina(L.)Benth.Ex Kurz is a greatly appreciated medicinal plant,well-known for its therapeutic benefits in traditional medicine,particularly in Ayurveda,where the roots and whole plant are used to treat...Rauvolfia serpentina(L.)Benth.Ex Kurz is a greatly appreciated medicinal plant,well-known for its therapeutic benefits in traditional medicine,particularly in Ayurveda,where the roots and whole plant are used to treat a variety of ailments.However,studies focusing on R.serpentina seeds are relatively scarce.Hence,the present study provides a novel approach by analysing the seed oil of R.serpentina extracted using the supercritical-carbon dioxide-fluid-extraction(SCFE)technique.The research employed advanced analytical methods including gas-chromatography with flame ionization detector(GC-FID),gas-chromatography-tandem mass spectrometry(GC-MS/MS),and high performance thin layer chromatography(HPTLC)to characterise the chemical composition of the extracted oil.Functional moieties were evaluated by Fourier transform infrared spectroscopy(FT-IR),while proton nuclear-magnetic-resonance(1H NMR)spectroscopy was utilised to identify the phytometabolites as well as to assess the physico-chemical parameters.The anti-microbial potential of the supercritically extracted oil was demonstrated through its activity against Klebsiella pneumoniae.The inhibitory effects on K.pneumoniae were quantified using the broth microdilution method,showing activity at both minimum inhibitory concentrations(MIC50 and MIC90).Furthermore,the oil was found to be non-genotoxic,as demonstrated by the Ames assay,which showed no mutagenic effects against S.typhimurium and E.coli WP2 uvrA.Since previous reports on R.serpentina seeds and their novel contribution in the field of pharmaceutics are rather limited,the present study is of utmost importance.The study may pave the way for future investigations into the therapeutic potentials of R.serpentina seeds.展开更多
The 40th anniversary of Acta Mechanica Sinica(AMS)marks a milestone of the journal and its incessant pursuit of novelty and excellence.AMS strives for publishing reports pushing the knowledge boundaries and breaking e...The 40th anniversary of Acta Mechanica Sinica(AMS)marks a milestone of the journal and its incessant pursuit of novelty and excellence.AMS strives for publishing reports pushing the knowledge boundaries and breaking engineering limits where mechanics plays a vital role.展开更多
文摘目的对阿伐那非合成工艺中具有警示结构的潜在有关物质进行致突变性评价研究,为阿伐那非有关物质的分类分级提供指导和依据。方法通过化学方法定向合成阿伐那非含警示结构的潜在遗传毒性杂质E(impurity E,Imp-E),按照国际人用药品注册技术协调会(The InternationalCouncil for Harmonisation of Technical Requirementsfor Pharmaceuticals for Human Use,ICH)M7指导原则对其进行评价和分类。分别采用基于专家规则和统计学原理的2种互补的定量构效关系(quantitative structure-activity relationship,QSAR)评价系统(Derek和Sarah)对Imp-E的遗传毒性进行初步预测,并展开Ames试验对Imp-E进一步验证。结果Imp-E的Derek预测结果为阳性,依据ICH M7指导原则的分类为第3类。在Ames验证试验中,受试物剂量为每皿62.5~1000μg时,无论S9存在与否的情况下,回复突变菌落数均未超过溶剂对照组菌落数的2倍且不呈剂量-反应关系,试验结果显阴性。结论Imp-E的致突变性为阴性,推翻了Derek预测的阳性结果,依据ICH M7中的第5类即非突变性杂质进行控制。
文摘Acute mountain sickness(AMS) is an illness caused by hypoxia due to rapid ascent to altitudes above 2,500 m. Symptoms include headache,nausea, vomiting, and loss of appetite, all of which usually improve within 1 to 2 days. However,untreated AMS can progress to life-threatening conditions such as high-altitude cerebral and pulmonary edema(HACE and HAPE, respectively)^([1]).
基金Dr.Anupam Srivastava,Dr.Bhasker Joshi,Patanjali Herbal Research Division for their taxonomical supportsMr.Devendra Kumawat,Patanjali Research Foundation for his help in graphics+1 种基金Mr.Tarun Rajput,Mr.Gagan Kumar for their swift administrative supportsinternal research funds from Patanjali Research Foundation Trust,Haridwar,India.
文摘Rauvolfia serpentina(L.)Benth.Ex Kurz is a greatly appreciated medicinal plant,well-known for its therapeutic benefits in traditional medicine,particularly in Ayurveda,where the roots and whole plant are used to treat a variety of ailments.However,studies focusing on R.serpentina seeds are relatively scarce.Hence,the present study provides a novel approach by analysing the seed oil of R.serpentina extracted using the supercritical-carbon dioxide-fluid-extraction(SCFE)technique.The research employed advanced analytical methods including gas-chromatography with flame ionization detector(GC-FID),gas-chromatography-tandem mass spectrometry(GC-MS/MS),and high performance thin layer chromatography(HPTLC)to characterise the chemical composition of the extracted oil.Functional moieties were evaluated by Fourier transform infrared spectroscopy(FT-IR),while proton nuclear-magnetic-resonance(1H NMR)spectroscopy was utilised to identify the phytometabolites as well as to assess the physico-chemical parameters.The anti-microbial potential of the supercritically extracted oil was demonstrated through its activity against Klebsiella pneumoniae.The inhibitory effects on K.pneumoniae were quantified using the broth microdilution method,showing activity at both minimum inhibitory concentrations(MIC50 and MIC90).Furthermore,the oil was found to be non-genotoxic,as demonstrated by the Ames assay,which showed no mutagenic effects against S.typhimurium and E.coli WP2 uvrA.Since previous reports on R.serpentina seeds and their novel contribution in the field of pharmaceutics are rather limited,the present study is of utmost importance.The study may pave the way for future investigations into the therapeutic potentials of R.serpentina seeds.
文摘The 40th anniversary of Acta Mechanica Sinica(AMS)marks a milestone of the journal and its incessant pursuit of novelty and excellence.AMS strives for publishing reports pushing the knowledge boundaries and breaking engineering limits where mechanics plays a vital role.
