pH对氢溴酸西酞普兰溶液化学稳定性及油水分配系数的影响

摘 要 目的：研究pH对氢溴酸西肽普兰（CTH）溶液化学稳定性以及油水分配系数（P）的影响。 方法: 采用HPLC UV法测定CTH的浓度;分别测定在不同pH下,药物的降解速率以及在正辛醇 水/缓冲液系统中的P值。 结果: 在介质pH≤8.0时, CTH的降解速率很小;当pH＞8.0 时,随着pH的增大,CTH的降解速率显著增加;CTH在正辛醇 水系统中的P值为4.51。在正辛醇 缓冲液系统中,当pH≤5.0 时,CTH的P值远＜1;当 pH＞5.0时,随着pH增加,药物的P值逐渐增大。结论: 介质pH对CTH溶液的化学稳定性以及P值均有明显影响。     

盐酸奈必洛尔平衡溶解度及表观油水分配系数的测定

摘 要 目的：测定盐酸奈必洛尔的平衡溶解度和表观油水分配系数,为药物新剂型的研究与开发提供试验基础。方法: 采用高效液相色谱法测定盐酸奈必洛尔溶液的含量,运用饱和溶液法测定盐酸奈必洛尔在纯水、0.1 mol·L^-1 盐酸溶液及不同pH磷酸盐缓冲液（pH2.0,pH6.8,pH7.4,pH8.0）中的平衡溶解度;通过摇瓶法测定其在正辛醇 水/缓冲液体系中的表观油水分配系数。结果: （37±0.5）℃下,盐酸奈必洛尔在纯水和0.1 mol·L^-1 盐酸的平衡溶解度分别为722.53 μg·mL^-1和56.07 μg﹒mL^-1,在正辛醇 水/盐酸体系中表观油水分配系数(Log P)分别为1.17和1.32。在pH2.0～7.4的磷酸盐缓冲液中,盐酸奈必洛尔的平衡溶解度和表观油水分配系数随pH升高,分别呈现出降低和增加的趋势;而当pH从7.4增加至8.0时,平衡溶解度增加,表观油水分配系数降低。结论:本文建立的含量测定方法简单可靠,盐酸奈必洛尔水溶性差,其平衡溶解度和表观油水分配系数呈现出pH依赖性。     

双烟酸姜黄素酯平衡溶解度及表观油水分配系数的测定

摘 要 目的：测定双烟酸姜黄素酯平衡溶解度和油水分配系数,为研究新剂型提供基础。方法: 将双烟酸姜黄素酯分别溶解于pH 1.2~7.8 的缓冲溶液介质中,利用HPLC法定量分析,以饱和法测定双烟酸姜黄素酯的平衡溶解度,以摇瓶法测定正辛醇 水及缓冲盐溶液中双烟酸姜黄素酯的表观油水分配系数。结果:双烟酸姜黄素酯在pH 6.8时的溶解度最大,双烟酸姜黄素酯的油水分配系数在pH 1.2,pH 5.8,pH 6.5,pH 7.8中lgPap值落在有利于体内药物的吸收范围（lgPap值为1.69~1.98）。但在其pH 2.0,5.0,6.8时lgPap值大于2,亲脂性较强。结论:双烟酸姜黄素酯的平衡溶解度和表观油水分配系数与缓冲溶液介质的pH有关。在溶解度相对较大的pH下脂溶性较强,难以被人体吸收,需要进一步做剂型研究。     

肉桂酸与桂皮醛的平衡溶解度及表观油水分配系数的测定

摘 要 目的：测定肉桂酸与桂皮醛的平衡溶解度及表观油水分配系数(Papp)。方法: 采用HPLC法测定肉桂酸与桂皮醛在不同pH的缓冲溶液中的平衡溶解度;结合摇瓶法测定其在不同pH缓冲盐溶液及正辛醇 水溶液中的表观油水分配系数。结果:在pH 7.8的缓冲溶液中肉桂酸的平衡溶解度最大,pH 6.8的缓冲溶液中桂皮醛的平衡溶解度最大;肉桂酸与桂皮醛在正辛醇饱和的水溶液中lgPapp值分别为0.85与1.26, 在不同磷酸盐缓冲液中（pH 1.2～7.8）的lgPapp范围分别在-1.04～2.27,0.29～1.67之间。结论:此法简便、准确、快捷,可预测化学成分在体内的吸收;在胃肠道环境中,桂皮醛的吸收较好,肉桂酸在胃中的吸收较差,在肠道中吸收较好。     

黄蜀葵花总黄酮中金丝桃苷的平衡溶解度和表观油水分配系数测定

摘 要 目的：测定黄蜀葵花总黄酮中金丝桃苷的平衡溶解度和表观油水分配系数。方法: 采用HPLC法测定金丝桃苷在水、不同有机溶剂和不同pH缓冲液中的平衡溶解度,用摇瓶法测定金丝桃苷在正辛醇 水/缓冲液中的表观油水分配系数。结果: 37℃下金丝桃苷在水中的平衡溶解度为231.58 mg·L^-1,表观油水分配系数为0.907（logPapp=-0.04）;常用有机溶剂甲醇对金丝桃苷的溶解性较好,为6 579.21 mg·L^-1;在不同pH缓冲溶液中,溶解度随着pH的升高逐渐升高,油水分配系数随着pH的升高逐渐降低。结论:金丝桃苷的水溶性差,pH对其溶解度和表观油水分配系数均有较大影响。     

