海洋长孢葡萄穗霉菌生物合成纤溶活性化合物的研究

目的 基于FG216（Fungus stachytotrys longispora）产生纤溶化合物FGFC1（Fungi fibrinolitic compound 1）的可能生源途径,调控其次生代谢过程,获得新型纤溶活性或者其他活性化合物。方法 FG216经过种子培养和发酵培养,在发酵培养结束前24 h,添加ADP、色氨酸、柠檬酸三钠、赖氨酸、苯丙氨酸、组氨酸、鸟氨酸、天冬酰胺等8种代谢产物调节剂（metabolite regulator,MTRL）,添加量为发酵液的1%,用HPLC（High-pressure liquid chromatogram）检测FG216代谢产物产出情况。结果 添加鸟氨酸为MTRL的FGFC1的产量增加至950 mg/L,苯丙氨酸为MTRL的FG216代谢产物的HPLC图谱出现2个新的化合物峰。色氨酸为MTRL的FG216代谢产物的HPLC图谱出现3个新的化合物峰。ADP、柠檬酸三钠、赖氨酸、组氨酸、天冬酰胺为MTRL的FG216代谢产物的HPLC图谱未出现新的化合物峰。分离纯化5种目标化合物CA、CB、CC、CD、CE在纤溶活性评价反应体系（10 μg/mL）,其纤溶活性分别是FGFC1的30%、90%、50%、110%、17%。结论 采用恰当的FG216发酵MTRL,能产生新型的纤溶活性化合物,推测通过调控代谢生源途径,能从FG216挖掘出活性更强或结构新颖的纤溶化合物。     

黑黏座孢霉二次代谢产物的两个活性成分

目的研究云南省西双版纳采集的土样中黑黏座孢霉(Myrothecium roridumTode ex Fr.)发酵液的活性成分。方法通过硅胶柱色谱、制备薄层色谱、HPLC等手段进行分离纯化,并根据理化性质和光谱数据鉴定其化学结构。结果从黑黏座孢霉发酵液乙酸乙酯提取物中共分离得到2个化合物,经鉴定分别为黏液霉素A(verrucarin A)和黏液霉素J(verrucarin J),并利用稻瘟霉(Pyricu-laria oryzae)菌丝体形态变化作为活性指标,测定了它们的活性。结论黏液霉素A和J为首次从该菌种中分离得到。     

聚醚类抗生素61477的研究 Ⅱ.抗生素61477的理化特性及其鉴别

本文论述从白色链霉菌疣孢变种614F7菌株发酵液中分离得到的抗生素的理化特性及其鉴别。 抗生索61477的纯品与从市售饲料添加剂中分离得到的盐霉素以及文献报道有关盐霉素的理化数据相比较,我们认为,抗生素61477与盐霉素基本一致。     

灰绿葡萄孢发酵液中天然型脱落酸的分离纯化

对脱落酸产生菌灰绿葡萄孢(Botrytis cinerea)发酵生产脱落酸的分离纯化工艺进行了初步探索。发酵液经过滤、浓缩、去杂、乙酸乙酯萃取、NaHCO3反萃取、硅胶柱层析、结晶等步骤进行分离纯化可得脱落酸，测定总收率可达39.7％。产品经光谱测定、旋光测定证实为天然型脱落酸，纯度在98%以上。     

真菌G-18代谢产物的研究——Ⅱ.免疫抑制剂G-18-Ⅳ的分离鉴别

从多孢木霉(Trichoderma polysporum)的发酵液中,分离到一组具有免疫抑制作用的物质-G-18-Ⅰ、G-18-Ⅱ、G-18-Ⅲ、G-18-Ⅳ,其中G-18-Ⅳ为在红外光谱2100cm~(-1)具有强吸收的异腈类化合物,基于理化性质及光谱数据,已鉴别G-18-Ⅳ为异腈素酸E(木菌素)甲酯。     

微紫青霉对莪术醇的定向转化

使用微紫青霉对莪术醇(1)进行生物转化,采用硅胶柱色谱法从发酵液的乙酸乙酯萃取层中分离得到转化产物(2),利用理化及各种光谱手段鉴定其结构为15-羟基莪术醇.微紫青霉对莪术醇具有定向转化能力,获得转化产物的收率为24%,该转化产物为未见文献报道的新化合物.利用二维核磁共振等手段对其碳、氢信号进行了全归属.体外试验表明:化合物2对副流感病毒、呼吸道合孢病毒和单纯疱疹病毒I型具有较好的抑制作用.     

