海洋放线菌Kocuria sp.次级代谢产物的研究

目的 研究海洋放线菌Kocuria sp.的次级代谢产物。方法 菌株摇瓶发酵,采用现代色谱学方法(硅胶柱色谱、Sephadex LH-20凝胶柱色谱、半制备HPLC),对发酵产物进行分离,利用现代波谱学技术对化合物进行结构鉴定。结果 从海洋放线菌Kocuria sp.发酵液的乙酸乙酯萃取部分分离得到16个单体化合物：环(L-苯丙氨酸-L-脯氨酸)2 (1)、环(L-色氨酸-L-脯氨酸) (2)、环(L-色氨酸-D-脯氨酸) (3)、环(L-苯丙氨酸-D-脯氨酸) (4)、环(L-羟脯氨酸-L-苯丙氨酸) (5)、环(D-羟脯氨酸-L-苯丙氨酸) (6)、环(L-羟脯氨酸-L-酪氨酸) (7)、环(L-异亮氨酸-D-脯氨酸) (8)、环(L-亮氨酸-D-脯氨酸) (9)、环(L-亮氨酸-L-脯氨酸) (10)、环(L-苯丙氨酸-L-酪氨酸) (11)、环(L-亮氨酸-D-酪氨酸) (12)、环(L-亮氨酸-L-苯丙氨酸) (13)、环(D-缬氨酸-L-苯丙氨酸) (14)、环(D-亮氨酸-甘氨酸) (15)、环(D-异亮氨酸-甘氨酸) (16)。结论 海洋放线菌Kocuria sp.可产生结构丰富多样的环肽类化合物,所有化合物均首次从Kocuria属放线菌中分离得到。     

南海珊瑚内生细菌Brevibacterium sp.中的环二肽成分研究II

目的 对南海珊瑚内生细菌Brevibacterium sp.化学成分进行研究。方法 采用硅胶柱色谱,Sephadex LH-20凝胶柱色谱,高效液相柱层析等分离手段对珊瑚内生细菌Brevibacterium sp.发酵液的乙酸乙酯提取物进行分离纯化,采用NMR、质谱(MS)等现代波谱解析手段,并与文献对照,鉴定化合物结构。结果 分离得到12个已知的环二肽类化合物,其结构分别为环(色-苏)二肽(1)、环(4-羟基-脯氨酸-酪)二肽(2)、环(亮-酪)二肽(3)、环(苯丙-丙)二肽(4)、环(异亮-甘)二肽(5)、环(亮-甘)二肽(6)、环(亮-脯)二肽(7)、环(亮-丙)二肽(8)、环(异亮-丙)二肽(9)、环(亮-苏)二肽(10)、环(异亮-缬)二肽(11)、环(异亮-异亮)二肽(12)。结论 所有化合物均首次从Brevibacterium属中分离得到。     

真菌Penicillium sp. DT-F27次级代谢产物及其活性研究

摘要：目的 一株海洋来源真菌Penicillium sp. DT-F27次级代谢产物及其抗肿瘤活性的研究。方法 采用硅胶柱色谱、反相高效液相制备色谱等方法,对该真菌发酵产物的乙酸乙酯提取物进行分离纯化;采用波普解析方法对化合物的结构进行鉴定;采用MTT法测定化合物对人前列腺癌PC-3细胞的抗肿瘤作用。结果 从真菌Penicillium sp. DT-F27的发酵物中分离得到15个化合物,分别为麦角甾醇（1）,dehydrocyclopeptine（2）,3-O-methylviridicatin（3）,verrucofortine（4）,cyclopenin（5）,cyclo(dehydroala-L-Leu)（6）,cyclopenol（7）,4-hydroxy-2-methoxy acetanilide（8）,trans-(3RS,4RS)-3,4-dihydro-3,4,8-trihydroxynaphthalen-1(2H)-one（9）,cyclo(D-Pro-D-Val)（10）,brevianamide F（11）,cyclo(L-Pro-L-Val)（12）,anacine（13）,cyclo(L-Orn-L-Tyr-L-Orn-L-Ala)（14）,cyclo(L-Pro-L-Tyr)（15）。结论 从真菌Penicillium sp. DT-F27的次级代谢产物中分离15化合物,其中麦角甾醇（1）和3-O-methylviridicatin（3）具有较强的抗肿瘤活性,抑制率分别为45.6%和34.8%。     

