Mesalazine in treating diverticular disease of the colon

Evaluation of: Kruis W, Meier E, Schumacher M, Mickisch O, Greinwald R, Mueller R; German SAG-20 Study Group. Randomised clinical trial: mesalazine (Salofalk granules) for uncomplicated diverticular disease of the colon – a placebo-controlled study. Aliment. Pharmacol. Ther. 37(7), 680–690 (2013).

Although diverticular disease (DD) is one of the commonest diseases in the western world, robust evidences about its treatment are lack so far. A recent, placebo-controlled study found mesalazine effective in obtaining pain relief in patients suffering from DD. A brief comment is provided herein in order to assess the rationale of this drug in treating DD.     

Long-term treatment with mesalazine and rifaximin versus rifaximin alone for patients with recurrent attacks of acute diverticulitis of colon

BACKGROUND/AIMS: To compare efficacy of combined therapy with rifaximin and mesalazine versus rifaximin alone in treatment of patients with recurrent diverticulitis in order to evaluate: 1) rapidity in improvement of symptoms, 2) regulation of bowel attacks, 3) prevention of recurrence of diverticulitis. METHODS: A total of 218 consecutive eligible patients (131 males, 87 females age 64.3 years, range 51-79), affected by diverticulitis were monitored. Of these, 109 patients were treated with rifaximin 400 mg bid plus mesalazine 800 mg tid for 7 days, followed by rifaximin 400 mg bid plus mesalazine 800 mg bid for 7 days/month (group A); 109 patients were treated with rifaximin 400 mg bid for 7 days, followed by rifaximin 400 mg bid for 7 days/month (group B). Colonoscopy was performed after 3, 6 and 12 months of therapy. RESULTS: At end of follow-up, 193 patients were fully compliant to therapy Two patients died during study (1 in group A, 1 in group B), while four patients were lost to follow-up [1 in group A (0.91%) and 3 in group B (2.75%)]. The only side-effects recorded were transient urticaria (1 in group B, 0.91%) and epigastric pain (9 in group A, 8.25%). Severity of symptoms improved significantly in group A vs group B within 3 months (p < 0.005, p < 0.001 and p < 0.0001 and p < 0.0005 at 3, 6, 9 and 12 months, respectively). Bowel habits inproved significantly in group A vs group B within 3 months (p < 0.005, p < 0.0005, p < 0.001 and p < 0.0001 at 3,6,9 and 12 months respectively). Symptomatic recurrence of diverticulitis occurred in 3 patients in group A, while 13 patients showed recurrence of diverticulitis in group B (p < 0.005) during follow-up. CONCLUSIONS: This study clearly shows that rifaximin plus mesalazine are more effective than rifaximin alone in resolution of symptoms and prevention of recurrence of diverticulitis.     

双歧杆菌三联活菌胶囊联合美沙拉嗪栓剂治疗UC的临床观察

目的：探讨双歧杆菌三联活菌胶囊联合美沙拉嗪栓剂治疗溃疡性结肠炎（UC）的临床疗效及安全性。方法将收治的60例UC患者按随机数字表分为观察组和对照组,每组30例。2组均予美沙拉嗪栓剂治疗,1 g/次,2次/d,塞肛,在此基础上,观察组加用双歧杆菌三联活菌胶囊,0.42g/次,3次/d,饭后半小时温水服用。2组疗程均为4周。观察治疗前后的临床疗效、改良Mayo评分及不良反应发生率,进行对比分析。结果观察组的总有效率为93.33%,与对照组比较,差异有统计学意义（P＜0.05）。2组治疗后的改良Mayo评分分别为（1.19±1.72）分、（3.21±1.36）分,组间比较,观察组的改善优于对照组（P＜0.05）,而2组不良反应发生率分别为6.67%。13.33%,组间比较无统计学意义。结论培菲康联合美沙拉嗪栓剂治疗溃疡性结肠炎疗效显著。     

抗结肠炎药美沙拉嗪的合成及结构鉴定

报告了抗溃疡性结肠炎药美沙拉嗪的合成工艺及结构鉴定。工艺过程包括重氮化反应、重氮耦合反应和还原反应 ,总收率 6 0 % ,产品含量≥ 99.0 %。通过元素分析、紫外吸收光谱、红外吸收光谱、1 H-核磁共振谱、1 3 C-核磁共振谱和质谱确证了结构     

Maternal use of 5-aminosalicylates in early pregnancy and congenital malformation risk in the offspring

