奥沙拉嗪与柳氮磺吡啶治疗溃疡性结肠炎疗效与安全性的系统评价

目的:评价氨基水杨酸制剂奥沙拉嗪与柳氮磺吡啶对比治疗溃疡性结肠炎的有效性和安全性。方法:计算机检索PubMed、Cochrane library、Embase、SCI、CNKI、万方、维普、CBM数据库。按Cochrane系统评价的方法评价所纳入研究资料质量,并进行Meta分析。结果:共纳入12个随机对照试验(RCT),共1294例溃疡性结肠炎患者。Meta分析结果显示,奥沙拉嗪治疗溃疡性结肠炎在总有效率、复发率方面与柳氮磺吡啶比较,差异无统计学意义(P>0.05);在安全性评价方面,11个RCT比较了二者的不良反应,提示二者差异无统计学意义(P>0.05)。结论:奥沙拉嗪在疗效和安全性方面并不优于柳氮磺吡啶。     

An experimental study on ulcerative colitis as a potential target for probiotic therapy by Lactobacillus acidophilus with or without “olsalazine”

Traditional medical treatments for ulcerative colitis (UC) are still compromised by its adverse effects and not potent enough to keep in remission for long-term periods. So, new therapies that are targeted at specific disease mechanisms have the potential to provide more effective and safe treatments for ulcerative colitis. Probiotics is recently introduced as a therapy for ulcerative colitis. In the present study, Lactobacillus acidophilus was selected as a probiotic therapy to investigate its effects in oxazolone-induced colitis model in rats that mimics the picture in human. The rats were grouped (8 rats each) as normal control group (Group I), Group II served as untreated oxazolone-induced colitis, Group III oxazolone-induced colitis treated with probiotic L. acidophilus (1 × 10⁷ colony-forming units (CFU)/mL/day oral for 14 days), Group IV oxazolone-induced colitis treated with olsalazine (60 mg/kg/day oral for 14 days), Group V oxazolone-induced colitis treated with probiotic L. acidophilus and olsalazine in the same doses and duration. Disease activity index (DAI) was recorded, serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and intrleukin-6 (IL-6) was assessed as inflammatory markers and the histopathological picture of the colon of each rat was studied. Disease activity index (DAI) showed significant positive correlation with the elevated serum levels of CRP (r = 0.741, p < 0.05), TNF-α (r = 0.802, p < 0.05) and IL-6 (r = 0.801, p < 0.05). Treatment with either L. acidophilus (group III) or olsalazine (group IV) resulted in significant reduction in serum levels of CRP, TNF-α and IL-6, as well as disease activity index (DAI). Treatment with combination of L. acidophilus and olsalazine (group V) offered more significant reduction in serum levels of CRP, TNF-α, IL-6 and disease activity index (DAI) when compared to either group II (untreated group), group III (treated with L. acidophilus) or group IV (treated with olsalazine). So, it was concluded that L. acidophilus probiotic could be recommended as adjuvant therapy in combination with olsalazine to achieve more effective treatment for ulcerative colitis. For application in human, this needs to be verified in further clinical studies.     

奥沙拉嗪与水杨酸偶氮磺胺吡啶灌肠治疗溃疡性结肠炎的疗效对比观察

目的比较奥沙拉嗪与水杨酸偶氮磺胺吡啶(SASP)用灌肠方法治疗活动期溃疡性结肠炎的疗效和不良反应。方法采用随机双盲双模拟方法观察40例活动期溃疡性结肠炎的疗效和不良反应,疗程为4周。结果治疗4周末奥沙拉嗪组总体疗效显效率为70%,临床症状显效率、体征消失率、内镜完全缓解率和组织学完全缓解率分别为60%,45%,75%及60%;SASP组总体疗效显效率为50%,临床症状显效率、体征消失率、内镜完全缓解率和组织学完全缓解率分别为50%,30%,55%及50%,2组相比有显著性差异(P<0.05)。结论用奥沙拉嗪灌肠方法治疗活动期溃疡性结肠炎有较好的疗效,且主要不良反应腹泻明显减少。     

Relative bioavailability of olsalazine from tablets and capsules: a drug targeted for local effect in the colon

The aim of this investigation was to compare two formulations of the prodrug olsalazine (OLZ) with regard to local bioavailability of 5-aminosalicylic acid (5-ASA) in the colon. Since 5-ASA can not be measured directly in the colon, the bioavailability was evaluated by studying the plasma concentration and cumulative urinary excretion (Ae) of its main metabolite N-acetyl-5-aminosalicylic acid (ac-5-ASA). The absorption of OLZ was also studied. A single dose of 1g OLZ tablets and capsules was given to nine healthy fasting volunteers in two repeated two-period cross-over studies. Blood and urine samples were collected for 72 and 96 h, respectively. AUC, Cmax and Ae data from both studies were combined for statistical analysis. Ninety per cent confidence limits for differences in mean AUC for ac-5-ASA (tablet-capsule) compared to that of capsules were -0.31 per cent and 30.8 per cent. This indicates bioequivalence if a more relaxed criterion than the conventional +/- 20 per cent is applied, which is justified in this situation. The 90 per cent confidence limits for Cmax were -10.5 per cent and 36.9 per cent while for Ae the values were -20.5 per cent and 23.7 per cent. Within and between subject variability estimates for AUC of ac-5-ASA were 24 per cent and 46 per cent, respectively.     

