维甲酸自乳化制剂的处方筛选初步研究

目的:筛选维甲酸自乳化制剂最佳处方条件。方法:以维甲酸在不同种类及比例的油相、表面活性剂中的溶解度为指标,通过溶解度试验及三相图绘制,筛选维甲酸自乳化制剂的最佳处方。结果:维甲酸的自乳化制剂最佳处方为维甲酸/肉豆蔻酸异丙脂/吐温-85/异丙醇(0·01∶0·938∶0·402∶0·15,g∶g∶g∶mL)。结论:按照上述比例配制的维甲酸自乳化制剂符合相关要求。     

高效液相色谱法同时检测人血清中全反式及13—顺式维甲酸浓度

目的 :建立高效液相色谱方法同时检测人血清中全反式及 13 -顺式维甲酸浓度。方法 :色谱柱 :μBondapakC18(3 9mm× 30 0mm) ,流动相 :甲醇 -醋酸铵缓冲液 (85∶15 ) ,流速 :0 8mL·min-1,紫外检测波长 :340nm ,柱温 :2 2℃ ,血清样品经乙醚 2次提取 ,按内标法定量 ,内标物选用对二甲氨基苯甲醛。结果 :全反式及 13-顺式维甲酸的线性范围分别在 0 8～ 112 0 μg·L-1和 0 82～ 1312 μg·L-1,最低检测浓度均为 0 6μg·L-1。全反式维甲酸测定的平均回收率为 98 86 %～ 10 5 2 % ,日内、日间精密度RSD为 0 84%～ 5 5 % ,13-顺式维甲酸测定的平均回收率为 10 1 6 %～ 10 1 8% ,日内、日间精密度RSD为 1 4%～ 5 7%。结论 :本方法灵敏、准确 ,样品处理简便易行 ,适用于全反式维甲酸的临床药动学研究     

人血浆中全反式维甲酸、13-顺式维甲酸和9-顺式维甲酸浓度的监测

目的建立高效液相色谱法同时测定人血浆中全反式维甲酸、13-顺式维甲酸和9-顺式维甲酸浓度。方法色谱柱为KromasilC18柱(4.6mm×250mm,5μm);柱温为室温。流动相A:甲醇;流动相B:0.01mol/L醋酸钠缓冲液(pH=5.7),梯度洗脱,流速1ml/min;检测波长340nm。结果全反式维甲酸、13-顺式维甲酸和9-顺式维甲酸血药浓度在1～200ng/ml范围内,浓度与峰面积比有良好的线性关系,最低检测浓度为0.5ng/ml。全反式维甲酸方法回收率为97.22%～108.80%,日内RSD≤8.24%,日间RSD≤11.34%;13-顺式维甲酸方法回收率为98.62%～104.80%,日内RSD≤8.02%,日间RSD≤11.70%;9-顺式维甲酸方法回收率为97.74%～102.24%,日内RSD≤7.72%,日间RSD≤9.17%。结论本方法简单、快速、灵敏、重现性好,适用于全反式维甲酸、13-顺式维甲酸和9-顺式维甲酸临床血药浓度监测及人体药代动力学研究。     

维甲酸脂质体的制备及评价

目的:制备维甲酸脂质体并对其包封率、粒径、药物含量等进行考察。方法:采用逆向蒸发法制备维甲酸脂质体;高效液相色谱法测定药物含量和包封率;激光散射法和透射电镜测定和观察脂质体粒径和形态。结果:磷脂和胆固醇总的质量浓度在40～50mg·mL~(-1),磷脂与胆固醇的质量比在3:1～4:1时,得到包封率超过90%的维甲酸脂质体;粒径700～800nm,多分散系数(PI)＜0．3,电镜下观察为大单层脂质体。结论:维甲酸脂质体包封率较高,粒径大小均匀,含量符合要求。     

维甲酸羟丙-β-环糊精包合物制备条件的优化及包合过程热力学参数的测定

目的为提高维甲酸的光稳定性、热稳定性及水溶性等而对其进行羟丙 β 环糊精包合物包合条件的研究。方法在单因素考察的基础上 ,采用多因素交叉正交实验对维甲酸的包合条件进行筛选 ,测定包合过程的热力学参数。结果包合的最优条件为 :辅料与药物的投料比 (5∶1 )、包合温度(3 5℃ )、包合时间 (2 4h)、溶剂 (水 )、研磨时间 (1 5min)、离子强度 (无影响 )以及搅拌程度 (低速 )。包合过程的热力学参数为ΔH0 =41 5 8kJ·mol-1,ΔS0 =1 3 8 87J·K-1。结论包合率按包合物中维甲酸的含量与投料的比值计算 ,达到 3 7 5 4% ,优于国内外报道 ,热力学参数数据基本合理。     