海洋放线菌Streptomyces sp.（No.30701）次生代谢产物研究

目的 研究一株海洋放线菌Streptomyces sp.（No.30701）的化学成分。方法 采用硅胶开放柱色谱、Sephadex LH-20凝胶柱色谱以及高效液相色谱等分离手段进行化合物的分离、纯化;利用理化性质和波谱学分析对单体化合物进行结构鉴定。结果 从海洋放线菌Streptomyces sp.（No.30701）发酵物中分离得到9个环二肽类化合物,分别鉴定为环(L-脯-L-缬)二肽（1）、环(D-脯-L-缬)二肽（2）、环(L-脯-L-亮)二肽（3）、环(4-羟基-脯-亮)二肽（4）、环(L-脯-L-异亮)二肽（5）、环(L-脯-L-酪)二肽（6）、环(L-亮-L-缬)二肽（7）、环(D-苯丙-甘)二肽（8）、环(L-苯丙-L-缬)二肽（9）。结论 以上化合物均为海洋放线菌常见的次生代谢产物,但化合物2、8含有天然界中不多见的D型氨基酸,并且化合物2是从链霉菌属放线菌中首次分离得到。     

海洋细菌NJ6-3-1次级代谢产物化学成分的分离与鉴定

目的研究海洋细菌NJ6-3-1次级代谢产物,以期得到有活性的先导化合物。方法采用硅胶柱色谱、凝胶柱色谱、HPLC等方法进行分离纯化,通过理化性质和波谱手段分析确定化合物的结构。结果从海洋细菌NJ6-3-1的乙酸乙酯萃取物中分离得到15个化合物,分别为环(色-脯)二肽(cyclo(Trp-Pro),1)、环(甘-脯)二肽(cyclo(Gly-Pro),2)、环(甘-苯丙)二肽(cyclo(Gly-Phe),3)、环(丙-苯丙)二肽(cylo(Ala-Phe),4)、环(酪-苯丙)二肽(cyclo(Tyr-Phe),5)、环(酪-脯)二肽(cy-clo(Tyr-Pro),6)、环(4-羟基-脯氨酸-苯丙氨酸)(cyclo(4-hydroxyl-Pro-Phe),7)、环(4-羟基-脯氨酸-亮氨酸)(cyclo(4-hydroxyl-Pro-Leu),8)、环(酪-亮)二肽(cyclo(Tyr-Leu),9)、环(丙-亮)二肽(cyclo(Ala-Leu),10)、环(甘-亮)二肽(cyclo(Gly-Leu),11)、环(丙-缬)二肽(cyclo(Ala-Val),12)、异光黄素(isolumichrome,13)、胸腺嘧啶(thymine,14)、尿嘧啶(uracil,15)。结论化合物1~15均为首次从海洋细菌NJ6-3-1次级代谢物中分离得到。     

马缨丹根的化学成分研究

从马缨丹(Lantana camara L.)根的乙醇提取物中分离鉴定出六个寡糖(Ⅰ～Ⅵ)和六个环稀醚萜葡萄糖甙(Ⅶ～Ⅻ),即水苏糖(Ⅰ),毛蕊花糖(Ⅱ),筋骨草糖(Ⅲ),毛蕊花四糖(Ⅳ),α-D-半乳糖-(1[→6-)α-D-半乳糖-(1]₃→6-)D-葡萄糖(Ⅴ),α-D-半乳糖-(1[→6-)α-D-半乳糖-(1]₄→6-)D-葡萄糖(Ⅵ),黄夹子苦甙(Ⅶ),8-表马钱素(Ⅷ),山栀子甙甲酯(Ⅸ),黄夹苦甙(Ⅹ),lamiridoside(Ⅺ)和京尼平甙(Ⅻ)。Ⅴ和Ⅵ是新化合物,分别命名为马缨丹糖A(lantanose A)和马缨丹糖B(lantanose B),其余均首次从该植物中分离得到。     