海洋微生物来源纤溶活性化合物的筛选及其分离

目的 从海洋微生物的次生代谢产物中分离具有纤溶促进作用的化合物.方法 采用选择性培养基从海水样品中分离细菌、真菌和放线菌,利用发色底物法筛选产纤溶活性化合物的菌株和确定菌株发酵培养基,通过HPLC分离活性化合物.结果 从离岸100 m处采集的31个海水样品中获得分离菌株936个,从霉菌FG216的次生代谢产物中,发现了具有纤溶促进作用的活性化合物,采用改良的察氏培养基作为发酵培养基,代谢产物的纤溶促进效果最好,并从FG216的发酵液中分离和精制了活性化合物.结论 从海洋微生物的代谢产物中得到了具有纤溶促进作用的活性化合物.     

弯孢马利亚霉SⅡA-F12361次级代谢产物研究

目的 对稀有丝状真菌弯孢马利亚霉的次级代谢产物进行化学研究.方法 采用系统发酵和基于HPLC-DAD分析技术的化学筛选法,对弯孢马利亚霉SIIA-F12361的次级代谢产物谱进行分析,并对主要次级代谢产物进行分离纯化和结构鉴定.结果 从菌株SIIA-F12361发酵液中分离获得肽波霉素类化合物2个,脂肪酸类化合物2个,环二肽化合物2个.结论 所有化合物均为首次在马利亚霉属中发现.     

产紫青霉中的活性成分

从陕西省采集的土样中分离得到产紫青霉 (Penicillium purpurogenumStoll) ,从其发酵液乙酸乙酯萃取物中分离得到两个化合物 ,经过光谱数据的分析鉴定为 :3 (1′ 羧基乙烯氧基 )苯甲酸和间羟基苯甲酸 ,并利用稻瘟霉 (Pyriculariaoryzae)菌丝体形态变化作为活性指标 ,测定了它们的活性     

氨基糖苷类抗生素M—41—A的分离和鉴别

从橄榄星孢小单孢菌M－41的发酵液中分离到氨基糖苷类抗生素M－41－A,基于理化性质和光谱数据,抗生素M－41－A已鉴别为Verdamicin。     

海洋纤溶活性化合物FGFC1和FGFC2影响血小板聚集特性的研究

目的：研究新型海洋双吲哚纤溶活性化合物FGFC1对血小板聚集的影响,发现纤溶活性化合物FGFC1与血小板相关因子变化的关系,同时比较双吲哚化合物FGFC1和单吲哚化合物FGFC2作用于血小板的异同。方法：从新鲜兔血收集血小板,调整反应体系血小板密度,以乙酰水杨酸为阳性对照,采用微量比浊法分析FGFC1和FGFC2对血小板聚集率的影响,用酶联免疫法测定FGFC1和FGFC2对血小板生理因子含量的变化。结果：FGFC1对ADP和AA诱导的血小板聚集具有抑制作用,最大抑制率分别达到42.58%±1.7%和47.82%±2.18%;FGFC2对ADP、AA和胶原诱导的血小板聚集均具有抑制作用,最大抑制率分别为50.12%±1.02%、45.28%±1.09%和50.28%±2.12%。FGFC1与FGFC2均能提升血小板内环磷酸腺苷含量,且FGFC2能明显降低血小板内血栓素A2含量。结论：海洋双吲哚纤溶活性化合物显著抑制血小板聚集,FGFC1通过影响血小板环磷酸腺苷的含量实现抑制血小板聚集,FGFC2可能通过不止一种途径抑制血小板聚集。吲哚化合物抑制血小板聚集与分子结构密切相关。     

Activation and inhibition of 3H-strychnine binding to the glycine receptor by Eccles' anions: modulatory effects of cations

The ammonium salts of Eccles' anions are inhibitors of 3H-strychnine binding. By contrast, the binding is activated by the sodium salts of these anions. This activation is due to an increase in the affinity for 3H-strychnine. Pretreatment of the membranes with acetic anhydride abolishes the effect of sodium salt, whereas ammonium salts remain unaffected. In the presence of chloride the inhibitory effect of ammonium predominates over the effect of sodium. These results suggest that the effect of Eccles' anions is profoundly modified by their counter-ions and that Na+ and ammonium are acting through distinct sites on the glycine receptor.     

