莫达芬尼酸及莫达芬尼砜的核磁共振波谱研究

目的：对莫达芬尼酸和莫达芬尼砜进行核磁共振波谱(NMR)研究。方法：采用1D—NMR(^1H、^13C-NMR、DEPT)和2D-NMR(^1H-^1HCOSY、HMQC、HMBC)等现代核磁技术检测莫达芬尼酸和莫达尼酸的结构。结果：归属了莫达芬尼酸和莫达芬尼砜的H、C谱线。结论：首次报道了莫达芬尼酸和莫达芬尼砜的碳谱数据。     

环氧树脂/聚醚砜/纳米氧化铝复合材料的力学性能及介电性能

以甲基纳迪克酸酐（MNA）为固化剂,制备了环氧树脂/聚醚砜/纳米氧化铝三元复合材料,并对其力学性能、介电性能以及热稳定性能进行了研究,同时探讨了其性能增强机理。结果表明：当聚醚砜（PES）和纳米氧化铝（nano-Al₂O₃）的质量分数分别为15%和3%时,环氧树脂/15PES/3Al₂O₃复合材料的冲击强度、拉伸强度和弯曲强度分别达到45.7 kJ/m²、87 MPa和180 MPa,与纯环氧树脂相比,均有大幅度的提高。在测试频率为100 Hz时,复合材料的介电常数和介电损耗分别为7.7和0.013 5,介电性能较纯环氧树脂也有一定提高。此外,热分解温度比纯环氧树脂的提高了73℃,热稳定性得到提高。     

双-三氯甲基砜对雄大鼠抗生育作用及其可逆性的研究

用略加改进的MB 50程序,进一步对双 三氯甲基砜(BTS)进行药效鉴定。结果表明,BTS10mg·kg^-1po,每周6次连服8周或30mg·kg^-1连服4周,可使SD雄鼠丧失生育力,附睾尾部精子密度,特别是精子活率,与对照比较下降非常显著(P<0.001)。给药鼠的体重、性行为、血睾酮水平以及主要内脏组织学观察均与对照无明显差异。30mg·kg^-1用药4周大鼠即不育,继续用药4周动物保持不育状态,停药4周生育力开始恢复,第6周后生育力全部恢复至正常水平。结果提示BTS有雄性抗生育作用。     

Binding of Sulfinpyrazone and its Metabolites in Human Serum and in Solutions of Human Serum Albumin

Abstract: The binding of sulfinpyrazone, its sulfone metabolite and its sulfide metabolite to serum protein was studied by equilibrium dialysis. At 20 μg/ml 99.1% of the parent compound was bound in serum, whereas 99.8% of the sulfide and 98.3% of the sulfone were bound at this concentration. The binding of the three compounds were studied in diluted serum and in solutions of human serum albumin (HSA). There was no evidence of binding to proteins other than albumin. The association constants to primary and secondary binding sites and the number of binding sites were calculated. For the sulfide a lower K₁-value in serum (0.76·10⁶ M^?1) than in the HSA solution (1.8·10⁶ M^?1) indicated the possible presence of a competitively bound substance in serum. In undiluted serum no displacing effect of the sulfide on sulfinpyrazone binding was found when both compounds were present in a concentration of 20 μg/ml, but in a HSA solution a pronounced sulfide induced displacement of the sulfinpyrazone from its primary binding site was shown. Acetylation of HSA depressed the binding of sulfinpyrazone but in undiluted serum there was no other effect on sulfinpyrazone binding by the addition of acetylsalicylic acid than could be explained by the displacing effect of salicylic acid. At concentrations at 20 μg/ml of sulfinpyrazone and above 50 μg/ml of the displacing agent significant displacement was demonstrated with phenylbutazone, tolbutamide and salicylic acid.     

Use of omeprazole sulfone in a single plasma sample as a probe for CYP3A4

Objective The hydroxylation of omeprazole, measured as the ratio of omeprazole/5-hydroxyomeprazole in a plasma sample taken 3 h after an oral dose, is an established method to determine CYP2C19 activity, and the ratio of omeprazole AUC/omeprazole sulfone AUC has been used for assessing CYP3A4 activity. The aim of this study was to determine whether the latter ratio from a single 3-h sample can also be used for CYP3A4 phenotyping.Methods Plasma levels of omeprazole and omeprazole sulfone were analyzed by reversed-phase high-performance liquid chromatography in a blood sample drawn 3 h after intake of a single oral 20-mg dose of omeprazole by 22 healthy subjects and five patients with newly diagnosed epilepsy. The procedure was repeated on the 4th day of 200 mg of ketoconazole intake (10 subjects), after 3 weeks of 150–200 mg twice-daily carbamazepine (five patients), and on the 6th day of 4 mg twice-daily tolterodine (12 subjects). Five subjects also took 100 mg and 50 mg of ketoconazole for 3 days before concomitant intake with omeprazole.Results The mean log10(omeprazole/omeprazole sulfone) ratio was 0.18 3 h after intake of omeprazole alone. After concomitant intake of ketoconazole, the corresponding value was 1.38 (p<0.001); after intake of carbamazepine it was −0.42 (p<0.05); and after tolterodine it was 0.29 (not significant). In the five subjects taking increasing doses of ketoconazole, the ratio was 0.11, 0.79, 1.2, and 1.5 after 0, 50, 100, and 200 mg of ketoconazole, respectively. The correlation between the metabolic ratios from the AUC_(0-6h) and from the single 3-h samples was very good, with a correlation coefficient of 0.92 (p<0.001).Conclusions A single blood sample taken 3 h after intake of 20 mg of omeprazole can be reliably used to phenotype for both CYP2C19 and CYP3A4 activity.Financial support was obtained from the National Network for Drug Development, within the Foundation for Strategic Research, Sweden.