OBJECTIVE:To characterize naringenin(NAR) population pharmacokinetics(PPK) in Chinese women with primary osteoporosis.METHODS:Ninety-eight female patients with primary osteoporosis from the Jingshan,Beixinqiao,Jiaodao...OBJECTIVE:To characterize naringenin(NAR) population pharmacokinetics(PPK) in Chinese women with primary osteoporosis.METHODS:Ninety-eight female patients with primary osteoporosis from the Jingshan,Beixinqiao,Jiaodaokou,Chaoyangmen,and Donghuamen communities in Beijing,China,aged 40 to 80 years,received oral Qianggu capsules(250 mg).Blood samples were collected before and at 0.5,1,2,3,4,6,8,10,12,and 24 h after administration.The concentration of NAR in the blood samples was measured using high performance liquid chromatography-tandem mass spectrometry.PPK analyses were performed with nonlinear mixed-effect modeling software(version 7.1.2,PsN3.2.12).The clearance(C1),central distribution volume(V),absorption rate constant(Ka1),peripheral distribution volume(VII),and inter-compartmental clearance(CLII) were set as parameters and estimated by the base model,covariate model,and final model.Kidney-Yang deficiency[Shenyangxu(SYAX)]and liver-kidney-Yin deficiency(Ganshenyinxu) are patterns of symptoms in Traditional Chinese Medicine that were set as covariates,along with age,height,blood urea nitrogen,serum creatinine,alanine transaminase,aspartate transaminase,and hyperlipidemia.Both stepwise forward and backward procedures were accomplished to build models.The final model was evaluated by internal and external validation,visual predictive check,bootstrap,and leverage analysis.RESULTS:A one compartment open model with first order degradation was the best fitted to the concentration-time profiles following oral administration of NAR.The mean of population parameters of the final model,C1,SYAX on C1,V,Ka1,CLII,and VII,were measured to be 37.6 L/h,0.427 L,123 L/h,0.12/h,0.3056,and 1.446,respectively.Inter-individual variability was estimated and SYAX was identified as a significant covariate.CONCLUSION:The population pharmacokinetic model described in this study could effectively characterize the pharmacokinetic profile of NAR following administration of a single dose of oral Qianggu capsules in Chinese women with prima展开更多
Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese wom...Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling （NONMEM） software. The mean of population parameters clearance （C1）, central distribution volume （V）, absorption rate constant （Kal）, inter-compartmental clearance （C2）, peripheral distribution volume （V2） were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen （BUN）, serum creatinine （Scr）, alanine transaminase （ALT）, aspartate transaminase （AST）, hyperlipidemia, Liver （Gan） Kidney （Shen） yin insufficiency （GSYI）, Kidney （Shen） yang insufficiency （SYI） were set as covariates. Results： The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.展开更多
从骨碎补(Drynaria fortunei)的乙酸乙酯萃取物中分离得到了2个黄酮苷类化合物,结合其理化性质,并通过ESI-MS,IR,1 H NMR,13 C NMR,1 H-1 H COSY,HSQC,HMBC等多种波谱学方法进行结构鉴定,鉴定化合物1和2分别为山奈酚-3-O-β-D-6″′-乙...从骨碎补(Drynaria fortunei)的乙酸乙酯萃取物中分离得到了2个黄酮苷类化合物,结合其理化性质,并通过ESI-MS,IR,1 H NMR,13 C NMR,1 H-1 H COSY,HSQC,HMBC等多种波谱学方法进行结构鉴定,鉴定化合物1和2分别为山奈酚-3-O-β-D-6″′-乙酰基-吡喃葡萄糖-(1→4)-α-L-吡喃鼠李糖苷及山奈酚-3-O-β-D-吡喃葡萄糖-(1→4)-α-L-吡喃鼠李糖苷,并对二者的1 H NMR化学位移信号进行了全归属,纠正了文献中C-5和C-9的归属错误.展开更多
The palaeodiversity of flowering plants in Yunnan has been extensively interpreted from both a molecular and fossil perspective. However, for cryptogamic plants such as ferns, the palaeodiversity remains poorly known....The palaeodiversity of flowering plants in Yunnan has been extensively interpreted from both a molecular and fossil perspective. However, for cryptogamic plants such as ferns, the palaeodiversity remains poorly known. In this study, we describe a new ferny fossil taxon, Drynaria lanpingensis sp. nov. Huang,Su et Zhou(Polypodiaceae), from the late Pliocene of northwestern Yunnan based on fragmentary frond and pinna with in situ spores. The frond is pinnatifid and the pinnae are entirely margined. The sori are arranged in one row on each side of the primary vein. The spores have a semicircular to bean-shaped equatorial view and a tuberculate surface. Taken together with previously described fossils, there are now representatives of three known fossil taxa of Drynaria from the late Pliocene of western Yunnan.These finds suggest that Drynaria diversity was considerable in the region at that time. As Drynaria is a shade-tolerant plant, growing preferably in wet conditions in the understory of forests, its extensive existence may indicate forest vegetation and humid climates in western Yunnan during the late Pliocene.This is in line with results from floristic investigations and palaeoclimatic reconstructions based on fossil floras.展开更多
