近红外光谱技术用于川红活血胶囊提取过程的研究

目的用声光可调滤光器(AOTF)-近红外(NIR)光谱法在线分析中药新药川红活血胶囊提取过程中芍药苷的含量。方法在线收集川红活血胶囊提取样品,建立其芍药苷含量数据库,同时采集近红外光谱图谱,用偏最小二乘法(PLS1)分别建立近红外光谱与芍药苷含量数据之间的校正模型,并对在线过程中收集的预测集样品进行含量预测来验证所建模型。结果提取液近红外光谱与含量数据之间的校正模型相关系系数R2为0.992,外部样品预测模型相关系系数R2为0.995,外部样品预测相对偏差为4.25%;该方法用于芍药苷含量测定的精密度RSD为2.70%,稳定性RSD为2.07%,预测回收率为96.7%。结论 AOTF-NIR光谱技术用于川红活血胶囊提取液芍药苷含量分析快速、直接,并能实现现场分析。     

近红外光谱的数字化存储和应用的可行性探讨

目的对近红外光谱数字化存储和应用的可行性进行初步探讨。方法将样品近红外原始光谱转换为数字化形式并进行极值标准化处理,通过比较处理前后光谱的相似系数以及处理前后光谱所建立的定量分析模型的评价参数,初步考察了数字化存储后数据对于近红外定性、定量分析的影响。结果与结论数字化光谱保留4位有效数字即能满足近红外定性分析的需要,保留5位有效数字可满足近红外定量分析的需要。将近红外光谱进行数字化存储有一定的可行性。     

近红外光谱法测定盐酸吡格列酮片的含量

目的：利用近红外光谱建立快速测定盐酸吡格列酮片含量的方法。方法：用HPLC法测定100批盐酸吡格列酮片样品含量并采集各样品的近红外光谱数据,从中随机抽取80批样品组成校正集,另20批样品组成测试集,采用偏最小二乘法（PLS）建立定量模型,并预测测试集样品的盐酸吡格列酮含量。结果：所建立定量模型的交叉验证测定系数r^2为0．9903,交叉验证均方差（RMSPCV）为0．394;测试集样品的测定系数r^2为0．9875,预测均方差（RMSEP）为0．259,平均预测偏差0．18％。结论：本法操作简便、快速、环保,可用于盐酸吡格列酮片的快速定量分析。     

基于近红外光谱的阿立哌唑片溶出行为研究

目的 建立阿立哌唑片剂溶出行为近红外定量模型,预测片剂的溶出行为。方法 采集阿立哌唑片剂近红外光谱,进行溶出度试验,分别于3、6、9、12、15、30 min时测定每片的溶出度,采取卷积平滑方法预处理波段4 000.00～4 396.90 cm^-1和5 326.43～12 000.00 cm^-1的近红外光谱,以偏最小二乘法建立溶出行为模型。结果 不同时间点的校正均方根误差(RMSEC)和预测均方根误差(RMSEP)均在8%以下,不同时间点校正相关系数(R_C)和预测相关系数(R_P)均在0.95以上(6 min的相关系数除外),近红外光谱和各时间点溶出度之间呈现出良好的相关性。结论 近红外光谱分析技术能够预测阿立哌唑片剂的溶出行为,为近红外光谱分析技术在线监测片剂质量奠定了理论基础。     

中成药胶囊剂假药近红外识别模型的研究简

目的运用近红外漫反射光谱技术,建立中成药胶囊剂假药的近红外识别模型。方法利用快检车车载近红外光谱系统采集样品的近红外光谱,运用OPUS软件对光谱进行预处理,采用定性测试方法建立近红外快速识别模型。结果模型的预测结果与实验室的测定结果一致。结论该模型可作为现场快速筛查中成药胶囊剂假冒产品的重要手段。     

