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Pharmacokinetics of CPU0213,a novel endothelin receptor antagonist,after intravenous administration in mice

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Acta Pharmacologica Sinica 2006年第3期27卷 367-371页

作者： Li GUAN~2 Yu FENG~2 Min JI~4 De-zai DAI~(2,3) ~2Research Division of Pharmacology,and ~4Center of New Drug Research and Development.china pharmaceutical university,Nanjing 210009.china ResearchDivisionofPharmacology ChinaPharmaceuticalUniversityNanjing210009China CenterofNewDrugResearchandDevelopment.chinapharmaceuticaluniversity Nanjing210009China

Aim:To determine the pharmacokinetics associated with acute toxic doses ofCPU0213,a novel endothelin receptor antagonist in mice after a single intrave-nous ***:Concentrations in serum and the pharmacokineticparameters of CPU0213 were assayed by high pressure liquid chromatography(HPLC)following a single intravenous bolus of CPU0213 at concentrations of 25,50,and 100 mg/kg in *** intravenous acute toxicity of CPU0213 was alsoassessed in ***:A simple,sensitive and selective HPLC method wasdeveloped for quantitative determination of CPU0213 in mouse *** con-centration-time data conform to a 2-compartment model after iv administration ofCPU0213 at concentrations of 25,50,100 mg/*** corresponding distributionhalf-lives(T1/2α) were 3.6,4.2,1.1 min and the elimination half-lives(T1/2β)were39.4,70.3,61.9 *** was a linear increase in C0proportional to dose,and thesame as AUC0-tand AUC0-∞.AUC0-tand AUC0-∞were 4.511,13.070,23.666 g·min·L-1and 4.596,13.679,24.115 g·min·L-1,*** intravenous LD50was 315.5mg/***:First order rate pharmacokinetics were observed for CPU0213within the range of doses used,and the acute toxicity of CPU0213 is mild.

关键词： CPU0213 high pressure liquid chromatography mice pharmacokinetics acute toxicity

The permeability of blood-brain barrier under CNS-related diseases and the clinical significances

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The permeability of blood-brain barrier under CNS-related di...

第九届全国药物和化学异物代谢学术会议

作者： LIU Hai-yan~(1,2),LIU Xiao-dong~(1*) 1 Center of Drug Metabolism and Pharmacokinetics,china pharmaceutical university.Nanjing 210009, Jiangsu,china 2 Central Research Institute of Shanghai pharmaceutical(Group) Co.Ltd., Shanghai pharmaceutical(Group) Co.Ltd.,Shanghai 201203,china

Blood-brain barrier(BBB) consists of the cerebral microvessel endothelial cells connected by complex tight junctions,which regulates the homeostasis of the neural milieu rather than simply impeding solute exchange between blood and *** endothelial cells express numerous highly specific proteins that play important roles in substance transport,enzymatic,receptor and cell-mediated mechanisms in brain. Circulating compounds are transported across BBB in different mechanisms including:(1) lipid-mediated transport of many small highly lipophilic compounds;(2) carrier- mediated transport of hydrophilic nutrients and their analogs;(3) plasma protein-mediated transport of acidic compounds,peptides and highly lipophilic conpounds;(4) receptor and/ carrier-mediated transcytosis of peptides and proteins;(5) absorptive-mediated transcytosis of polycationic proteins;and (6) non-specific bulk flow ***,important finding is that a series of transporters have been identified in microvessel endothelial cells,including glucose transporters,amino acid transporters,polypeptide transporters,MDR1 (P-glycoprotein,P-GP),the breast cancer resistance proteins(BCRP),the multidrug resistance-associated proteins (MRPs),the organic anion transport proteins(Oatps),and the organic anion transporters(OATs).P-GP,BCRP and MRPs belong to ATP-binding cassette(ABC) transporter *** of the transporters are transmembrane proteins and located in the luminal or abluminal membranes of the endothelial *** transporters,to some extents,are involved in mediating transport of compounds across BBB. Under the physiological state,BBB is generally considered as a mechanism for protecting the brain from unwanted actions resulting from substances in the blood and maintaining brain homeostasis via monitoring the entry or efflux of compounds. However,certain diseases may increase or decrease BBB permeability,inducing alteration in pharmacological or toxicological activity of dru

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追求“涌现”——科技创新研发团队的管理新理念

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系统科学学报 2010年第4期18卷 42-44,90页

作者：罗蕾吴晓明中国药科大学江苏南京210009

本文从复杂性系统演化的不可预测性,论述传统的绩效评估方法在科技创新研发团队管理上的局限,并通过科技创新研发系统决策"涌现"产生根源的考察和分析,说明管理行为"介入"对于科技创新研发系统演化产生影响的可能性,由此提出以促进系统... 详细信息

本文从复杂性系统演化的不可预测性,论述传统的绩效评估方法在科技创新研发团队管理上的局限,并通过科技创新研发系统决策"涌现"产生根源的考察和分析,说明管理行为"介入"对于科技创新研发系统演化产生影响的可能性,由此提出以促进系统"涌现"生成为目标的科技创新研发团队管理理念。