中国南海石珊瑚Stylophora pistilata化学成分研究

目的 研究中国南海石珊瑚Stylopgora Stylophora pistillata的化学成分。方法 运用硅胶、凝胶(Sephadex LH-20)等多种柱色谱手段对化合物进行分离纯化；利用核磁共振、质谱等波谱学手段并结合其理化性质及文献数据鉴定化合物的结构。结果 从石珊瑚Stylopgora Stylophora pistillata的乙醇提取物中共分离鉴定了8个单体化合物：1,3-十四烷酸甘油二酯（1），正二十五烷（2），正二十三烷（3），肉豆蔻酸（4），2, 2"-氧代双(1, 4-二叔丁苯)（5），(R)-2-乙基己醇（6），2, 2"-bis(4-hydroxyphenyl)propane bis(2,3-epoxypropyl)ether（7）和5-hydroxy-3,4-dimethy-5- pentyl-2(5H)-furanone（8）。结论 化合物1～8均为首次从该石珊瑚中分离得到。细胞毒活性测试结果表明，化合物7对人慢性髓原白血病细胞（K562）、人肝癌细胞（BEL-7402）、人胃癌细胞（SGC-7901）、人肺癌细胞（A549）和人宫颈癌细胞(Hela)的增殖显示出一定的生长抑制活性，其余化合物对上述肿瘤细胞均无生长抑制活性。     

人参芦头抗心律失常活性成分研究

从人参(Panax ginseng C.A.Meyer)芦头中分离得到10个化合物。经理化性质、波谱分析和薄层析分别鉴定为:20(R)-人参皂甙-Rh_1(Ⅰ),人参皂甙-Rg_3(Ⅱ),20(S)-人参皂甙-Rg_2(Ⅲ),-Rg_1(Ⅳ),-B(Ⅴ),-Rd(Ⅵ),-Rc(Ⅶ),-Rb_2(Ⅷ),-Rb_1(Ⅸ),-Ro(Ⅹ).其中化合物Ⅰ,Ⅱ为首次从人参芦头中分离得到的已知成分,并对其中9种主要人参皂甙进行了抗氯化钡诱发大白鼠心律失常作用的研究。     

仙鹤草抗菌活性成分的研究

从仙鹤草地上全草分离得到六种抗菌痢成分,经化学和光谱分析鉴定为:木犀草素—7—葡萄糖甙(Luteolin-7-giucoside)Ⅰ、芹菜素—7—葡萄糖甙(Apigenin-7-giuco-side)Ⅱ、鞣花酸(Ellagic acid)Ⅲ、咖啡酸(Caffeic acid)Ⅳ、没食子酸(Gallic acid)Ⅴ、槲皮素(Quercetin)Ⅵ。以上六种化合物虽属仙鹤草的已知成分,但作为仙鹤草的抗痢有效成分还是首次阐明。抑菌实验表明:上述六种结晶对福氏和志贺氏痢疾杆菌均有抑菌活性,其中Ⅰ、Ⅱ、Ⅲ、和Ⅴ活性较强;结晶Ⅰ+Ⅲ,Ⅱ+Ⅲ,Ⅱ+Ⅳ和Ⅰ+Ⅱ+Ⅵ都比原来单一的化合物抑菌效力强,表明这些化合物之间有协同作用。     

Chemical Study on Alkaloids from Corydalis bulleyana.

Twenty three isoquinoline-type alkaloids were isolated from whole plant of CORYDALIS BULLEYANA Diels. Sixteen of them were identified as known alkaloids, namely, protopine ( 1), (+)consperine ( 2), (+)acetylcorynoline ( 3), dihydrosangunarine ( 4), (+)acetylisocorynoline ( 6), (+/-)stylopine ( 7), (+)corynoline ( 8), (+)corynoloxine ( 9, (+)isocorynoline ( 10), (-)chelanthifoline ( 13), corycavamine ( 14), (+)scoulerine ( 15), (+)isoboldine ( 16), acetylcorydamine ( 18), allocryptopine ( 21) and corydamine ( 23). The remainder were new alkaloids and were referred to as bulleyanine [(6-acetonylacetylisocorynoline)] ( 5), (+)6-acetonylcorynoline ( 11), (+)12-formyloxycorynoline ( 12), (+)6-oxoacetylcorynoline ( 17), (+)12-hydroxycorynoline ( 19), (+)bulleyanaline [(+)6-acetonyl-12-hydroxycorynoline] ( 20) and (+)norjuziphine ( 22), respectively. Their structures have been elucidated by means of spectral and chemical methods.     