近红外光谱相关系数法测定野木瓜片中异性有机物

目的:利用近红外特征谱段相关系数法对野木瓜片中是否含有异性有机物进行快速定性分析。方法:使用近红外光谱仪的光纤附件测定光谱,以不含有异性有机物的野木瓜片的近红外光谱为参照光谱,选择特定谱段,建立待测样品光谱与参照光谱在该谱段的相似系数阈值,定性判断待测样品是否含有异性有机物。结果:选定6022～5587 cm-1谱段为特征谱段,设定阈值为65%,用54个含异性有机物的样品进行验证,相关系数小于65%的有49个,占样品总量的90.74%。结论:此方法具有较好的预测能力,可用于药品检测车现场的快速筛查。     

不同产地大黄药材的近红外漫反射光谱法鉴别

目的:建立用近红外漫反射光谱鉴别不同产地大黄药材的新方法。方法:采集不同产地的大黄药材及其伪品的近红外漫反射光谱,分别用OPUS软件自带的聚类分析组件与第二军医大学药学院研发的近红外光谱-褶合变换-信息可视化-相似系数分析软件对其进行鉴别。结果:聚类分析的结果不甚理想,褶合变换分析得到正品与伪品大黄的相似系数<0.68,而正品大黄药材之间的相似系数均>0.81,同产地的药材之间的相似系数均>0.92。结论:近红外光谱法简便、快速,结合褶合变换分析得到的相似系数能够准确鉴别正品、伪品以及不同产地的大黄药材,所得分析结果与经典的形态分类学鉴别方法一致。     

近红外漫反射光谱法快速判别注射用炎琥宁的冻干骨架结构

目的:建立快速判别注射用炎琥宁冻干骨架结构的对向传播人工神经网络(counter-propagation artificial neural net-work,CP-ANN)近红外漫反射光谱法。方法:采用配有积分球附件的Antaris II傅里叶变换近红外光谱仪测定注射用炎琥宁的近红外漫反射光谱;用TQ Analyst 8.0进行光谱处理及数据预处理;用注射用炎琥宁校正样品的近红外漫反射光谱数据、以Matlab 6.5建立未损与已损冻干骨架结构的CP-ANN判别模型,并对模型进行交叉验证;用所建CP-ANN模型预测注射用炎琥宁验证样品冻干骨架结构的完整性。结果:所建近红外漫反射光谱CP-ANN判别模型预测注射用炎琥宁冻干骨架结构的准确率为100.0%,且具有良好的可视化功能。结论:所建方法判断客观,无损、无污染,简便快速,可望用于冻干注射用制剂的生产过程质量控制或临床使用质量控制。     

近红外光谱法鉴别普伐他汀钠片及其原料药晶型的一致性研究

目的 建立全覆盖抽样的普伐他汀钠片的近红外光谱法一致性检验模型,考察制剂工艺的差别和原料药晶型的差异,通过稳健、准确、代表性强的近红外光谱一致性模型实现普伐他汀钠片的快速检验和筛查。方法 对评价性抽验抽取的5个企业中的4个共65批样品建立普伐他汀钠片近红外一致性检验模型,并对4个厂家的原料药的近红外光谱图进行比较。结果 建立了4个厂家普伐他汀钠片剂的近红外一致性模型,预测成功率均为100%;4种原料药和1种无定型粉末的近红外光谱图显示不同晶型光谱图具有差异。结论 近红外光谱法能够用于快速鉴别质量工艺稳定的普伐他汀钠片产品,对制剂工艺进行考察,并能够区分不同晶型的原料药。     

近红外光谱法快速分析硝酸甘油片的含量

目的:建立测定硝酸甘油片含量的近红外光谱(NIR)快速分析方法。方法:以全国不同企业生产的硝酸甘油片为分析对象,用光纤探头在12000~4000 cm-1光谱范围内测定近红外漫反射光谱;以校正均方差(RMSEC)和相关系数(R2)为指标,通过筛选,确定了用于建模的最优近红外波段和光谱预处理方法,建立了近红外光谱与HPLC分析值之间的校正模型,并以此预测了15个未知样本。定性鉴别方法为马氏距离与限定值相比较。结果:定量模型的浓度范围为0.552%~1.581%g.g-1,相对标准偏差小于8%,定性鉴别方法可将硝酸甘油片与其他硝酸酯类片剂及安慰剂相区别。结论:该方法快速、简便,具有一定的专属性,可用于药物的快速检验。     

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.