不同透皮吸收促进剂对复方水杨酸凝胶透皮作用的影响

目的：探讨不同的促进剂对复方水杨酸凝胶透皮吸收的影响。方法：配制含不同促进剂的复方水杨酸凝胶，采用简单扩散小室装置，用紫外分光光度法测定不同处方凝胶剂中水杨酸和苯甲酸的透皮吸收药量。结果：水杨酸和苯甲酸的累积透皮吸收百分率与时间呈线性关系。与不合吸收促进荆的凝胶比较，吸收促进剂对水杨酸和苯甲酸透皮吸收的影响为薄荷脑＋油酸〉薄荷脑〉薄荷脑＋月桂氮[艹卓]酮〉油酸〉不合促渗剂〉软膏剂〉月桂氮[艹卓]酮。结论：薄荷脑，油酸对复方水杨酸凝胶的透皮吸收有明显的促进作用，其中以薄荷脑＋油酸的作用最明显，单独使用月桂氮[艹卓]酮对复方水杨酸凝胶剂有抑制作用。     

月桂氮芯卓酮对青藤碱凝胶剂的透皮吸收作用

目的:考察不同浓度月桂氮(艹卓)酮(azone)对青藤碱凝胶透皮作用的影响,为青藤碱凝胶剂的处方筛选提供依据。方法:采用改良Franz扩散池,以离体大白鼠皮肤为透皮屏障,配制含不同浓度月桂氮(廿卓)酮的青藤碱凝胶,用HPLC法测定青藤碱的透皮吸收量,结果:青藤碱凝胶含2％azone时透皮吸收最好,其体外累积渗透量及促造速率最大。青藤碱凝胶剂的体外渗透药动学符合Higuchi方程。结论:选择2％azone作为青藤碱凝胶剂的促透剂。     

非洛地平-美托洛尔复方贴剂的透皮吸收促进剂优化

目的：优化复合透皮吸收促进剂，制备非洛地平-美托洛尔复方贴剂，并对其外观、物理特性、体外药物释放和经皮渗透性能进行综合评价。方法：以药物体外释放速率和稳态透皮速率为指标，通过正交设计试验考察桉叶油醇、月桂氮[艹卓]酮和丙二醇体系对贴剂质量的影响，优选最佳复合透皮吸收促进剂构成。结果：优选的透皮吸收促进剂最佳含量分别为桉叶油醇5％、月桂氮[艹卓]酮3％和丙二醇12%，以该促透体系制备的贴剂药物体外释放速率和稳态透皮速率高，外观和理化特性较佳，物理黏性适宜，各指标均达到预期设计要求。结论：桉叶油醇-月桂氮[艹卓]酮-丙二醇（5：3：12）复合体系对非洛地平和关托洛尔的协同促透作用显著，且稳定可靠，是非洛地平关托洛尔复方贴剂的优良透皮吸收促进剂。     

不同浓度的月桂氮(艹卓)酮对双氯芬酸钠凝胶剂透皮吸收的影响

目的通过动物离体透皮吸收试验,选择双氯芬酸钠凝胶剂中最佳浓度的月桂氮(艹卓)酮(氮酮,Azone)作为渗透促进剂.方法采用改良的Franz扩散装置,以离体鼠皮为屏障、生理盐水为接受介质,研究了不同浓度的月桂氮(艹卓)酮(0%、1%、2%、3%、5%Azone)对双氯芬酸钠凝胶剂透皮吸收的影响.结果双氯芬酸钠凝胶剂12h累积透皮释药百分率依次为38.42%、62.35%、72.80%、32.10%、55.36%.结论 Azone促进双氯芬酸钠凝胶剂透皮释药的最大浓度为2%,筛选出2%月桂氮(艹卓)酮作为促进剂,制备了具有良好经皮吸收性能的双氯芬酸钠凝胶剂.     

混合透皮促进剂对替硝唑凝胶透皮吸收作用的研究

目的：考察混合促进剂月桂氮苷卓酮和薄荷脑对替硝唑透皮吸收作用的影响。方法：采用改良 Ｆｒａｎｚ 直立式释放池,以离体小白鼠皮肤为透皮屏障,使用不同浓度的混合月桂氮苷卓酮和薄荷脑,测量替硝唑的透皮吸收量。结果：含０ ．５ ％ ,１ ．５ ％ ,２ ％ ,２ ．５ ％ 月桂氮苷卓酮和薄荷脑的替硝唑凝胶与不含月桂氮苷卓酮和薄荷脑的替硝唑凝胶间,其透皮吸收在２４ ｈ 后有显著差异（ Ｐ＜ ０ ．０５） 。含１ ％ 月桂氮苷卓酮和薄荷脑的替硝唑凝胶与不含月桂氮苷卓酮和薄荷脑的替硝唑凝胶间,其透皮吸收在２ ｈ 后则呈极显著差异（ Ｐ＜ ０ ．０１） 。结论：不同浓度的混合促进剂均可不同程度地促进替硝唑的透皮吸收效果,其中以１ ％ 月桂氮苷卓酮加１ ％ 薄荷脑组成的混合促进剂作用最显著。     

