姜黄素-邻苯二酚共晶溶度积的研究

目的 以姜黄素为药物活性成分,邻苯二酚为共晶形成物,研究姜黄素-邻苯二酚共晶在不同溶剂（甲醇和乙酸乙酯）中和不同温度下形成的热力学。方法 通过固态研磨法制备姜黄素-邻苯二酚共晶,并用X射线衍射表征,测定其在不同溶剂（甲醇、乙酸乙酯）、不同温度下的溶解度,采用络合模型计算共晶的溶度积（K_sp）和络合常数（K₁₁）。结果 姜黄素-邻苯二酚共晶在甲醇溶剂中符合1：1溶液络合模型,随着温度的升高,K_sp逐渐增大,K₁₁逐渐减小。在乙酸乙酯溶剂中符合无溶液络合模型,K_sp随温度升高而逐渐增加。结论 比较共晶在2种溶剂中的溶度积,发现其在甲醇中容易络合。该热力学研究为姜黄素-邻苯二酚共晶的制备条件优化奠定了一定的理论和应用基础。     

正交试验法优选炙甘草汤壳聚糖絮凝纯化工艺

摘 要 目的： 优选炙甘草汤的壳聚糖絮凝纯化工艺。方法: 采用正交试验法,以提取液中人参皂苷Rg₁、Re、Rb₁的总含量及除杂率为评价指标,考察药液质量浓度、壳聚糖加入量、静置温度对纯化工艺的影响。 结果: 炙甘草汤壳聚糖絮凝纯化的最佳工艺为药液质量浓度0.25 g·mL^-1,静置温度25 ℃,壳聚糖加入量12 %。 结论:优选的壳聚糖絮凝纯化工艺除杂率高,指标性成分损失量少,为炙甘草汤的剂型改革提供参考     

三种方法提取生姜有效部位群并测定6-姜辣素含量

摘 要 目的:比较三种生姜的提取方法,优化生姜药材的提取工艺及工艺参数。方法: 建立反相高效液相色谱法测定生姜指标成分6-姜辣素的分析方法,比较水蒸气蒸馏法、超临界CO₂萃取法和乙醇渗漉法提取生姜的工艺。 结果:该6-姜辣素的含量测定方法稳定可靠;超临界CO₂萃取法和乙醇渗漉法提取率较高,超临界CO₂萃取物中6 姜辣素的含量显著高于水蒸气蒸馏法和乙醇渗漉法。结论: 三种方法中以超临界CO₂萃取法为提取生姜的最佳方法。     

星点设计-效应面法优化白鲜皮多糖硫酸酯化工艺及抗氧化活性

目的 利用星点设计-效应面法优化白鲜皮多糖（Dictamnus dasycarpus polysaccharide,DDP）硫酸酯化工艺,考察DDP修饰前后结构特征及抗氧化活性。方法 采用氯磺酸-吡啶法,以酯化试剂比例、酯化试剂与多糖溶液比例、反应温度、反应时间为自变量,硫酸根取代度（degree of substitution,DS）为因变量,对自变量各水平进行多元回归拟合,利用效应面法筛选最佳工艺并进行预测分析;采用红外光谱及扫描电镜观察其结构特点。测定硫酸酯化白鲜皮多糖（sulfated polysaccharides from Dictamnus dasycarpus,SDDP）对DPPH、OH·、O₂^-·清除能力,考察其抗氧化活性。结果 最佳工艺条件为酯化试剂比例1：4,酯化试剂与多糖溶液比例1：1,反应温度73℃,反应时间5 h。红外光谱显示SDDP在820 cm^-1和1 254 cm^-1附近出现C-O-S和S=O硫酸基特征吸收峰,表明DDP修饰成功;扫描电镜显示SDDP表面粗糙,排列紧密,且块状体积明显小于DDP;DDP和SDDP都有清除DPPH、OH·和O₂^-·能力,且SDDP对DPPH、OH·和O₂^-·清除率强于DDP。结论 星点设计-效应面法优化DDP硫酸酯化工艺方法简便且预测性良好,DDP经硫酸酯化后,抗氧化活性有所提高。     

正交设计法优化新型氮唑类抗真菌化合物关键中间体的合成工艺

目的 优化新型氮唑类抗真菌化合物关键中间体的合成工艺。方法 采用正交设计法,重点考察反应温度、投料比、反应时间及溶剂4个因素对收率的影响。结果 反应温度对反应收率的影响最为显著,其次是反应时间;投料比及溶剂对收率影响不明显。结论 新工艺的收率可达50%左右,反应杂质少,后处理简便。     

