阿托伐他汀自微乳释药系统的制备和评价

目的制备阿托伐他汀自微乳，为自微乳释药系统的处方设计和体内外评价提供参考。方法采用伪三元相图法研究不同乳化剂、助乳化剂和油相形成微乳的能力和区域，绘制不同处方组成的相图，在此基础上制备阿托伐他汀自微乳，比较温度、介质、稀释等因素对自微乳效率的影响，进行自微乳时间、所成微乳的形态、粒径分布、zeta电位、含量和稳定性等体外评价Beagle犬体内药代动力学研究。结果理想的处方经分散后可得到平均粒径在100 nm以下、呈高斯分布的微乳，稳定性好，自微乳效率高，在Beagle犬体内的吸收明显高于市售片剂。结论本文首次研制阿托伐他汀自微乳，稳定性好，在Beagle犬体内的生物利用度高。     

银杏总黄酮自乳化释药系统的制备及其性质研究

摘 要 目的：制备银杏总黄酮自乳化释药系统,并对其体外特性进行评价。方法: 通过溶解度试验、处方配伍和伪三元相图中形成微乳区域面积的大小来确定银杏总黄酮自乳化释药系统的处方组成,并考察了该释药系统经水稀释后形成微乳的外观、形态、粒径分布、Zeta 电位以及体外药物溶出度。结果: 所得银杏总黄酮的自乳化释药系统的处方组成：油酸聚乙二醇甘油酯（油相）、聚山梨酯 80（表面活性剂）、二乙二醇单乙基醚（XCF,助表面活性剂）,最佳配比为10∶6∶4,载药量10.0 mg·g^-1。经水稀释后形成澄清、透明状溶液,透射电镜观察微乳呈大小均一,球状分布,平均粒径为（87.4±26.7）nm,Zeta电位为（13.1±1.5）mV。溶出度结果表明,银杏总黄酮的自乳化释药系统在pH1.2的盐酸溶液中45 min内累积溶出度可达（96.1±4.8）%。结论:自乳化释药系统能够显著提高银杏总黄酮的体外溶出速度,有望成为银叶总黄酮的优良口服制剂。     

葛根素自微乳的制备工艺研究

目的筛选葛根素自微乳的处方。方法通过药物溶解度实验和伪三元相图的绘制,以粒径大小和分布为指标,筛选油相、乳化剂、助乳化剂的处方配比。测定葛根素自微乳释药系统的溶出度。结果确定的葛根素自微乳处方比例为葛根素∶油酸聚乙醇甘油酯(labrafil M 1944CS)∶聚氧乙烯氢化蓖麻油(RH-40)∶聚乙二醇400(PEG 400)=9.1%∶36.4%∶36.4%∶18.1%。结论通过研究确定了最优化的葛根素自微乳处方,微乳粒径分布均匀。     

灯盏花素固体自微乳剂的制备及体外溶出度的评价

目的研制灯盏花素固体自微乳剂(灯盏花素-SSMEDDS),并考察其体外溶出度。方法通过伪三元相图优化处方工艺,研究自微乳化系统中的油相、乳化剂及助乳化剂的组成和用量,筛选灯盏花素固体自微乳剂的最佳处方,并考察其理化性质及体外溶出度。结果灯盏花素固体自微乳剂的处方中,灯盏花素、GTCC、吐温-20、PEG-400、Transcutol-P、甘露醇的质量比为0.75∶0.69∶10.0∶7.02∶16.36∶65.17;乳滴粒径为34.62 nm;溶出度受溶出介质的影响为:人工肠液>水>人工胃液。结论自微乳剂能够改善灯盏花素的难溶性,固体自微乳剂的制备工艺简单,具有良好的应用前景。     

星点设计效应面法优化非洛地平自微乳给药系统

目的 设计非洛地平自微乳给药系统，并进行体外评价。方法 测定非洛地平的溶解度，考察油相与乳化剂的相容性，绘制伪三元相图，初步设计自微乳处方；运用星点设计效应面法优化自微乳处方；评价自乳化性能和体外溶出行为。结果 非洛地平自微乳处方：油相LABRAFIL M 1944CS为4.4 g，乳化剂Cremophor EL35为5.5 g，助乳化剂PEG400为1.1 g，非洛地平1.0 g；自乳化效率高，乳液澄明稳定，平均粒径为30.4 nm，PDI为0.16；水中溶出很快，5 min内平均溶出度>85%，30 min达99%，24 h后乳滴依然稳定。结论 星点设计-效应面法优化的非洛地平自微乳，自乳化性能高，乳液稳定，显著提高非洛地平的体外溶出度。     