关键词： “涌现” 科技创新研发管理理念

Two New Oleanene-Type Triterpenoid Saponins from Pueraria peduncularis

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Chinese Chemical Letters 2000年第4期11卷 343-346页

作者： Na Ll~1 Zhi Da MIN~1 Hou Ming WU~2 (1 Department of Natural Products Chemistry, china pharmaceutical university, Nanjing 210009 2 State Key.Laboratory of Bio-organic and Natural Products Chemistry. Shanghai Institute of Organic Chemistry. Chinese Academy china Pharmaceut Univ Dept Nat Prod Chem Nanjing 210009 Peoples R China Chinese Acad Sci Shanghai Inst Organ Chem State Key Lab Bioorgan & Nat Prod Chem Shanghai 200032 Peoples R China

From the radix of Pueraria peduncularis Grah., two new oleanene-type triterpenoid saponins named pedunsaponins B (2) and C (3) were isolated. Their structures were determined as 3-O-(6-O-methyl)-beta-D-glucuronopyranosyl-3 beta.15 alpha-diol-12-oleanene-16-one (2) and 3-O-beta-D-glucopyranosyl-( 1 --> 3)-beta-D-glucuronopyranosyl-3 beta, 15 alpha-diol-12-oleanene-16-one (3) on the basis of spectroscopic evidence and chemical reactions.

关键词： Pueraria peduncularis Leguminosae triterpenoid saponin

PPARγ agonist pioglitazone reverses memory impairment and biochemical changes in a mouse model of type 2 diabetes

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PPARγ agonist pioglitazone reverses memory impairment and b...

第十五届中国神经精神药理学学术会议

作者： JIANG Li-ying~1,TANG Su-su~1,WANG Xiao-yun~1,LIU Li-ping~2, LONG Yan~1,HU Mei~1,LIAO Ming-xing~3,DING Qi-long~3, HU Wei~2,LI Jia-chang~3,HONG Hao~1 (1.Department of Pharmacology,china pharmaceutical university, Nanjing 210009,china 2.Department of Pharmacy,the Second Hospital Affiliated to Anhui Medical university,Hefei 230031,china 3.Experimental Instruction Center of pharmaceutical & Medical Basic,china pharmaceutical university, Nanjing 210009,china)

OBJECTIVE Pioglitazone,known as a peroxisome proliferator-activated receptorγ(PPARγ) agonist,is used to treat type 2 diabetes(T2DM).T2DM has been associated with reduced performance on numerous domains of cognitive function. Here,we investigated the effects of pioglitazone on memory impairment in a mouse model with defects in insulin sensitivity and secretion,namely high-fat diet(HFD) streptozotocin(STZ)-induced diabetic *** ICR mice were fed an HFD for 4 weeks and then injected with a single low dose of STZ followed by continued HFD feeding for an additional 4 *** diabetic mice were orally administered with pioglitazone(9,18 mg·kg) for 4 - 5 weeks.Y-maze test and Morris water maze test(MWM) were employed for testing learning and memory. Serum glucose,serum insulin,serum triglyceride,brain amyloid peptide-β(Aβ),brainβ-site amyloid precursor protein cleaving enzyme(BACE1),brain nuclear factor kB(NF-κB),brain receptor for advanced glycation end products(RAGE) were also *** The STZ/HFD diabetic mice,characterized by hyperglycemia,hyperlipemia and hypoinsulinemia,performed poorly on Y-maze and MWM hence reflecting impairment of learning and memory behavior with increases of Aβ/Aβ, BACE1,NF-κB,and RAGE in *** of PPARγagonist, pioglitazone,significantly reversed diabetes-induced impairment of learning and memory behavior,which is involved in decreases of Aβ/Aβ via inhibition of NF-kB,BACE1 and RAGE in brain as well as attenuation of hyperglycemia,hyperlipemia and *** It is concluded that PPARγagonist pioglitazone may be considered as potential pharmacological agents for the management of cognitive dysfunction in T2DM.

关键词： pioglitazone cognition β-amyloid BACE1 NF-κB diabetes mellitus

HP-β-环糊精对盐酸舍曲林异构体手性选择包合和色谱保留行为影响的研究

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色谱 2004年第6期22卷 595-600页

作者：陈德英陈玉英胡育筑中国药科大学江苏南京210009

研究了不同色谱条件下HP β 环糊精(HP β CD)作为反相高效液相色谱(RP HPLC)手性添加剂对盐酸舍曲林异构体的手性选择性和色谱保留行为的影响。通过保留因子(k)的倒数1/k对[HP β CD]的良好线性关系证明HP β CD与盐酸舍曲林异构体形... 详细信息