海洋双吲哚化合物溶解大鼠脑微血栓的纤溶作用

目的 检测海洋双吲哚生物碱FGFC1对大鼠脑微血栓的纤溶作用。方法 静脉注射异硫氰酸荧光素-纤维蛋白诱导大鼠脑微血栓形成，低场核磁共振血栓成像和组织切片评价脑微血栓动物模型构建；颈静脉注射给药FGFC1，荧光比色法检测大鼠血浆荧光强度，ELISA方法检测纤维蛋白降解产物和纤溶酶原活性。结果 低场核磁共振血栓成像和HE染色组织切片显示异硫氰酸荧光素-纤维蛋白诱导大鼠脑部密度增强和脑血管管壁增厚；冷冻组织切片显示脑血管存在荧光亮斑；血浆荧光强度显示2 h时异硫氰酸荧光素-纤维蛋白诱导大鼠脑微血栓形成；当FGFC1给药剂量为5 mg/kg时，给药后2 h大鼠血浆FDP、D-D及PLG活性分别为595.24 ng/mL、5.70 ng/mL和86.98 IU/L，与空白对照组差异显著。结论 异硫氰酸荧光素-纤维蛋白诱导大鼠形成脑微血栓模型，FGFC1能够增强脑微血栓动物模型的纤溶活性，实现脑微血栓溶解；海洋纤溶化合物FGFC1具有发展为溶解脑微血栓药物的潜力。     

Effect of some selected salts and non-ionic surfactants on the antimicrobial activity of nalidixic acid

The effect of different concentrations of some selected salts, namely, sodium chloride, potassium chloride, ammonium chloride, monosodium dihydrogen phosphate, calcium chloride, dibasic sodium phosphate, sodium sulphate, aluminium chloride and sodium citrate on the antimicrobial activity of nalidixic acid was investigated. It was found that all the salts tested, except aluminium chloride and sodium citrate, exert no antimicrobial activity. The effect of 10% non-ionic surface active agents, namely, Myrj 51, 52, 59, Brij 35, 58, 98, Tween 20, 40, 60, and 80 on the antimicrobial activity of nalidixic acid was studied. The results indicated that the activity of nalidixic acid was decreased in the presence of these surfactants. Furthermore, the effect of different concentrations of sodium chloride on the antimicrobial activity of nalidixic acid-surfactants systems was reported.     

高效液相色谱法测定美敏伪麻口服溶液中苯甲酸钠的含量

目的建立HPLC法测定美敏伪麻口服溶液中苯甲酸钠的含量。方法采用C18色谱柱,检测波长为230 nm。以0.02 mol·L-1醋酸铵溶液-甲醇(95:5)为流动相A,甲醇为流动相B,梯度洗脱。结果该色谱条件下,苯甲酸钠与样品中其他成分分离很好,苯甲酸钠在36.59¹09.8μg·mL-1与峰面积线性关系良好。低、中、高浓度平均回收率分别为100.2%、100.1%、100.3%,RSD分别为0.1%、0.4%、0.2%。结论该法操作简单、准确、重现性好,可作为美敏伪麻口服溶液中苯甲酸钠的质控手段。     

Improvement of cardiovascular effects of metoprolol by replacement of common salt with a potassium- and magnesium-enriched salt alternative.

1. The influence of sodium chloride (NaCl)-enrichment of the diet (6% of the dry weight) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of the beta 1-adrenoceptor blocking drug, metoprolol, was studied in stroke-prone spontaneously hypertensive rats. 2. Increased dietary sodium chloride intake produced a marked rise in blood pressure and induced left ventricular and renal hypertrophy. By contrast, the salt alternative did not increase blood pressure and caused remarkably less cardiac and renal hypertrophy than did sodium chloride. 3. Metoprolol treatment at a daily dose of 250 mg kg-1 lowered blood pressure and decreased left ventricular hypertrophy index during the control diet. Sodium chloride-enrichment blocked the antihypertensive effect of metoprolol, while a partial protective effect on left ventricular and renal hypertrophy persisted. In the presence of the salt alternative-enrichment both at the level of 6% and 10.5% (corresponding to a NaCl level of 6%), metoprolol was fully able to exert its beneficial cardiovascular and renal effects. 4. Both salt supplementations, irrespective of metoprolol treatment, induced a 3 to 4 fold increase in the urinary excretion of calcium. There was a linear correlation between the urinary excretions of sodium and calcium. The urinary excretion of magnesium rose by 90% and that of potassium by 110% in the salt alternative group. 6. Our findings suggest that replacement of common salt by a potassium-, and magnesium-enriched salt alternative in the diet produces beneficial cardiovascular effects and improves the antihypertensive efficacy of metoprolol in stroke-prone spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stabilization of Sulfamerazine Suspensions by Xanthan Gum