单剂量口服匹伐他汀钙片在中国健康志愿者的药代动力学和安全性

目的 研究国产匹伐他汀钙片(降血脂药)在中国健康志愿者体内单次给药的药代动力学特征及安全性.方法 选择中国健康受试者12例,按3×3拉丁方设计,分别单次给予匹伐他汀钙片1,2,4 mg后,采用液相色谱-串联质谱联用法测定不同时间血中匹伐他汀的浓度,以DAS 2.0软件进行数据处理,求算药代动力学参数.结果 3个不同剂量组匹伐他汀的主要药代动力学参数:t_(1/2β)分别为(11.39±7.66),(10.00±7.30),(11.30±7.95)h;t_(max)分别为(0.83±0.29),(0.73±0.20),(0.85±0.46)h;C_(max)分别为(30.48±11.66),(60.80±22.97),(120.98±35.51)ng·mL~(-1);AUC_(0→72h)分别为(93.19±26.61),(179.46±52.86),(364.37±94.74)ng·mL~(-1)·h;AUC_(0→∞)分别为(96.70±27.42),(183.34±53.62),(372.86±95.84)ng·mL~(-1)·h;各剂量组的C_(max)、AuC_(0-72h)、AUC_(0→∞)随剂量的增加而成比例的增大,各组的K_(10)、t_(max)、t_(1/2β)、MRT_(0-72)、MRT_(0→∞)、CL/F、V/F等差异无统计意义.结论 口服给药剂量为1～4 mg时,匹伐他汀钙片在中国健康人体内具有线性药代动力学特征,其代谢特征基本与文献报道一致.     

Characterization of flavonoids in the extract of Sophora flavescens Ait. by high-performance liquid chromatography coupled with diode-array detector and electrospray ionization mass spectrometry

A method coupling high-performance liquid chromatography (HPLC) with diode-array detector (DAD) and electrospray ionization mass spectrometry (ESI) was established for the separation and characterization of flavonoids in Sophora flavescens Ait. Based on the chromatographic separation of most flavonoids present in S. flavescens Ait., a total of 24 flavonoids were identified. Fourteen compounds were unambiguously identified comparing experimental data for retention time (t(R)), UV and MS spectra with those of the authentic compounds: 3',7-dihydroxy-4'-methoxy-isoflavone (13), trifolirhizin (14), kurarinol (18), formononetin (19), 7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (22), maackiain (21), isoxanthohumol (23), kuraridine (26), kuraridinol (27), sophoraflavanone G (30), xanthohumol (31), isokurarinone (33), kurarinone (35) and kushenol D (38), and additional 10 compounds were tentatively identified as kushenol O (10), trifolirhizin-6'-malonate (15), sophoraisoflavanone A (20), norkurarinol/kosamol Q (24), kushenol I/N (25), kushenol C (28), 2'-methoxykurarinone (29), kosamol R (32), kushecarpin A (34) and kushenol A (37) by comparing experimental data for UV and MS spectra with those of literature. Furthermore, fragmentation pathways in positive ions mode of 24 flavonoid compounds of types of flavanone, flavanonol, flavonol, chalcone, isoflavone, isoflavanone and ptercocarpane were summarized. Some common features, such as CH(3)., H(2)O, CO, CO(2), C(3)O(2) and C(2)H(2)O losses, together with Retro-Diels-Alder fragmentations were observed in the prenylated flavonoids in S. flavescens Ait. The loss of the lanandulyl chain was their characteristic fragmentation, which might help deducing the structure of unknown flavonoid compounds. The present study provided an approach to rapidly characterize bioactive constituents in S. flavescens Ait.     