研究了不同色谱条件下HP β 环糊精(HP β CD)作为反相高效液相色谱(RP HPLC)手性添加剂对盐酸舍曲林异构体的手性选择性和色谱保留行为的影响。通过保留因子(k)的倒数1/k对[HP β CD]的良好线性关系证明HP β CD与盐酸舍曲林异构体形成了包合比为1∶1的包合物,并通过1/k对[HP β CD]的直线求得其结合常数。同时系统研究了pH值、缓冲液浓度(离子强度)、乙腈溶剂强度及温度对结合常数的影响,对结合常数与它们的关系做出了定量的描述;计算了手性分离过程中的热力学参数,并结合所计算的结合常数,研究了HP β CD对盐酸舍曲林异构体的手性识别能力的影响。结果表明,HP β CD与盐酸舍曲林异构体相互作用的结合常数的大小顺序与手性分离选择性的顺序相反,焓差(△j,i△H)和熵差(△j,i△S)越大,手性分离选择性也越大。实验得到的盐酸舍曲林异构体的焓差和熵差都是负值,说明盐酸舍曲林异构体的分离是焓驱动的分离过程;温度对结合常数影响的实验结果表明,HP β CD对盐酸舍曲林异构体的包合过程是一个放热行为,与通过计算热力学参数得到的结果一致。

关键词：高效液相色谱法结合常数手性分离环糊精盐酸舍曲林异构体

Influence of Borneol on In Vitro Corneal Permeability and on In Vivo and In Vitro Corneal Toxicity

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Influence of Borneol on In Vitro Corneal Permeability and on...

第十届全国中西医结合眼科学术会议暨第五届海峡眼科学术交流会

作者： Yang H Xun Y Li Z Hang T Zhang X Cui H Department of Ophthalmology,The First Affiliated Hospital,Harbin Medical university,Harbin, china Centre for Instrumental Analysis,china pharmaceutical university,Nanjing,china

Influence of Borneol on In Vitro Corneal Permeability and on In Vivo and In Vitro Corneal Toxicity |OCULAR DISEASE;RABBITS;BORNEOL;CHINESE MEDICINE;OCULAR DRUG DELIVERY;CORNEAL PENETRATION;CORNEAL TOXICITY;CORNEAL HYD...

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Chemical studies on three species of Dendrobium

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Chemical studies on three species of Dendrobium

The 3～(rd) International Conference on Natural Products :Natural Products -a Must for Human Survival ABSTRACTS

作者： Zhengtao Wang, Li Yang, Guangnong Zhang, Ping Lin, Luoshan Xu Department of Pharmacognosy, china pharmaceutical university, Nanjing 210038

Shihu is a noble traditional Chinese medicine with the function to benefit stomach, to promote the production of body fluid, to nourish yin and to remove excessive heat. According to the Chinese Pharmacopoeia, it is the fresh or dried stem of Dendrobium loddigesii, D. fimbriatum var. oculatum, D. chrysanthum, D. candidum or D. nobile. But the origins of commercial drug were very confused because of the lacking of the drug resources. There are about 20 species belonging to 3 genera sold in market. In order to learn and compare the chemical constituents and the pharmacological effects of different species of Dendrobium, the chemical researches of three plants in the genus, Dendrobium chrysanthum, D. nobile and D. thyrsiflorum, were carried *** investigations of Dendrobium chrysanthum, D. nobile and D. thyrsiflorum have resulted in the isolation of 39 compounds including 5 new compounds. Their structures were identified on the basis of IR, UV, NMR, MS spectra, physicochemical properties and literature data. The results were shown as following:Seventeen compounds isolated from D. chrysanthum were chrysotobibenzyl (1), crepidatin (2), moscatilin (3), dengibsin (4), dendroflorin (5), emodin (6), physcion (7), chrysophanol (8), sitosterol (9), n-hexadecane (10), defuscin (11), n-triacontyl p-hydroxy- cis-cinnamate (12), n-octacostyl ferulate (13), daucosterol (14), trans - dendrochrysanine (15), cis - dendrochrysanine (16) and dendrochrysanene (17).Eight compounds obtained from D. nobile were dengibsin (4), dendroflorin (5) chrysophanol (8), dendropene A (18), dendropene B (19), dendrobine (20), dendramine (21) and 2,4,7-trihydroxy - 1, 5 - dimethoxy - 9 - fluorenone (22).Twenty-three compounds obtained from D. thyrsiflorum were moscatilin (3), dengibsin (4), dendroflorin (5), emodin (6), physcion (7), chrysophanol (8), denchrysan A (23), denchrysan B (24), gigantol (25), trisin (26), moscatin (27), hircinol (28), coumarin (29), scopoletin (30), scoparone (31), ay

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蕨类植物的黄酮类成分及其系统学意义

武汉植物学研究 1989年第4期7卷 377-389页

作者：周铜水中国药科大学植物化学分类研究室

蕨类植物的黄酮类成分以比较原始的结构类型为主,少数类群也拥有相当进化的类型。双黄酮,黄酮醇,白花色甙及原花色甙对于蕨类植物的系统学研究具有重要意义。化学证据表明小叶型蕨类较大叶型真蕨类原始,厚囊蕨类较薄囊蕨类原始等。

关键词：蕨类植物黄酮类系统学