Suspensions of sulfamerazine (10%) containing 0.2% docusate sodium were deflocculated because of repulsion between the negatively charged particles. Flocculation was induced by salts or by xanthan gum, which is anionic, in the presence of salts at concentrations below those at which salt flocculation resulted. The amount of gum necessary to produce a flocculated system was lower the higher the concentration of salt present. Calcium chloride and magnesium chloride were considerably more effective in this regard than sodium chloride. Gum flocculation produced aggregates with fewer particles and weaker bonding forces than did salt flocculation. The sedimentation rate of the suspensions decreased 5 to 10 times for each 0.1% increase in the gum concentration.     

Diclofenac salts. III. Alkaline and earth alkaline salts

Diclofenac salts containing the alkaline and two earth alkaline cations have been prepared and characterized by scanning electron microscopy (SEM) and EDAX spectroscopy; and by thermal and thermogravimetric analysis (TGA): all of them crystallize as hydrate when precipitated from water. The salts dehydrate at room temperature and more easily on heating, but recovery the hydration, when placed in a humid environment. X-ray diffraction spectra suggest that on dehydration new peaks appear on diffractograms and the lattice of the salts partially looses crystallinity. This phenomenon is readily visible in the case of the calcium and magnesium salts, whose thermograms display a crystallization exotherm, before melting or decomposing at temperatures near or above 200 degrees C; these last salts appear to form solvates, when prepared from methanol. The thermogram of each salt shows a complex endotherm of dehydration about 100 degrees C; the calcium salt displays two endotherms, well separated at about 120 and 160 degrees C, which disappear after prolonged heating. Decomposition exotherms, before or soon after the melting, appear below 300 degrees C. The ammonium salt is thermally unstable and, when heated to start dehydration, dissociates and leaves acidic diclofenac.     

Functional group contribution of bile salt molecules to partitioning of a quaternary ammonium N,N-dimethyl derivative of propranolol

A quaternary ammonium N,N-dimethyl derivative of propranolol was extracted from pH 7.4 phosphate buffer into 1-octanol as ion-pairs with 12 different bile salts. The binding number, n, and the extraction constant, Ke, were determined. To obtain group contribution values of the bile salt molecule from the ion-pair extraction data, multiple linear regression analysis by the Free-Wilson technique was applied. The results showed that the fundamental premise of the functional group's contribution to the ion-pair extraction is valid. The functional groups of counterions contribute to the partitioning of the ammonium compound independently and additively in this system.     

Analysis of steroids. Part 45: Analytical investigation of pipecuronium bromide (Arduan)]

The following methods are described for the analytical investigation of pipecuronium bromide. 1. HPLC method. Of the several systems tried for the separation and quantification of impurities and degradation products the best results were obtained using silica as the stationary phase and 43:43:14 mixture of methanol, acetonitrile and concentrated aqueous ammonia containing 0.1 mole/l each of ammonium chloride and ammonium carbonate as the eluent. The validation of this method is presented. The above described aggressive eluent can be successfully replaced by an ion-pairing system using silica as the stationary phase and 96:4 mixture of acetonitrile and water containing 0.1 mole/l sodium perchlorate as the eluent. 2. Thin-layer chromatography. TLC systems are described for the separation and densitometric quantification of the impurities and degradation products of pipecuronium bromide. 3. Spectrophotometry. Two methods are described. The ester groups of the molecule can be determined by the iron(III)-hydroxamate method while for the ion-pair extraction of the quaternary ammonium steroid picric acid or bromthymol blue are used as the reagents. 4. Titrimetry. In addition to the titration with acetous perchloric acid for the assay of the bulk material a microtitration method is described for the determination of pipecuronium bromide in individual lyophylized ampoules (potentiometric titration with 0.1 M silver nitrate).