Multiple dose pharmacokinetics of quetiapine and some of its metabolites in Chinese suffering from schizophrenia

INTRODUCTION Quetiapine (QTP) is a novel atypical antipsychoticwhich is as effective as traditional antipsychotics. Itcauses less extrapyramidal side effects, hyperpro-lactinmia, QT interval prolongation, and agranulocyto-sis than other neuroleptics[1-3]. The commonly usedeffective dose ranged from 25 to 300 mg per day andeven over to 750 mg per day. In vivo, quetiapine sulfoxide (QTP-SF) is the ma-jor inactive metabolite. 7-Hydroxy-quetiapine (QTP-H) and 7-hydroxy-N-dealkyl-quetiap…     

左旋氨氯地平对高血压患者血管内皮细胞生长因子影响

目的 研究高血压患者血管内皮细胞生长因子(VEGF)与左室肥厚(LVH)的关系以及左旋氨氯地平对VEGF的干预作用.方法 62例轻、中度原发性高血压患者,根据左室质量指数(LVMI)分左室肥厚组(30例)和非肥厚组(32例),2组患者均给予左旋氨氯地平2.5-5 mg/d,共8周.同时选择同期健康体检的27例健康者作为对照组.比较3组之间以及2组高血压患者之间治疗前后血清肌酐(Cr)、谷丙转氨酶(ALT)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固酵(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、超敏C反应蛋白(hsCRP)、空腹血糖(FBG)和餐后2h血糖(2hBG)以及VEGF水平的差异.比较VEGF与其他指标的关系.结果 1)2组高血压患者的VEGF均显著高于对照组(P＜0.01),左室肥厚组的VEGF显著高于非肥厚组(P＜0.05).2)VEGF与LVMI正相关(R =0.391,P＜0.01).3)左旋氨氯地平2.5～5 mg/d治疗8周,可以有效地降低轻中度高血压患者的SBP,DBP,TC,LDL-C,hsCRP和VEGF.结论 1)高血压患者的VEGF升高,伴左室肥厚者更为严重.2)左旋氨氯地平可以降低轻中度高血压患者VEGF水平.     

2型糖尿病伴发脂肪肝的临床特点

目的探讨2型糖尿病伴发脂肪肝的临床特点。方法测定32例2型糖尿病伴发脂肪肝和30例2型糖尿病不伴发脂肪肝病例的空腹血糖(FBG),空腹胰岛素(FINS),血脂谱及肝功能,计算体重指数(BM I)及胰岛素敏感指数(ISI)。结果2型糖尿病伴发脂肪肝与不伴发脂肪肝者相比,体重指数(BM I),甘油三脂(TG),总胆固醇(TC),低密度脂蛋白胆固醇(LDL-C),谷丙转氨酶(ALT),谷草转氨酶(AST),谷氨酰转肽酶(r-GT),空腹胰岛素(FINS)均升高(<0.05,P<0.01),而高密度脂蛋白胆固醇(HDL-C),胰岛素敏感指数(ISI)则降低(P<0.05,P<0.01)。结论2型糖尿病伴发脂肪肝比不伴发脂肪肝者存在明显的体重指数增高、脂代谢紊乱、肝功能异常及胰岛素抵抗     

番荔枝种子化学成分研究

目的研究药用植物番荔枝(Annona squamosa L)种子的抗肿瘤活性成分。方法利用各种色谱技术进行分离纯化, 根据化合物的理化性质和光谱数据鉴定化学结构。结果从乙醇提取物分离鉴定了11个番荔素: squamocenin (1), annotemoyin-2 (2), reticulatain-2 (3), squamocin-I (4), squamocin-B (5), squamocin (6), motrilin (7), squamostatin-D (8), squamostatin-E (9), cherimolin-1 (10)和cherimolin-2 (11)。结论Squamocenin (1)为新番荔素; annotemoyin-2 (2)和reticulatain-2 (3)是首次报道该植物含有的化合物。     

Molecular basis of resistance to macrolides and lincosamides among staphylococci and streptococci from various animal sources collected in the resistance monitoring program BfT-GermVet

