HPLC-ELSD法测定银杏内酯B滴丸中银杏内酯B的含量

目的：建立银杏内酯B滴丸中银杏内酯B的含量测定方法。方法：采用高效液相色谱法。色谱柱为E ZORBAX Eclipse Plus C18（5μm,4.6mm×150mm,Agilent）,流动相为正丙醇-四氢呋喃-水（1∶33∶66）,流速为1.0ml/min,柱温为30℃,采用蒸发光散射检测器（ELSD）检测,外标法测定。结果：银杏内酯B滴丸中银杏内酯B的进样量在1.071～21.42μg（r=0.9996）范围内与各自峰面积对数值呈良好的线性关系;平均加样回收率为98.049%,RSD为0.872%,样品在10小时内稳定。结论：所建立的方法可行,准确、重复性好,适用于银杏内酯B滴丸中银杏内酯B的质量控制。     

反相高效液相色谱法测定银杏叶中银杏萜内酯的含量

银杏萜内酯(ginkgo terpene lactones)为银杏(Ginkgo biloba L.)叶和银杏叶提取物中主要的药效成分,具有广泛的药理作用。银杏叶提取物及其制剂的质量倍受关注。银杏萜内酯为其中最重要的有效成分,其含量测定是非常重要的。银杏萜内酯包括倍半萜白果内酯(bilobalide,BB)和二萜的银杏内酯(ginkgolides)。银杏内酯包括银杏内酯A(ginkgolide A,GA)、银杏内酯B(ginkgolide B,     

高效液相色谱法测定银杏内酯B注射液含量

目的 研究并建立银杏内酯B 注射液的含量测定方法。方法 采用高效液相色谱法,以甲醇-四氢呋喃 水（2.5：1：6.5）为流动相,检测波长为225 nm,测定银杏内酯B 的含量。结果 银杏内酯B在9.98～99.8 μg之间呈良好的线性关系,加样回收率平均值为100.70%,RSD 为0.14%;精密度良好,RSD为0.21%;重复性也很好,RSD为0.21%。结论 该方法稳定可靠,灵敏简便,重复性好,可作为银杏内酯B 注射液的质量控制方法。     

银杏苦内酯B的药理学研究概述

银杏苦内酯为“国宝”银杏叶提取物中的萜类化合物，分为银杏苦内酯A、B、C、M、J和白果内酯，编号分别为BN5加20、BN52021、BN52022、BN52023、BN52024，共约占银杏提取物的6％。银杏提取物中仅含有微量银杏苦内酯B（BN52021），但近年来国内外的研究显示该化合物具有抗炎、抗休克、保护心脑血管、治疗急性胰腺炎等作用。本文对银杏苦内酯B的药理作用进行了概述，为临床应用提供参考。     

HPLC-ELSD法测定白果中银杏内酯A、银杏内酯B和银杏内酯C

目的建立HPLC-ELSD法同时测定白果药材中银杏内酯A、银杏内酯B和银杏内酯C 3个萜杏内酯成分。方法采用Agilent 5TC C18色谱柱(250 mm×4.6 mm,5μm),以甲醇–四氢呋喃–水(25∶10∶65)为流动相,体积流量1 m L/min,柱温30℃,蒸发光散射检测器检测,对照品进样量为10、20μL,供试品溶液进样量为5~20μL。结果银杏内酯A在0.37~5.92μg、银杏内酯B在2.8~44.8μg、银杏内酯C在0.65~10.4μg时线性关系良好。银杏内酯A、银杏内酯B、银杏内酯C平均回收率分别为92.40%、95.03%、91.29%,RSD值分别为2.75%、2.06%、2.88%。结论本法操作简单,重复性好,为白果药材的质量控制提供了依据。     

