甘草酸磷脂复合物自乳化制剂处方筛选

目的 对甘草酸磷脂复合物自乳化制剂(self-emulsifying drug delivery system,SEDDS)进行处方筛选及制备。方法 用溶解性实验,处方配伍实验和伪三元相图等方法进行甘草酸磷脂复合物SEDDS制备研究,优选乳化剂,油相和助乳化剂;确定处方组分比例,考察处方自乳化效率。结果 最佳甘草酸磷脂复合物SEDDS处方为Labrafil 1944 cs∶Cremophor EL35∶Transcutol HP =45∶40∶15,处方载药量为27.3%;该处方能形成具有乳光透明乳液,粒度分布均匀。结论 该方法可成功制备甘草酸磷脂复合物自乳化制剂。     

甘草酸磷脂复合物自乳化胶囊与肠溶胶囊的药动学比较

目的以市售甘草酸二铵肠溶胶囊为参比制剂,考察自制甘草酸磷脂复合物自乳化胶囊在Beagle犬体内的相对生物利用度。方法Beagle犬6只,自身交叉对照、单剂量灌胃甘草酸磷脂复合物自乳化胶囊或市售肠溶胶囊。采用HPLC测定血浆中的甘草酸浓度,DAS2．0程序拟合药代动力学数据。结果参比制剂和受试制剂主要的药动学参数：Tmax分别为（6．00±0．000）h,（2．917±0．585）h;Cmax分别为（12．756±1．075）mg·L^-1,（17．75±1．604）mg·L-1;AUC0-t分别为（150．89±22．850）mg·h·L-1,（211．196±40．880）mg·h·L^-1;AUC分别为（159．39±21．862）mg·h·L^-1,（221．287±2．164）mg·h·L^-1,甘草酸磷脂复合物自乳化制剂相对生物利用度（F％）为139．76％。结论Beagle犬体内甘草酸的药动学规律均符合一级吸收二室模型,与市售胶囊剂相比,自乳化制剂的Cmax、AUC0-t,AUC0-∞均高于肠溶胶囊,表明自乳化制剂能显著提高药物的生物利用度,初步达到了设计要求。     

甘草酸二铵磷脂复合物注射液的初步稳定性研究

目的制备合适的甘草酸二铵磷脂复合物注射液,并考察其初步稳定性。方法以粒径、过氧化值、pH为指标,分别考察了不同种类溶媒和pH值对注射液稳定性的影响。通过影响因素实验的结果确定最佳处方,并对最适处方进行加速实验。结果以5%葡萄糖注射液为溶媒的处方在高温60℃和强度4 500 Lx光照下放置10 d理化性质没有发生明显变化,且初步加速实验也显示出良好的稳定性。结论甘草酸二铵磷脂复合物葡萄糖注射液质量稳定,粒径符合肝脏靶向性要求。     

靛玉红及其磷脂复合物和自乳化释药系统在犬体内的药动学

目的:考察靛玉红及其磷脂复合物和自乳化释药系统在犬体内的药动学过程。方法:采用三周期交叉试验设计法,取6条健康beagle犬随机分成3组,分别服用剂量为100mg的靛玉红片、靛玉红磷脂复合物和靛玉红自乳化释药系统,用高效液相色谱(HPLC)法测定靛玉红的血药浓度,利用3P97软件包和统计矩方法计算主要药动学参数和相对生物利用度。结果:以靛玉红片为对照,靛玉红磷脂复合物和自乳化释药系统的相对生物利用度分别为(157±s 10)%和(162±16)%。结论:磷脂复合物和自乳化释药系统有利于改善靛玉红口服生物利用度。     

银杏黄酮磷脂复合物自乳化释药系统处方研究

目的:优化银杏黄酮磷脂复合物自乳化释药系统处方。方法:以银杏黄酮磷脂复合物在不同种类及比例的油相、表面活性剂中的溶解度为考察指标,筛选自乳化释药系统处方。结果:该处方制备的银杏黄酮磷脂复合物自乳化软胶囊能够迅速溶解并乳化,在蒸馏水、pH6.8磷酸缓冲液和0.1mol/L的HCl中,该系统中的银杏黄酮在45分钟内的溶出度均在80%以上。结论:该自乳化释药系统大大提高了银杏黄酮在水中的溶出度。     

水飞蓟宾磷脂复合物自微乳给药系统研究

目的研制水飞蓟宾（SLB）磷脂复合物自微乳化胶囊并对其进行体外评价。方法通过单因素考察结合正交设计将SLB制成磷脂复合物,测定了该复合物的溶解度和油水分配系数,进一步制成自微乳给药系统。结果 SLB磷脂复合物的最佳工艺条件为,反应温度50℃,反应时间2 h,比例1∶2。按此最佳工艺条件制备SLB磷脂复合物,复合率为100%,其溶解度和油水分配系数分别为126.3μg.mL-1,166.64,其最佳自微乳给药系统（PMC）组成及比例为,复合物∶油酸乙酯∶吐温80∶丙二醇=12∶30∶45∶13。按最佳处方制备的SLB磷脂复合物-PMC在人工胃液中36 min内累积溶出百分率已达到80%。结论将水飞蓟宾制成磷脂复合物自微乳化胶囊能显著提高其体外溶出度。     

酮洛芬自乳化制剂处方及化学稳定性研究

目的建立酮洛芬自乳化制剂处方 ,并考察其稳定性。方法通过溶解度实验和三元相图的建立 ,筛选酮洛芬自乳化制剂处方。用HPLC法测定处方经高低温循环和光照加速实验前后药物的含量 ,考察其化学稳定性。结果酮洛芬自乳化制剂处方中油相、表面活性剂和助表面活性剂分别为油酸乙酯、Tween 80和乙二醇单乙基醚 (Transcutol)。处方经高低温循环后酮洛芬平均含量由 99 8% (w)变为 99 0 % (w) ,光照 5d和 10d后 ,平均含量分别降为 85 7% (w )和 6 8 7%(w )。结论酮洛芬自乳化制剂处方比例为酮洛芬 油酸乙酯 Tween 80 Transcutol(w∶w∶w∶w =5 0∶4 0 0∶4 3 5 0∶11 5 )。制剂对热稳定 ,对光不稳定 ,需避光保存     

磷脂复合物一自乳化释药系统研究进展

磷脂复合物一自乳化释药系统是一种新型的释药系统,它结合了磷脂复合物与自乳化技术,能发挥二者的协同作用,提高生物利用度。磷脂复合物一自乳化释药系统为中药剂型的研究开辟了一条新的道路。该剂型具有广阔的市场前景,现将有关此类释药系统的研究情况做一介绍。     

均匀设计法优选鼻窦炎口服液的澄清工艺

目的优选鼻窦炎口服液的最佳澄清工艺条件。方法采用U_8(8~3×4)均匀设计试验法,以黄芩苷含量和沉渣回收量为指标,选取浓缩液相对密度、冷沉时间、pH值、离心次数为考察因素,优选鼻窦炎口服液的澄清工艺。结果最佳澄清工艺条件为浓缩液相对密度为1.18(25℃),冷沉时间为72 h,pH值为6.1,离心次数为2。结论该优选工艺合理、稳定、可行,可为鼻窦炎口服液的生产提供依据。     

磷脂复合物-自乳化释药系统研究进展

磷脂复合物-自乳化释药系统是一种新型的释药系统,它结合了磷脂复合物与自乳化技术,能发挥二者的协同作用,提高生物利用度。磷脂复合物-自乳化释药系统为中药剂型的研究开辟了一条新的道路。该剂型具有广阔的市场前景,现将有关此类释药系统的研究情况做一介绍。     

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.