阿齐沙坦油水分配系数的测定

目的 测定阿齐沙坦的油水分配系数。方法 配制不同pH值的磷酸盐缓冲液,以正辛醇-磷酸盐缓冲液作为分散系统,摇瓶法作为测定方法,照紫外-可见分光光度法（《中国药典》2010年版附录ⅣA）进行测定。通过阿齐沙坦分配平衡后在油相（正辛醇）和水相的浓度比,计算油水分配系数。结果 在正辛醇-磷酸盐缓冲液体系中,pH＝3.0时阿齐沙坦的油水分配系数为3.78,pH＝7.0时阿齐沙坦的油水分配系数为?0.30。结论 应用摇瓶-紫外分光光度法,能够准确测定阿齐沙坦的油水分配系数,并由此推测其体内过程。     

氢溴酸沃替西汀油水分配系数研究及其片剂的一致性评价

目的 测定氢溴酸沃替西汀油水分配系数并对其片剂进行一致性评价。方法 模拟体内环境配制不同pH的缓冲液(或水溶液),以正辛醇-缓冲液(或水溶液)为分散系统,摇瓶法作为测定方法,采用高效液相色谱法进行测定。通过氢溴酸沃替西汀分配平衡后在油相(正辛醇)和水相的浓度比,计算氢溴酸沃替西汀的油水分配系数,并对比测定氢溴酸沃替西汀片剂(自制片、原研片)中氢溴酸沃替西汀的油水分配系数。结果 在正辛醇-缓冲液(或水溶液)体系中,pH=1.0时氢溴酸沃替西汀的油水分配系数为2.20;pH=4.5时为2.18;pH=6.8时为0.823;在水中时为0.657。结论 采用摇瓶-高效液相色谱法能够准确测定氢溴酸沃替西汀的油水分配系数,为预测体内吸收过程提供依据。并且氢溴酸沃替西汀自制片和原研片中氢溴酸沃替西汀油水分配系数结果一致。     

草乌甲素胶丸的体外溶出度考察

摘 要 目的： 建立草乌甲素胶丸的溶出度测定方法。方法: 采用小杯法,以pH1.2的人工胃液（含0.25%十二烷基硫酸钠溶液）、pH4.0醋酸盐缓冲液（含0.5%十二烷基硫酸钠溶液）、pH6.8磷酸盐缓冲液（含0.5%十二烷基硫酸钠溶液）及水（含0.25%十二烷基硫酸钠溶液）为溶出介质,转速50 r·min^-1,取样时间30 min测定溶出度,采用高效液相色谱法测定草乌甲素的溶出量,绘制溶出曲线。结果: 草乌甲素胶丸批内批间的溶出度结果差异较小,15 min 后样品的释放百分率趋于平稳。草乌甲素的检测浓度在2~20μg·ml^-1(r=0.999 2)范围内呈良好的线性关系,在4不同溶出介质中的回收率均在99%以上。结论: 该方法简便、准确, 重复性好, 可用于该胶丸的溶出度测定。     

HPLC法测定安乃近注射液中苯甲醇的含量

摘 要 目的：建立高效液相色谱法测定安乃近注射液中苯甲醇的含量。方法: 采用Xtimate C18（250 mm×4.6 mm,5 μm）柱,流动相为磷酸盐缓冲液（取磷酸二氢钠6.0 g,加水1 000 ml,加三乙胺1 ml,用氢氧化钠溶液调pH至7.0） 甲醇（75∶〖KG-*2〗25）,流速为1.0 ml·min^-1,检测波长为254 nm,柱温：30℃,进样量：5 μl。结果:苯甲醇检测线性范围为76.88～269.08 μg·ml^-1（r=0.998 5）,平均回收率为98.77%（RSD=0.77%,n=9）。结论:该方法准确、重复性好,可用于安乃近注射液中苯甲醇含量的测定。     

双氯芬酸钠平衡溶解度和表观油水分配系数的研究

目的 测定双氯芬酸钠平衡溶解度及表观油水分配系数,为药物评价、新剂型设计与开发提供试验依据。方法 采用反相高效液相色谱法（RP-HPLC）测定双氯芬酸钠在不同介质中的平衡溶解度,使用Diamonsil C₁₈（150 mm×4.6 mm,5 μm）色谱柱,甲醇-水-磷酸（80∶19∶1）为流动相,体积流量为0.8 mL/min,检测波长为276 nm,柱温为32 ℃;采用摇瓶法测定双氯芬酸钠在正辛醇-水/缓冲液体系中的表观油水分配系数。结果 32 ℃时,双氯芬酸钠在蒸馏水和生理盐水中的平衡溶解度分别为18.2、5.52 mg/mL;在肉豆蔻酸异丙酯（IPM）、油酸乙酯中的平衡溶解度分别为0.637、1.97 mg/mL;在正辛醇/水体系中的表观油水分配系数为1.41（lgP＝0.15）;在pH 5.0～7.4缓冲液中,其平衡溶解度随pH值升高而增大,表观油水分配系数随pH值升高而降低;结论 pH对双氯芬酸钠的平衡溶解度和表观油水分配系数有较大影响。     

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.     

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.