响应面法优化西罗莫司胶束及其促小肠吸收作用

目的 制备和优化西罗莫司（sirolimus，SRL）聚合物胶束，考察其对大鼠在体肠吸收动力学的影响。方法 以去氧胆酸修饰的壳聚糖（deoxycholic acid grafted chitosan，CS-DCA）为载体，采用溶剂蒸发法制备SRL CS-DCA胶束。以包封率、载药量、粒径和电位作为考察指标，结合星点设计-效应面法优化处方。建立大鼠在体单向肠灌流模型，并通过肠腔有效吸收系数（P_eff）、吸收速率常数（K_a）和药物吸收剂量分数（f_a）研究不同浓度SRL CS-DCA的肠吸收特性。结果 SRL CS-DCA最优处方：载体浓度（CS-DCA）为10 mg·mL^-1，药物与载体质量比为20%，该条件下制备得到的SRL CS-DCA带正电荷（37.0±2.7）mV，粒径（182.2±5.7）nm，包封率>90%，载药量（15.8±0.5）%。SRL CS-DCA经大鼠全肠后，反映药物肠吸收程度的评价指标P_eff、K_a和f_a均较SRL有显著提高（P<0.05）；不同浓度的SRL CS-DCA在大鼠全肠段的P_eff、K_a、f_a值无显著性差异，提示胶束在10~100 μg·mL^-1吸收无浓度抑制，吸收特征为被动转运的线性动力学过程，推测其可能的吸收机制为被动扩散。结论 SRL制备成聚合物胶束后，对其在大鼠小肠的吸收具有明显的促进作用，从侧面证明SRL CS-DCA能有效改善SRL口服生物利用度。     

水溶性壳聚糖的制备及其降血脂作用

目的研究水溶性壳聚糖的制备工艺，并考察其降血脂效果。方法采用H₂O₂氧化法制备水溶性壳聚糖，采用灌胃给药方式考察相对黏度为1.1、1.8和3.0（50℃条件）的水溶性壳聚糖对小白鼠降血脂药效。结果平均分子量1000壳聚糖的制备工艺条件为：1%Hac为溶剂、壳聚糖浓度20 g/L、3%H₂O₂∶壳聚糖为0.5∶1、反应温度为60℃、反应时间为20 min。相对黏度为1.1、1.8和3.0的三种水溶性壳聚糖均能显著降低小鼠血浆的TCH水平，降幅可达26～30%。相对黏度1.1和3.0的壳聚糖能显著降低小鼠血浆的TG水平及MDA含量，降幅可分别达24～34%和38～40％。结论本工艺制备的三种不同黏度的壳聚糖具有较强的降脂药效，其降脂和抗氧化效果接近市售降脂良药软脉灵口服液。     

温经活血巴布剂中挥发油的提取工艺

目的 优选温经活血巴布剂中挥发油的超临界CO₂萃取工艺条件。方法 在单因素考察萃取温度、分离斧I温度、萃取压力、萃取时间对萃取得率、蛇床子素含量和异欧前胡素综合评分的基础上,正交设计优选萃取温度、萃取压力、萃取时间对所提挥发油综合评分的影响。结果 单因素实验中,对所提挥发油综合评分影响较大的因素为萃取温度,萃取压力和萃取时间,正交实验结果表明萃取温度、萃取压力对挥发油综合评分有显著影响,优选的最佳工艺为：萃取温度为55 ℃,萃取压力为30 MPa,萃取时间为2.0 h。结论 本实验优选的萃取工艺稳定可行,可用于该挥发油的提取制备。     

儿童静滴维生素K1注射液引起的17例药物不良反应分析

目的 通过探讨维生素K1注射液药物不良反应发生的影响因素及规律,为儿童安全、合理使用维生素K₁注射液提供依据。方法 通过对我院2012~2017年发生的17例维生素K₁注射液引起的不良反应病例进行统计分析。结果 维生素K1注射液发生药品不良反应与药物本身的质量、用药人群的生理特点及临床用药合理性等因素密切相关。结论 应加强维生素K₁注射液合理应用及管理,保证儿童用药安全。     

马钱子碱与β-环糊精聚合物的包合平衡常数及热力学研究

摘 要 目的： 研究马钱子碱与β-环糊精聚合物(β-CDP)在不同温度,pH溶液中的包合作用及包合过程中的热力学参数变化。方法: 采用相溶解度法测定β-CDP对马钱子碱溶解度的影响,计算包合平衡常数(K_c)和包合热力学参数。结果: 在25℃,37℃,45℃时,包合平衡常数(K_c)分别为88.38,349.29,641.79 L·moL^-1,在pH为4,6.8,10时,K_c分别为490.66,111.85,58.86 L·moL^-1。马钱子碱的溶解度随β-环糊精聚合物浓度的增加呈线性增加,其相溶解度曲线均为AL型,在酸性条件下β-CDP包合常数及增溶作用较大。结论: β-CDP对马钱子碱有较好地增溶作用,可形成摩尔比为1∶1的稳定包合物,包合过程可自发进行(ΔG<0) ,温度的升高,pH的降低有利于包合物的形成。     

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.

     

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.     

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.     

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.