基金Supported by Grant from Significant Drug Research and Development in Important State Science and Technology Specific And Key Technique Research(Key Issues Research on Re-evaluation of Listed Herbal Hedicine,No.2009ZX09502-030)Visiting Fellow Joint Innovation Research Project of The China Academy of Chinese Medical Sciences(Exploratory Research in Population Pharmacokinetics of Bioactive Compounds of Osteopractic Total Flavone Based on Total Quantum Statistical Moment.No.ZZ070834)
文摘OBJECTIVE:To characterize naringenin(NAR) population pharmacokinetics(PPK) in Chinese women with primary osteoporosis.METHODS:Ninety-eight female patients with primary osteoporosis from the Jingshan,Beixinqiao,Jiaodaokou,Chaoyangmen,and Donghuamen communities in Beijing,China,aged 40 to 80 years,received oral Qianggu capsules(250 mg).Blood samples were collected before and at 0.5,1,2,3,4,6,8,10,12,and 24 h after administration.The concentration of NAR in the blood samples was measured using high performance liquid chromatography-tandem mass spectrometry.PPK analyses were performed with nonlinear mixed-effect modeling software(version 7.1.2,PsN3.2.12).The clearance(C1),central distribution volume(V),absorption rate constant(Ka1),peripheral distribution volume(VII),and inter-compartmental clearance(CLII) were set as parameters and estimated by the base model,covariate model,and final model.Kidney-Yang deficiency[Shenyangxu(SYAX)]and liver-kidney-Yin deficiency(Ganshenyinxu) are patterns of symptoms in Traditional Chinese Medicine that were set as covariates,along with age,height,blood urea nitrogen,serum creatinine,alanine transaminase,aspartate transaminase,and hyperlipidemia.Both stepwise forward and backward procedures were accomplished to build models.The final model was evaluated by internal and external validation,visual predictive check,bootstrap,and leverage analysis.RESULTS:A one compartment open model with first order degradation was the best fitted to the concentration-time profiles following oral administration of NAR.The mean of population parameters of the final model,C1,SYAX on C1,V,Ka1,CLII,and VII,were measured to be 37.6 L/h,0.427 L,123 L/h,0.12/h,0.3056,and 1.446,respectively.Inter-individual variability was estimated and SYAX was identified as a significant covariate.CONCLUSION:The population pharmacokinetic model described in this study could effectively characterize the pharmacokinetic profile of NAR following administration of a single dose of oral Qianggu capsules in Chinese women with prima
基金Supported by Significant Drug Research and Development in Important State Science and Technology Specific and Key Technique Research(No.2009ZX09502-030)
文摘Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling （NONMEM） software. The mean of population parameters clearance （C1）, central distribution volume （V）, absorption rate constant （Kal）, inter-compartmental clearance （C2）, peripheral distribution volume （V2） were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen （BUN）, serum creatinine （Scr）, alanine transaminase （ALT）, aspartate transaminase （AST）, hyperlipidemia, Liver （Gan） Kidney （Shen） yin insufficiency （GSYI）, Kidney （Shen） yang insufficiency （SYI） were set as covariates. Results： The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.
文摘从骨碎补(Drynaria fortunei)的乙酸乙酯萃取物中分离得到了2个黄酮苷类化合物,结合其理化性质,并通过ESI-MS,IR,1 H NMR,13 C NMR,1 H-1 H COSY,HSQC,HMBC等多种波谱学方法进行结构鉴定,鉴定化合物1和2分别为山奈酚-3-O-β-D-6″′-乙酰基-吡喃葡萄糖-(1→4)-α-L-吡喃鼠李糖苷及山奈酚-3-O-β-D-吡喃葡萄糖-(1→4)-α-L-吡喃鼠李糖苷,并对二者的1 H NMR化学位移信号进行了全归属,纠正了文献中C-5和C-9的归属错误.
基金supported by the National Natural Science Foundation of China (31300187,U1502231)the Major Program of National Science Foundation of China (31590823)
文摘The palaeodiversity of flowering plants in Yunnan has been extensively interpreted from both a molecular and fossil perspective. However, for cryptogamic plants such as ferns, the palaeodiversity remains poorly known. In this study, we describe a new ferny fossil taxon, Drynaria lanpingensis sp. nov. Huang,Su et Zhou(Polypodiaceae), from the late Pliocene of northwestern Yunnan based on fragmentary frond and pinna with in situ spores. The frond is pinnatifid and the pinnae are entirely margined. The sori are arranged in one row on each side of the primary vein. The spores have a semicircular to bean-shaped equatorial view and a tuberculate surface. Taken together with previously described fossils, there are now representatives of three known fossil taxa of Drynaria from the late Pliocene of western Yunnan.These finds suggest that Drynaria diversity was considerable in the region at that time. As Drynaria is a shade-tolerant plant, growing preferably in wet conditions in the understory of forests, its extensive existence may indicate forest vegetation and humid climates in western Yunnan during the late Pliocene.This is in line with results from floristic investigations and palaeoclimatic reconstructions based on fossil floras.