Abstract

Objective. Most previous studies have failed to demonstrate any effect of maternal use of 5-aminosalicylates (5-ASA) on malformation risk, but the number of infants studied have, in most cases, been low. The objective of the study was to get data from a large study with prospectively ascertained exposure information. Material and methods. The study was based on data in the Swedish Medical Birth Register (1996–2011) where identification of maternal drug use is made from midwife interviews in early pregnancy. The presence of congenital malformations was ascertained from three national registers. Adjusted odds ratios were calculated by the Mantel-Haenszel methodology. Results. Among 1,552,109 women, 3651 with 3721 infants had reported the use of 5-ASAs in early pregnancy. The risk of a major malformation was increased (1.37, 95% confidence interval = 1.17–1.62) and still more for a cardiovascular defect (1.74, 1.37–2.22). This effect seemed to be influenced by concomitant use of systemic glucocorticosteroids or immunosuppressants but some confounding by indication may also exist. There was no marked difference between the four 5-ASA drugs studied. Conclusions. Infants born of women who use 5-ASA drugs in early pregnancy have an increased risk of a congenital malformation, notably a cardiovascular defect. This could be a drug effect or an effect of an active inflammatory bowel disease.     

美沙拉嗪结肠靶向微丸的制备和体外评价

目的以结肠溶型丙烯酸树脂为包衣材料制备美沙拉嗪pH控制型结肠靶向微丸,评价其体外释药特性。方法挤出滚圆法制备美沙拉嗪微丸,采用L934正交设计实验优化工艺条件,流化床包衣机包衣,采用U884均匀设计试验优化工艺参数,考察了微丸圆整度、收率及体外释药特性。结果优化条件所得的微丸外观圆整,粒径分布均匀,收率高,在人工胃液中2h、人工小肠液中4h累计释放率<5%,人工结肠液1h累计释放率>95%,具有明显的结肠靶向释药特性。结论美沙拉嗪结肠靶向微丸具有良好的体外结肠靶向释药特性,可进一步进行体内释药行为考察。     

时间控制型结肠定位释药片体外释放的影响因素

以美沙拉嗪为模型药物，制备含不同有机酸的片芯，依次包内隔离层（HPMC）、胃溶衣层（丙烯酸树脂Ⅳ）、外隔离层（HPMC）和肠溶衣层（HPMCP），制得时间依赖型结肠定位释药片。考察了有机酸种类、用量及内隔离层和胃溶衣层增重对片剂释放时滞的影响。结果表明，片芯含琥珀酸50mg、内隔离层和胃溶衣层增重分别为1．2％和12％的片剂，在模拟胃肠液中的时滞约5h,6h累积释放达85％以上。     

Dose loading with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters

AIMS: Tissue concentrations of 5-aminosalicylic acid (5ASA) and its metabolites may influence the clinical course of inflammatory bowel disease. Since the factors that determine tissue drug concentrations are unknown we have studied the relationships between the oral dose of delayed-release mesalazine, rectal tissue drug concentrations and standard pharmacokinetic parameters. METHODS: Twelve healthy volunteers were studied following 7 days treatment with 1.2, 2.4 and 4.8 g of delayed-release mesalazine daily. 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid concentrations were measured in serum, urine, stool and rectal tissue biopsies. RESULTS: Serum concentrations and 24 h urinary excretion of 5ASA and N-acetyl 5ASA increased as the oral dose of mesalazine was increased from 1.2 g through 2.4 g to 4.8 g daily (serum area under curve (AUC):5ASA = 3. 9, 15.4 and 46.8 microg ml-1 h, P < 0.0001; N-acetyl 5ASA = 17.2, 30. 9 and 57.8 microg ml-1 h, P < 0.0001: urinary excretion: 5ASA = 1.8, 85.5 and 445 mg, P < 0.0001; N-acetyl 5ASA = 250, 524 and 1468 mg, P < 0.0001, respectively). Faecal 5ASA excretion increased as the oral dose increased from 1.2 g to 2.4 g but did not increase further with 4.8 g daily dosing whereas faecal N-acetyl 5ASA excretion was similar at all three doses. Rectal tissue concentrations of 5ASA increased markedly, and N-acetyl 5ASA increased modestly, as the dose of oral mesalazine increased from 1.2 g to 2.4 g daily but neither increased further with 4.8 g daily dosing. CONCLUSIONS: The relationship between the ingested dose of delayed-release mesalazine and rectal tissue drug concentrations is complex. Factors other than dose are likely to be important determinants of rectal tissue drug concentrations.