酮咯酸氨丁三醇海藻酸钠-壳聚糖微囊的制备

以微囊的载药量和包封率为指标,采用均匀设计,结合非线性规划法优化酮咯酸氨丁三醇海藻酸钠-壳聚糖微囊的制备工艺.结果表明,按优化条件制得的微囊包封率90%,载药量44%,在水中的释药行为符合Higuchi方程.     

阿司匹林壳聚糖-海藻酸钠微囊处方优化与释药机制研究

目的:制备阿司匹林壳聚糖-海藻酸钠微囊(ACSPM),并研究其处方优化与释药机制。方法:设计正交试验,以包封率为指标优化ACSPM处方并制备微囊,测定其释放度并通过释放动力学模型方程拟合探讨其释药机制。结果:所得微囊大小及含量均匀,最优处方中海藻酸钠浓度、壳聚糖浓度、海藻酸钠与阿司匹林比例分别为3.0%、1.0%、1∶4,体外释放符合Higuchi方程和Peppas方程。结论:该微囊制备工艺方法简单,释药机制以药物扩散为主兼有骨架溶蚀的non-Fickian过程。     

对乙酰氨基酚/阿拉伯胶-壳聚糖多层微囊的制备及其体外释药研究

目的:制备对乙酰氨基酚多层微囊并考察其体外释药性能和机制。方法:以阿拉伯胶和壳聚糖为囊材,以戊二醛为交联剂,使用溶液干燥法(复合乳液法)制备载药(对乙酰氨基酚)多层(阿拉伯胶-壳聚糖-阿拉伯胶-壳聚糖)微囊。通过正交试验,以阿拉伯胶溶液-二氯甲烷体积比(A)、壳聚糖用量(B)、戊二醛-成壳材料总量比例(C)为因素,包封率为指标,优选制备工艺。通过测定其在盐酸溶液中的体外累积释药率并进行释放动力学模型拟合分析其释药机制。结果:最佳工艺条件为A4:3、B0.6g、C1:3。所制备的多层微囊球形完整、光滑,囊壁较厚;突释效果不明显,药物在12h内全部释放,其体外释药机制符合Ritger-Peppas模型。结论:所制载药多层微囊突释效应小、缓释效果较好。     

低分子肝素微囊的制备及其缓释性

目的：研制低分子肝素缓释微囊。方法“以乙基纤维素为囊材，正交实验设计优选制备工艺，用液中干燥法制备低分子肝素微囊，以光学显微镜观察其形态及大小分布，体外溶出试验研究其缓释性。结果：所得微囊颗粒圆整，粒径在100－800μm，载药量为56.3%,8h累积释放百分率为86.6%。结论：所制得微囊具有良好的缓释效果，有良好的应用开发前景。     

普罗布考微囊的制备与性质考察

目的:研究普罗布考微囊的制备工艺,考察其体外释药特性.方法:用复凝聚法制备普罗布考微囊,以包封率为指标,用正交试验设计法对微囊的制备工艺进行研究,对其形态、体外释药特点等进行研究.结果:当囊心与囊材比为1:3、搅拌速率为200r/min、成囊温度为60℃时,制得的普罗布考微囊囊形圆整光滑,囊壁清晰,粒径均匀,平均包封率可高达74.57%,载药量平均为17.93%,囊径为35~95μm,24h累积释药量93.61%.结论:制备的普罗布考微囊工艺简单、可靠,具有缓释效果.     

酮咯酸氨丁三醇微囊的研究

目的制备酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊，对其体外释药特性进行考察。方法采用滴液法制备微囊，以均匀设计优化制备工艺，溶出度测定法考察微囊体外释药特性。结果80％微囊粒径在200-250μm，微囊表面光滑圆整无粘连，包封率达90．56％，载药量达43．65％；微囊在人工胃液和蒸馏水中的释药规律符合Higuchi方程。结论酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊在人工胃液和蒸馏水中具有缓释作用。     

萘普生缓释微囊的制备及其体外释药研究

目的 对以壳聚糖和海藻酸钠为囊材,通过复凝聚法将萘普生微囊化的制备工艺和体外释药进行研究.方法 以微囊的药物包封率为制备工艺优化指标,得出成囊的最佳制备工艺条件.结果 最佳工艺条件为:搅拌速度500 r·min-1,pH4.0,壳聚糖浓度3%,反应温度50℃.结论 以最佳制备工艺条件制备了可生物相容,自然降解无毒的载药微囊,重现性好,工艺稳定,同时体外溶出实验表明,该微囊具有较好的缓释作用.     

喷雾干燥法制备丹酚酸壳聚糖微囊

目的以壳聚糖为载体制备丹酚酸微囊,并对其体外释药模式进行研究。方法以收率和载药量为指标,考察处方及工艺因素对微囊的影响,并对处方和工艺进行优化。结果壳聚糖质量浓度1.5%,丹酚酸与壳聚糖的质量比1∶3,进风温度190℃,蠕动泵速度300mL.h-1,所制得的微囊表面圆整,载药量为25.99%,收率为51.88%,包封率为86.21%,平均粒径为105.6nm。体外具有一定的缓释特性,在0～240min内拟合一级释药模型方程ln(1-Q)=-0.236 9 t+4.591 7,r=0.920 3。结论采用喷雾干燥法制得的丹酚酸微囊,收率和载药量较高,制备工艺简单,可望成为实现中药微球工业化的有效方法。     

紫草素微囊的固化机制与性能

目的考察单宁酸和氯化钙作为固化剂对微囊的成囊性及体外释药特征的影响,并对其固化机制进行探讨。方法以明胶和海藻酸钠为壁材,单宁酸和氯化钙作为固化剂,采用复凝聚法制备紫草素微囊;用扫描电子显微镜、激光粒径测试仪、红外光谱仪等手段研究微囊微球的形态结构;采用转篮法评价微囊的体外释药特性。结果制备得到了球形良好、缓释效果良好的单宁酸微囊,单宁酸和氯化钙制备的微囊包封率分别为90.34%±1.36%和69.89%±1.28%;平均粒径为241.7±6.94和278.1±4.74 nm,Zeta电位为-27.3±3.6和-24.7±3.2 mV;红外图谱显示单宁酸固化的微囊可以将紫草素包裹得更完全,使紫草素的特征峰完全消失,而氯化钙固化的微囊只能包裹部分紫草素,不能使其特征峰消失。体外释放实验结果表明,单宁酸作固化剂制备的微囊在12 h时释药率达到96.81%;而以氯化钙作固化剂制备的微囊,在6 h时释药率达到97.57%。结论固化剂的选择对微囊的成囊有较大的影响,为微囊固化剂的研究奠定了基础。     

诺氟沙星微囊的研制

研制溶剂 -非溶剂法制备诺氟沙星微囊以乙基纤维素为囊材的最适溶剂 -非溶剂系统的组成 .采用 4种不同的溶剂 -非溶剂系统用同一工艺条件制备 ,计算包囊率和收率 ,转篮法测定释药特性 .二氯甲烷 -正己烷对于制备诺氟沙星微囊较适宜 ,包囊率在 4种溶剂 -非溶剂系统中最高达 90 .90 % ,收率为 87.2 7% ,且缓释作用最好 .该系统有机溶剂沸点较低 ,利于除去微囊产品中的有机溶剂 ,减少对机体的毒性 .以二氯甲烷 -正己烷为溶剂 -非溶剂制备诺氟沙星微囊包囊率大 ,收率高 ,适于工业化生产     

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.