雷公藤叶中二萜化合物的研究

从雷公藤(Tripterygium wilfordii)叶中分离出九个二萜化合物,经物理常数测定、化学反应、以及波谱数据分析,分别鉴定为雷公藤内酯酮(triptonide,1)、雷公藤内酯醇(triptolide,2)、雷公藤内酯二醇(tripdiolide,3);雷醇内酯(triptolidenol,4)、16-羟基雷公藤内酯醇(16-hydroxytriptolide,5)、雷公藤氯内酯醇(tripehlorolide,6)、雷藤内酯三醇(triptriolide,7),以及新化合物雷公藤内酯二醇酮(tripdiotolnide,8)和13,14-环氧9,11,12-三羟雷公藤内酯(13,14-epoxide 9,11,12-trihydroxytriptolide,9)。新化合物的生物活性正在研究。     

雷公藤内酯醇的结构修饰

为降低雷公藤内酯醇的毒性,寻找高效低毒的抗炎免疫化合物,对雷公藤内酯醇(trip-tolide,1)的结构进行了修饰,合成了九个雷公藤内酯醇衍生物。初步活性测定显示雷公藤氯内酯(tri-pchlorolide,2)和雷公藤溴内酯醇(tripbromolide,3)的免疫抑制活性与雷公藤内酯醇近似,但毒性有所降低。其他化合物的活性大大低于雷公藤内酯醇。     

昆明山海棠雄性抗生育成分的研究

昆明山海棠茎皮乙醇提取物中雄性抗生育活性成分的分离，显示氯仿部分及正丁醇部分为活性部分。用硅胶柱对这两部分进一步分离后，得到雷藤素乙（Ⅰ）、雷藤素甲（Ⅱ）、雷酚二萜酸（Ⅲ）、雷酚萜醇（Ⅳ）、3－oxo-olean-12-en-29-oicacid(Ⅴ）、齐墩果酸（Ⅵ）、3β，22α-dihydroxy-△^12-oleanen-29-oic acid(Ⅶ）、3－乙酰氧基齐墩果酸（Ⅷ）、雷公藤内酯甲（Ⅸ）、雷公藤次硷（Ⅹ）、胡萝卜甙（Ⅺ）、β－谷甾醇（Ⅻ）、1－表儿茶素（ⅩⅢ）及富马酸（ⅩⅣ）。其中3－oxo-olean-12-en-29-oic acid，齐墩果酸及富马酸为首次从雷公藤属植物中发现。雷藤素乙。雷酚萜醇，3－β，22α-dihydroxy-△^12-oleanen-29-oic acid及胡萝卜甙为首次从昆明山海棠中分离得到。药理筛选显示雷藤素乙及雷藤素甲对于雄性大鼠具有可逆性雄性抗生育活性，其有效剂量分别为每天200及30μg/kg。     

雷公藤多苷片中雷公藤总内酯及雷公藤内酯醇的测定

建立雷公藤多苷片中雷公滕总内酯及雷公藤内酯醇的含量测定方法。方法:采用比色法,以3,5-二硝基苯甲酸显色,于540 nm 波长处测定吸收度,测得雷公藤总内酯含量;另外采用高效液相色谱法,使用 ODS 柱(4.6 mm×250 mm,5μm),流动相 A 为甲醇,流动相 B 为甲醇-0.01mol·L~(-1)磷酸二氢钾水溶液(20∶80),采用梯度洗脱,于218 nm 处检测,测定雷公滕内酯醇的含量。结果:以比色法测定雷公藤总内酯(以雷公藤内酯醇计),浓度在8～40mg·L~(-1)范围内呈现良好的线性关系(r=0.9998),平均回收率(n=9)为100.6%;以高效液相色谱法测定雷公藤内酯醇,浓度在10～100 mg·L~(-1)范围内线性关系良好(r=0.9999),平均回收率(n=9)为99.6%。测得市售雷公藤多苷片中雷公藤总内酯含量在0.061%～0.363%范围内,雷公滕内酯醇含量在0.002%～0.200%范围内。结论:两方法均准确可靠、耐用性良好,可用于雷公藤多苷片质量分析控制。市售雷公藤多苷片中雷公藤总内酯及雷公藤内酯醇含量差异较大,应该加强其质量控制、保障用药安全与有效。     