银杏内酯B对CYP 2C9底物双氯芬酸在大鼠体内药动学和药效学的影响

目的:在大鼠体内,以双氯芬酸为工具药,研究银杏内酯B对双氯芬酸药动学和药效学的影响,阐明银杏内酯B对大鼠肝细胞色素P450 2C9(CYP 2C9)是否有抑制或诱导作用.方法:通过观察大鼠连续给予银杏内酯B(剂量为12 mg·kg-1,ip,bid,连续7 d)前后对单次给予临床等效量的双氯芬酸(15mg·kg-1,iv)的药时曲线及药动学参数的改变,评价其对双氯芬酸药动学的影响,并评价银杏内酯B连续给药后对单次给予双氯芬酸抗足跖肿胀作用药效学的影响.结果:连续给予银杏内酯B后,与用药前比较,双氯芬酸及其主要代谢物4-羟基双氯芬酸的血药浓度及其药动学参数未见显著性改变;双氯芬酸抗足跖肿胀作用亦未见显著性改变.结论:多剂量给予银杏内酯B对临床等效量双氯芬酸在大鼠体内药动学和药效学无显著影响;银杏内酯B对大鼠肝CYP 2C9无明显的抑制或诱导作用.     

银杏内酯B及银杏内酯提取物大鼠体内药动学比较

目的:研究银杏内酯B、银杏内酯提取物在大鼠体内的药动学。方法:LC-MS测定血浆中银杏内酯B的血药浓度,采用3p87药动学处理软件,计算药动学参数,Cmax、tmax采用实测值。结果:银杏内酯B单体、银杏内酯提取物大鼠口服后的t1/2α分别为(0.18±0.09)、(0.17±0.07)h;t1/2β分别为(2.3±2.0)、(2.3±1.5)h;AUC0-12h分别为(2701±655)、(2889±836)μg.L-1.h;AUC0-∞分别为(2778±680)、(2966±854)μg.L-1.h,银杏内酯提取物中银杏内酯B的生物利用度是单体的1.07倍。结论:银杏内酯B单体、银杏内酯提取物大鼠口服后的药动学参数差异均无统计学意义,银杏内酯提取物中共存成分对银杏内酯B的大鼠体内药动学行为影响无统计学意义。     

特异性PAF受体拮抗剂──银杏内酯B在PAF研究、药理研究和临床上的应用

在欧洲主要在德、法两国最大的植物药销售额是银杏提取物制品．1992年有文献报道其销售额为5亿美元，同时指出由于欧洲金字塔型的人口结构，随着老年人口越来越多，销售量仍有增加趋势〔1〕．银杏提取物中有效成分之一为银杏内酯．1932年首先在日本从银杏提取物中分离出一些萜类化合物──银杏内酯（Ginkgolides）．1967年日本研究者确定了这些化合物的结构将它们命名为银杏内酯A，B，C和M，后来又分离出银杏内酯J．它们即是被Braquet及其合作者命名的BN52020，BN52021，BN52022，BN52023和BN52024〔2〕．现在简介其中生理活性最高的…     

银杏浸膏的生物标准化方法

本文建设用测定抑制血小板激活因子（PAF）引起的血小板聚集作为市售银杏浸膏生物标准化的方法，本法对银杏苦内酯A，B，C和J是专一的，并且不受浸膏中其他成分的影响，银杏苦内酯B的IC50值可用于标定由专门方法提取的各种银杏浸膏中等效银杏苦内酯B的含量，为比较化学分析和生物测定的值，必须计算各银杏浸膏中等效银杏总苦内酯的含量，其计算与气相层析结果一致，所以银杏浸膏制剂除化学标准化外，生物标准化也是可行的。     