磷脂对自微乳口服吸收、淋巴转运和体外特征的影响

目的以黄芩素为模型药物制备自微乳(SMEDDS),考察磷脂作为联合乳化剂对SMEDDS乳化、体外释放、体内胃肠吸收以及淋巴转运的影响。方法本研究以油酸乙酯为油相,吐温-80/磷脂为联合乳化剂,Transcutol HP为助乳化剂,构建黄芩素自微乳(BA-PC-SMEDDS),对乳化效率、粒径、Zeta电位、长期储存稳定性、大鼠体内药代动力学和淋巴转运等特征进行考察,并与处方中不含磷脂的传统自微乳(CBA-SMEDDS)进行比较。结果当磷脂作为联合乳化剂时,自微乳的长期储存稳定性提高,药物析出现象得到抑制。BA-PC-SMEDDS口服吸收后的AUC_0～_t为CBA-SMEDDS的1.37倍,淋巴转运程度从56.2%提高到68.6%。结论综上所述,处方中使用磷脂作为联合乳化剂,有利于改善SMEDDS的稳定性,提高难溶性药物的口服吸收,且对淋巴转运有促进作用。     

绞股蓝总皂苷自微乳化给药系统的制备

目的绞股蓝总皂苷自微乳化给药系统的制备及评价。方法通过溶解度试验、伪三元相图及星点设计-效应面法,以粒径、Zeta电位、自微乳化时间为指标,筛选最佳处方,并对绞股蓝总皂苷自微乳化给药系统体外释药进行测定。结果绞股蓝总皂苷自微乳的最优处方为:吐温-80 52%,甘油30%,油酸乙酯26%;其平均粒径为51.21 nm,Zeta电位为-13.7 m V,乳化时间为31.54 s,在45 min的体外溶出度是原料药的5倍。结论绞股蓝总皂苷自微乳化给药系统制备工艺可行,能显著提高绞股蓝总皂苷的溶出度。     

4-氨基-2-三氟甲基苯基维甲酸酯自微乳胶囊的研制

目的制备4-氨基-2-三氟甲基苯基维甲酸酯固体自乳化制剂,以解决该药水溶性差的问题,提高药物胃中溶出度和口服生物利用度。方法通过伪三元相图法考察不同乳化剂、助乳化剂和油相形成微乳的能力和区域,制备自微乳。然后采用mix-ture design方法进行处方优化,并对其乳化后粒径、制剂综合评分和载药量进行考察。结果制备出的最佳处方(含HS1570%,PEG400 10%,油酸乙酯20%)自乳化后粒径在30 nm左右,体外溶出10 min即可溶出80%以上。结论该处方制备出的ATPR固体自微乳可用于提高其溶出速度。     

重楼总皂苷自微乳化颗粒剂的制备及体外溶出研究

摘 要 目的：制备重楼总皂苷自微乳化释药系统并固化成颗粒剂,考察其体外溶出情况。方法: 考察重楼总皂苷在不同辅料中的溶解度,并通过绘制由不同比例油相、乳化剂和助乳化剂组成的伪三元相图,确定重楼总皂苷自微乳化释药系统的最优处方,并将自微乳化释药系统固化制备成颗粒剂。评价自微乳化释药系统和自微乳化颗粒剂经水稀释后形成微乳的外观、微观形态、粒径分布、Zeta电位。比较重楼总皂苷自微乳化释药系统以及自微乳化颗粒剂的体外溶出情况。结果: 最终确定重楼总皂苷自微乳化释药系统的处方组成为：丙二醇单辛酸酯作为油相,吐温80作为乳化剂,丙二醇作为助乳化剂,最佳配比为7.0∶1.5∶1.5。重楼总皂苷自微乳化释药系统以及自微乳化颗粒剂经水稀释后形成的微乳外观呈微泛蓝光的澄清、透明状液体;平均粒径分别为（58.6±16.4）nm和（68.1±12.1）nm,PdI分别为（0.183±0.04）和（0.209±0.05）,Zeta电位分别为（-20.2±1.9）mV和（-18.9±1.5）mV;透射电镜下显示微乳呈圆整、规则球状分布。重楼总皂苷自微乳化释药系统以及自微乳化颗粒剂在45 min时药物的溶出度均超过85%。结论: 将重楼总皂苷制备成自微乳化颗粒剂可显著提高药物的体外溶出速度,制备工艺简单可行。     

伊曲康唑自乳化液的制备及质量评价

目的:制备伊曲康唑自乳化液并对其进行质量评价。方法:通过溶解度试验,油相与各种乳化剂、助乳化剂的配伍选择筛选自乳化液的处方。考察该乳化液经水稀释后形成微乳的形态、粒径和Zeta电位,并测定载药量。结果:该自乳化液处方为油相维生素E醋酸酯,乳化剂TranscutolP,助乳化剂CremophorRH40,三者比例为3:12:5。微乳在透射电镜下呈球形,分布均匀,粒径为(296.1±90.7)nm,Zeta电位为(—13.2±1.6)mV,载药量为9.88%。结论:所制自乳化液质量稳定可靠。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.