染料木素对维甲酸模型大鼠骨密度和微量元素的影响

目的　观察染料木素对维甲酸模型大鼠骨密度和微量元素的影响。方法　维甲酸 70 mg·kg- 1灌胃两周(正常对照组给予等量生理盐水 )后 ,各组大鼠给药如下 :正常对照组和模型组 ig等容量生理盐水 ;骨疏康组以5 .0 g· kg- 1 的骨疏康灌胃 ,染料木素大、中、小剂量组分别以 1 8.0 ,9.0和 4.5 mg· kg- 1 灌胃给药。并分别于0 ,1 ,2 ,4,8,1 2周从各组取 8只大鼠 ,测量大鼠体质量 ,股骨、胫骨长度和质量 ,测定股骨、胫骨和腰椎骨密度和胫骨中微量元素含量。结果　 1染料木素可增加维甲酸模型大鼠的体质量 ,并明显增加维甲酸大鼠的左股骨、左胫骨质量和长度 ( P <0 .0 5或 P <0 .0 1 ) ;2增强维甲酸模型大鼠的骨密度 ( P <0 .0 5或 P <0 .0 1 ) ;3可明显升高维甲酸模型大鼠微量元素含量 ( P<0 .0 5或 P <0 .0 1 )。结论　染料木素可使维甲酸模型大鼠的骨密度显著增加 ,并使骨质微量元素明显增加 ,对治疗骨质疏松症有很好的疗效     

维甲酸固体脂质纳米粒中主药的含量及包封率测定

目的:建立测定维甲酸固体脂质纳米粒(atRA-SLNs)中主药含量及包封率的方法。方法:采用高效液相色谱法测定atRA-SLNs中主药含量,并采用超速离心法分离该制剂中的游离药物,测定其包封率。结果:维甲酸进样量的线性范围为0·016~0·128μg(r=0·9999,n=7);平均回收率为99·36%(RSD=0·37%);3批样品的包封率均大于96·0%。结论:该方法准确可靠、快速简单,可用于该制剂的含量及包封率测定。     

维甲酸洗脱支架的制备与体外释放度研究

［摘要 ］目的探讨维甲酸洗脱支架的制备方法,考察其体外释放度。方法配制溶质浓度分别为10和7 mg &#8226;mL 1的维甲酸层涂层液和聚合物层涂层液,采用气体雾化喷涂法制备维甲酸洗脱支架,在37 ℃、20%甲醇溶液中进行体外释放实验,通过改变维甲酸层中药物百分比以及聚合物层厚度调节维甲酸洗脱支架释放度。结果喷涂溶质中维甲酸含量为30%的涂层液1 mL,或先喷涂50%维甲酸1 mL后,再喷涂聚合物层涂层液0.5 mL,这两种方法制备得到的维甲酸洗脱支架在可以持续释放约1个月。结论两种方法制备得到的维甲酸洗脱支架在体外具有良好的药物控释行为和机械性能,可以满足动物实验要求。     

全反式维甲酸诱导人急性早幼粒白血病HL-60细胞分化的机制

目的研究全反式维甲酸诱导人急性早幼粒白血病HL-60细胞分化机制。方法用流式细胞仪分析维甲酸对HL-60细胞周期变化的影响，用自制的含9 984个已知基因和EST的高密度基因芯片检测HL-60细胞在维甲酸诱导作用下不同时期的基因表达变化。结果HL-60细胞在1 μmol·L^-1维甲酸持续作用2,4和6 d时,流式细胞仪结果显示48%～73%细胞阻断在G0/G1期;基因表达谱分析发现,黏附分子、组织重建蛋白、转运蛋白、核蛋白体蛋白和涉及氧化酶激活途径的基因表达明显升高。结论基因表达谱的研究结果表明,维甲酸作用HL-60细胞与氧化酶激活途径及组织重建蛋白的表达相关联,并揭示了一些已知和未知功能的基因在HL-60细胞分化与细胞凋亡过程中的作用。     

异维甲酸治疗3种皮肤病的回顾性分析

目的:探讨异维甲酸治疗3种皮肤病的临床疗效。方法:689入选病例口服异维甲酸,1个月为1疗程,观察1～3个月。结果:异维甲酸对痤疮、酒渣鼻、角化异常性遗传性皮病都有满意疗效,总有效率为74.36%～80.40%。结论:异维甲酸应用于门诊皮肤科对多种皮肤病见效快、疗效高,不失为一种方便、安全、前景看好的药物。     

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.