HPLC同时测定杜仲-川芎药对中的7种成分

目的 采用HPLC法同时测定杜仲-川芎药对中绿原酸、松脂醇二葡萄糖苷、阿魏酸、洋川芎内酯I、洋川芎内酯H、洋川芎内酯A、藁本内酯等7种成分的含量。方法 采用Agilent Eclipse XDB-C₁₈色谱柱(250 mm×4.6 mm, 5μm),流动相为乙腈-0.1%磷酸水,检测波长326 nm(绿原酸、阿魏酸、藁本内酯)、276 nm(松脂醇二葡萄糖苷、洋川芎内酯I、洋川芎内酯H、洋川芎内酯A),进样量10μL。结果 绿原酸、松脂醇二葡萄糖苷、阿魏酸、洋川芎内酯I、洋川芎内酯H、洋川芎内酯A、藁本内酯的线性范围分别为5.160～258.0、6.624～331.2、3.490～174.5、1.522～76.10、0.3212～16.06、25.44～1.277×10³、21.98～1.099×10³μg·mL^-1(r>0.999);平均加样回收率为96.73%～103.09%,RSD为0.68%～2.6%(n=6)。结论 所用方法高效、便捷、准确、稳定,可为杜仲-川芎药对的质量控制提供参考...     

昆明山海棠化学成分研究

从昆明山海棠(Tripterygium hypoglaucum (Lévl.)Hutch)根中分得三个单体,经光谱分析鉴定晶1为已知物雷藤二萜酸(triptoditerpenic acid),晶2和晶3为新二萜化合物,分别命名为雷藤二萜酸B(triptoditerpenic acid B)和山海棠二萜内酯A(hypodiolide A)。     

高含量黄酮甙和银杏内酯、低含量烷基酚的银杏叶浸膏

一种新的银杏叶浸膏,几无烷基酚,但却有高含量黄酮甙并含叶中原已存在的大多数的银杏内酯和白果内酯。浸膏含20％～30％(重量)(最好为22％～26％)的黄酮甙,2.5％～4.6％(重量)的总银杏内酯(银杏内酯A、B、C和J),2.0％～4.0％(重量)的白果内酯。烷基酚少于10μg/ml(尤其少     

由γ-氯代乙酰丁内酯水解缩合制备硫代硫胺

硫代硫胺(简称SB_1)为生产维生素B_1(简称VB_1)的重要中间体。我国自1958年生产VB_1以来,合成SB_1的噻唑环系采取由甲基呋喃至氯代乙酰丙醇乙酸酯的“氯酯”路线,该路线因存在较多缺点,1977年我厂改用由乙酰丁内酯至氯代乙酰丙醇的“氯醇”路线,本法在各方面虽远优于“氯酯”路线,但仍存在下列一些问题,1.反应体积大;2.酸碱和甲醇耗用多;3.氯醇配比高;4.劳动条件差等。为此,1982年我们又进行了研究改革。由氯代乙酰丁内酯开环制备氯醇的反应式如下:     

不同栽培模式的银杏叶在不同生长季节中总黄酮醇苷和总内酯的含量变化

目的:探索银杏叶的最适宜的种植模式和采集季节。方法:采用高效液相色谱法分别测定银杏叶中总黄酮醇苷和总内酯的含量。总黄酮醇苷色谱条件为Waters Nova-Pak C_(18)柱(3.9mm×150mm,4μm),流动相:甲醇-0.5％磷酸水溶液(43:57),流速0.7mL·min~(-1),检测波长360 nm,柱温30℃,进样量20 μL,外标法计算含量;总内酯色谱条件为Waters Nova-PakC_(18)柱(3.9mm×150mm,4μm),流动相:甲醇-四氢呋喃-水(20:12:75),流速0.6mL·min~(-1),ELSD漂移管温度100℃,载气流量2.5 L·min~(-1),进样量20μL,以外标两点对数方程计算含量。结果:不同栽培模式的银杏叶总黄酮醇苷、总内酯含量随树龄的增加而下降,剪枝后两者的含量明显升高。在不同的生长季节,总黄酮醇苷在5月份含量最高,以后逐月下降;总内酯含量先升高,后下降。结论:这一变化规律为中药的规范化种植(GAP)提供了科学依据。     

HPLC定量分析制剂中雷公藤氯内酯醇含量

雷公藤氯内酯醇(T_4)是从雷公藤中分离得到的一个新化合物,但含量很低,因此进行了以雷公藤内酯醇(To)为原料合成T_4的研究。T_4具有较强的免疫抑制活性,且毒性低于雷公藤内酯醇,有希望开发成新药在临床应用。为了控制T_4制剂的质量,本文系统地研究了反相高效液相色谱法分离和测定T_4的条件,结果以甲醇-水(1:1)作流动相,能满意地分离和测定T_4的含量,最小检测量为10 ng,采用内标法定量,方法快速、准确。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.