N-三甲基壳聚糖对哈西奈德软膏体外促透作用考察

目的：考察取代度为60％的N-三甲基壳聚糖（TMC60）对哈西奈德软膏体外透皮速率的影响。方法：将2％TMC60用于哈西奈德软膏中作为吸收促进剂，并以含2％月桂氮[艹卓]酮的哈西奈德软膏作为阳性对照，以不含任何促渗剂的哈西奈德软膏作为阴性对照，采用Franz扩散池法进行小白鼠离体皮肤渗透实验，HPLC法测定接受液中哈西奈德的含量，计算累积透过量Q，得出Qt回归方程及稳态渗透速率J。结果：哈西奈德线性范围为2．5～75mg·L^-1，回归方程为Y=0．1338＋4．4916X，r=0．9999；回收率为（100．0±0．9）％；日内精密度为1．26％；日间精密度为2．40％。月桂氮[艹卓]酮组和TMC60组的J分别为3．71，3．89（μg·m^-2·h^-1），两者差异无显著性（P＞0．05），而与阴性组相比差异均具有显著性（P＜0．05）。结论：2％TMC60对哈西奈德软膏的体外透皮吸收有较好的促进作用，其作用与2％月桂氮[艹卓]酮相似。     

不同浓度的月桂氮酮对双氯芬酸钠凝胶剂透皮吸收的影响

目的　通过动物离体透皮吸收试验 ,选择双氯芬酸钠凝胶剂中最佳浓度的月桂氮 艹卓 酮 (氮酮 ,Azone)作为渗透促进剂。方法　采用改良的Franz扩散装置 ,以离体鼠皮为屏障、生理盐水为接受介质 ,研究了不同浓度的月桂氮 艹卓 酮 (0 %、1%、2 %、3%、5 %Azone)对双氯芬酸钠凝胶剂透皮吸收的影响。结果　双氯芬酸钠凝胶剂 12h累积透皮释药百分率依次为 38.4 2 %、6 2 .35 %、72 .80 %、32 .10 %、5 5 .36 %。结论　Azone促进双氯芬酸钠凝胶剂透皮释药的最大浓度为 2 % ,筛选出 2 %月桂氮 艹卓 酮作为促进剂 ,制备了具有良好经皮吸收性能的双氯芬酸钠凝胶剂。     

水溶性月桂氮(艹/卓)酮对达克罗宁粘膜促渗作用的药效学研究

目的 :考察月桂氮艹卓 酮的粘膜促渗作用。方法 :以达克罗宁为模型药 ,用青蛙和蚯蚓试验法分别研究了月桂氮艹卓 酮对达克罗宁麻醉效果的影响。结果 :与不含月桂氮艹卓 酮的样品比较 ,体积分数为 1 %的月桂氮艹卓 酮能显著促进达克罗宁的粘膜渗透作用 (P <0 .0 1 ) ,短麻缩醉的潜伏期 ;用 0 .5%的月桂氮艹卓 酮作促渗剂 ,可使达克罗宁的麻醉作用效价强度提高 3倍。结论 :考察了月桂氮 艹卓 酮对达克罗宁粘膜促渗作用的影响 ,其结果为进一步研究月桂氮艹卓 酮在透皮给药系统方面的应用提供了有益的参考     

月桂氮zhuo酮对青藤碱凝胶剂的透皮吸收作用

目的：考察不同浓度月桂氮Zhuo酮（azone)对青藤碱凝胶透皮作用的影响，为青藤碱凝胶剂的处方筛选提供依据。方法：采用改良Franz扩散池，以离体大白鼠皮肤为透皮屏障，配制含不同浓度月桂氮Zhuo酮的青藤碱凝胶，用HPLC法测定青藤碱的透皮吸收量。结果：青藤碱凝胶含2%azone时透皮吸收最好。其体外累积渗透量及促透速率最大。青藤碱凝胶剂的体外渗透药动学符合Higuchi方程。结论：选择2%azone作为青藤碱凝胶剂的促透剂。     

月桂氮(艹卓)酮对13种中药的促进透皮吸收作用

目的:讨论月桂氮(艹卓)酮对13种中药的促透皮吸收作用.方法:采用仪器法测定药物在实验模型中的透皮吸收情况及其影响因素.结果:月桂氮(艹卓)酮对13种中药均有显著的促透皮吸收作用.结论:提示月桂氮(艹卓)酮对中药的促透皮吸收作用对中药经皮吸收制剂的开发研究具有重要意义.     

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.