In this study, erythromycin- and/or clindamycin-resistant isolates among 248 coagulase-positive and coagulase-variable staphylococci and 500 streptococci, collected all over Germany during 2004-2006 in the resistance monitoring program BfT-GermVet, were investigated for their genetic basis of macrolide and/or lincosamide resistance. Staphylococci were sampled from various disease conditions of dogs/cats or pigs, whereas streptococci were from dogs/cats, pigs or horses. Resistant staphylococci were further identified biochemically to species and subspecies level and tested for the resistance genes erm(A), erm(B), erm(C), erm(TR), msr(A), msr(D), mef(A), mph(C), lnu(A), lnu(B) and lnu(C). The methylase genes erm(A), erm(B) and erm(C) were detected in staphylococci, alone or in different combinations. The erm(B) gene was the predominant gene in Staphylococcus intermedius and streptococci. The efflux gene msr(A) and the genes mph(C) and lnu(A) coding for inactivating enzymes were detected in single staphylococcal isolates. The efflux genes mef(A) and msr(D) were detected in three streptococci, in one of them together with the erm(B) gene. The lnu(B) gene was detected in seven porcine streptococcal isolates with reduced susceptibility to clindamycin. These data confirm that high-level resistance to erythromycin and clindamycin in staphylococci and streptococci was mainly due to rRNA methylases. The lnu(B) gene was detected for the first time in streptococci of animal origin.     

Minor Saponins from the Leaves of Panax ginseng C.A. Meyer

<正> Five minor compounds isolated from the leaves of Panax ginseng C. A. Meyer were characterized as 20(R)-protopanaxatriol (1), daucosterin (2), 3β, 12β-dihydroxy-dammar-20 (22), 24-diene-3-O-β-D-glucopyranoside (3), 20 (R)-protopanaxadiol-3-O-β-D-glucopyranoside (4) and ginsenoside-Rh_2 (5), respectively, on the basis of spectral analyses and chemical evidence. The two new saponins, 3 and 4, were named as ginsenoside-Rh_3 and 20(R)-ginsenoside-Rh_2.Nine other major saponins obtained simultaneously were identical with ginsenoside-Rh_1(6),-Rg_3 (7), -Rg_2 (8), -Rg_1 (9),-Re(10),-Rd (11), -Rc (12), -Rb_2(13) and Rb_1 (14), respectively.     

叶枯灵在大鼠尿内的代谢产物分析

大鼠ig叶枯灵后,用HPLC和TLC分离纯化尿提取液中的叶枯灵及其代谢产物,得到六个组分,经MS和UV初步鉴定为叶枯灵,苯甲酸,马尿酸和三个新化合物:肼叉-1.3-二噻茂烷,乙酰肼叉-1.3-二噻茂烷和丙酮酸缩肼叉-1.3-二噻茂烷,通过对代谢物的化学合成,进一步确证了它们的化学结构。     

Pharmaceutics: The Effect of Dose on the Characterization of Aerodynamic Particle-size Distributions of Beclomethasone Dipropionate Metered-dose Inhalers

The aerodynamic particle-size distribution for two doses of a Becloforte metered-dose inhaler (MDI) was measured by use of a twin-stage impinger (TSI), the new multi-stage (five-stage) liquid impinger (MSLI) and the Andersen cascade impactor (ACI) (n = 5 for each apparatus). The mean (s.d.) fine-particle doses measured by the three techniques for the Becloforte MDI were 40.3 (1.2), 45.7 (0.5) and 41.8 (0–4)% w/w, respectively; the median mass aerodynamic diameters (MMAD) measured using the MSLI and the ACI were 3.50 and 3.73 μm, respectively. The MSLI fine particle (< 6.8 μm) doses for 2, 5, 10, 20, 30 and 40 doses from Becloforte MDIs (n = 5 for each dose) were 49.7 (0.7), 52.9 (1.2), 45.3 (0.6), 45.5 (0.71), 45.9 (0.7) and 46.4 (0.7)% w/w, respectively. Values obtained using the ACI (< 5.8 μm) were 40.8 (1.0), 41.0 (0.8), 44.4 (0.5), 43.1 (0.4), 42.8 (0.5) and 40.4 (0.4)% w/w (n = 4). MMAD values measured with the MSLI were 3.39, 3.46, 3.75, 3.91, 4.15 and 4.45 μm, respectively; using the ACI they were 3.46, 3.54, 3.61, 3.66, 3.73 and 3.85 μm. The results indicate that the measured aerodynamic particle-size distributions of beclomethasone dipropionate MDIs are affected by the dose dispensed and by the apparatus used for measurement.