氯沙坦钾氢氯噻嗪片体外药物释放关键影响因素的研究

目的 研究影响氯沙坦钾氢氯噻嗪片体外药物释放的关键因素。方法 以pH值3.5缓冲液为溶出介质,采用桨法+沉降篮(转速50 r·min^–1)测定体外溶出量。HPLC色谱柱为Kromasil 100-10 C₈,流动相为0.01 mol·L^–1磷酸二氢钾溶液(pH值2.5)-乙腈(2∶3),检测波长230 nm,进样量20 μL,流速为2.3 mL·min^–1。结果 研究发现,证实自研片和原研片在该介质中释放差异的主要原因系包衣粉中着色剂不同。进一步研究发现,喹啉黄铝色淀本身的形态和性质在酸介质中有延缓药物释放的作用,此外包衣粉中的水溶性聚合物羟丙纤维素与pH值3.5缓冲液的相互作用也是延缓药物释放的重要因素。结论 速释薄膜包衣粉中着色剂和水溶性聚合物实际上对药物的体外释放有直接的影响。     

Effects of the DASH diet and losartan on serum urate among adults with hypertension: Results of a randomized trial

Serum urate is a risk factor for hypertension and gout. The DASH diet and losartan independently lower blood pressure (BP); however, their effects on serum urate are understudied. We performed a post-hoc analysis of the DASH-losartan trial, which randomized participants with hypertension in parallel fashion to the DASH diet or a standard American diet (control) and in crossover fashion to 4-week losartan or placebo. Serum urate was measured at baseline and after each 4-week period. Diets were designed to maintain weight constant. We examined the effects of DASH (vs control) and/or losartan (vs placebo) on serum urate, overall and among those with baseline serum urate ≥6 mg/dL, using generalized estimating equations. Of 55 participants (mean age 52 years, 58% women, 64% Black), mean (±SD) baseline ambulatory SBP/DBP was 146±12/91±9 and mean (±SD) serum urate was 5.2±1.2 mg/dL. The DASH diet did not significantly reduce urate levels overall (mean difference −0.05 mg/dL; 95%CI: −0.39, 0.28), but did decrease levels among participants with baseline hyperuricemia (−0.33 mg/dL; 95%CI: −0.87, 0.21; P-interaction=0.007 across hyperuricemia groups). Losartan significantly decreased serum urate (−0.23 mg/dL; 95%CI: −0.40, −0.05) with greater effects on serum urate among adults <60 years old versus adults ≥60 years old (−0.33 mg/dL vs 0.16 mg/dL, P interaction = 0.003). In summary, the DASH diet significantly decreased serum urate among participants with higher urate at baseline, while losartan significantly reduced serum urate, especially among younger adults. Future research should examine the effects of these interventions in patients with hyperuricemia or gout.