LC-MS/MS法测定Wistar大鼠组织中银杏内酯B的浓度

目的建立LC-MS/MS法测定大鼠组织中银杏内酯B的浓度,并将此方法应用于银杏内酯B注射液在Wistar大鼠体内的组织分布研究。方法色谱柱:AQVASIL C18柱(100 mm×2.0 mm I.D.,5μm),流动相:乙腈-水-甲酸(体积比为60.0∶40.0∶0.4),流速:0.4 mL.min-1,离子源为电喷雾电离(electrospray ionization,ESI)源,负离子化方式,以选择反应监测(selective reaction monito-ring,SRM)方式进行扫描定量,用于定量分析的离子反应分别为m/z 423→m/z 367(银杏内酯B)和m/z 444→m/z 138(格列吡嗪)。测定了18只Wistar大鼠静脉注射给予银杏内酯B(给药剂量为3.75 mg.kg-1)后大鼠体内各组织和脏器中银杏内酯B的质量浓度。结果测定大鼠组织匀浆液中银杏内酯B的线性为1.0～500.0μg.L-1,定量下限为1.00μg.L-1。低、中、高3个质量浓度质控样品的日内和日间精密度分别小于6.4%和14.5%,准确度为97.3%～103.6%。银杏内酯B在心、肝、脾、肺、肾、胰、胃、小肠、脑、肌肉、脂肪、子宫、卵巢和睾丸14种组织中(除脑组织6 h时间点外)均被检出。银杏内酯B在大鼠各组织中分布广泛,自各组织中消除也较快。结论该方法适用于银杏内酯B注射液在Wistar大鼠体内的组织分布研究。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

洛美沙星体内外抗菌活性研究

洛美沙星对革兰氏阴性菌具有强的抑菌活力。对克氏肺炎杆菌的抗菌活性最强,MIC_(50)为0.12mg/L;对痢疾杆菌、产气杆菌、粘质沙雷氏菌、不动杆菌和枸椽酸杆菌的MIC_(50)分别为1和4mg/L。洛美沙星对肠细菌科细菌的活力比诺氟沙星和依诺沙星强2～16倍,明显地比丁胺卡那霉素、庆大霉素强。对金葡球菌MIC_(50)为1mg/L, MRSA对洛美沙星同样敏感。洛美沙星对表葡球菌、链球菌、粪链球菌及肺炎双球菌等的抗菌活性与地氟沙星相似,比诺氟沙星、依诺沙星、丁胺卡那霉素、庆大霉素和头孢三嗪分别强2～4倍。 洛美沙星对小鼠全身感染的疗效优于诺氟沙星。对大肠杆菌、克氏肺炎杆菌和绿脓杆菌感染小鼠iv的ED_(50)分别是0.74、0.13和3.45mg/kg, po的ED_(50)分别是0.94、1.46和6.20mg/kg。     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

The pathogenesis of,and pharmacological treatment for,Canavan disease

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Protective role of exogenous α-lipoic acid (ALA) on hippocampal antioxidant status and memory function in rat pups exposed to sodium arsenite during the early post-natal period

The present work focussed on the effect of exogenous α-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO₂). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO₂ alone (1.5 and 2.0?mg/kg body wt.) (IIa, IIb) or NaAsO₂ (1.5 and 2.0?mg/kg body wt.) followed by ALA (70?mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4–15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO₂ exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO₂, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO₂ alone as against group Ib and administration of ALA following NaAsO₂ increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO₂ exposure of rat pups on retention memory and oxidative stress markers.     

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ_1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.     

乙酰吉他霉素临床前药理学研究

乙酰吉他霉素对临床分离的革兰氏阳性球菌有较好的抑菌活力，其对金葡球菌、β－溶血性链球菌、表葡球菌的ＭＩＣ_（５０）分别为１、０．２２和４ｍｇ／Ｌ，对耐红霉素、青霉素的金葡球菌、表葡球菌半数以上较敏感，与吉他霉素相似，但其对革兰氏阴性菌无明显作用。乙酰吉他霉素对小鼠实验性细菌感染有明显保护作用。对金葡球菌、肺炎双球菌感染小鼠口服用药的ＥＤ_（５０）分别为７９．６和２５．１ｍｇ／ｋｇ。其疗效与吉他霉素、麦白霉素、乙酰螺旋霉素相似。乙酰吉他霉素小鼠１次口服的ＬＤ_（５０）＞１５ｇ／ｋｇ，与吉他霉素相比毒性无差异。     

大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.