奥沙拉嗪口服联合灌肠治疗溃疡性结肠炎疗效观察

目的观察奥沙拉嗪胶囊口服联合保留灌肠治疗溃疡性结肠炎（UC）的疗效和安全性。方法71例UC患者随机分为A（37例）、B（34例）两组,分别给予奥沙拉嗪和艾迪莎口服联合保留灌肠,给药4周。结果治疗后两组症状均显著改善（P〈0．05）,A组腹痛、腹泻及黏液血便的改善情况虽优于B组,但差异均无统计学意义（P〉0．05）;A组总有效率虽高于B组（95．9％vs91．2％）,但差异无统计学意义（P〉0．05）,但A组显效率显著高于B组（51．4％vs41．2％）（P〈0．05）;无严重不良反应。结论奥沙拉嗪和艾迪莎口服联合保留灌肠均有较好疗效,但奥沙拉嗪又表现出可提高显效率的优势。     

复合乳酸菌在溃疡性结肠炎治疗中的应用价值

为探讨复合乳酸菌在溃疡忭结肠炎（UC）治疗中的应用价值,本研究采用随机对照方法。将30例轻中度活动期UC患者分为两组．各15例,一组予复合乳酸菌胶囊（聚克,联合奥沙拉嗪治疗（A组）．一组誓纯予奥沙拉嗪治疗（B组）。聚克的用法为每次0．66g（2粒）口服,每天3次;奥沙拉嗪的用法为每次1g口眼,每天4次。两组均治疗1周。结果显示,治疗后两组临床症状总积分、疾病活动指数、肠镜指数积分均显著降低,P〈0．05;其中A组降低更明显,P〈0．05。结果表明,复合乳酸菌剂加奥沙拉嗪治疗轻中度活动期UC安全、疗效肯定,优于单用炎沙拉嗪,值得临床推广应用。     

奥沙拉嗪联合美常安治疗溃疡性结肠炎疗效观察

目的观察奥沙拉嗪联合美常安治疗溃疡性结肠炎的临床疗效。方法选择132例轻、中度溃疡性结肠炎患者,随机分为治疗组（72例）和对照组（60例）。对照组口服奥沙拉嗪,每日3次,每次1.0 g;治疗组加服美常安胶囊（枯草杆菌、肠球菌二联活菌肠溶胶囊）,每日3次,每次2粒,12周为一个疗程,治疗结束后复查肠镜评定疗效。结果治疗组显效率52.8%,总有效率90.3%;对照组显效率31.7%,总有效率73.3%,治疗组明显优于对照组,P〈0.05。结论奥沙拉嗪联合美常安治疗溃疡性结肠炎的疗效优于单用奥沙拉嗪。     

双歧杆菌四联活菌片对溃疡性结肠炎患者免疫功能及Fas/FasL表达的影响

目的:探讨溃疡性结肠炎患者应用双歧杆菌四联活菌片联合奥沙拉嗪治疗临床疗效,及对免疫功能和Fas/FasL表达的影响.方法:本组96例溃疡性结肠炎患者随机分为观察组(n=48)和对照组(n=48).对照组口服奥沙拉嗪治疗,观察组在对照组基础上结合双歧杆菌四联活菌片治疗.两组均以2周为1个疗程,连续服用2个疗程评价两组临床疗效,对血清炎症因子、免疫功能、C-反应蛋白及Fas/FasL表达的影响.结果:观察组治疗2个疗程后总有效率明显高于对照组,差异具有统计学意义(P＜0.05);观察组治疗后白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)含量均明显低于各组间治疗前及对照组治疗后,差异具有统计学意义(P＜0.05);观察组治疗后CD4+、CD4+/CD8+表达高于治疗前及对照组治疗后,而CD8+明显低于治疗前及对照组治疗后,差异具有统计学意义(P＜0.05);两组治疗后Fas、FasL表达均低于各组间治疗前,差异具有统计学意义(P＜0.05);观察组治疗后C-反应蛋白水平低于各组间治疗前及对照组治疗后,差异具有统计学意义(P＜0.05);两组均无明显不良反应发生.结论:溃疡性结肠炎患者应用双歧杆菌四联活菌片联合奥沙拉嗪治疗临床疗效明显,双歧杆菌四联活菌片可使CD4+/CD8+比值恢复正常范围,经逆转Fas/FasL表达异常,而诱导淋巴细胞凋亡,故而具有重要临床研究价值.     

芍药汤加味联合奥沙拉秦钠治疗湿热内蕴型活动期溃疡性结肠炎对照研究

[目的]观察芍药汤加味联合奥沙拉秦钠治疗湿热内蕴型活动期溃疡性结肠炎疗效。[方法]将40例门诊患者随机数字表法分为两组。对照组20例奥沙拉秦钠1g/次,2次/d,饭后口服。治疗组20例奥沙拉秦钠治疗同时加用芍药汤加味(白芍20g,黄芩15g,黄连9g,黄柏15g,大黄3g,槟榔9g,当归12g,木香12g,肉桂3g,甘草6g)1剂/d。均治疗6周,随访12月判定疗效。[结果]治疗组完全缓解12例,有效8例,无效0例,总有效率100.00%。对照组完全缓解10例,有效7例,无效3例,总有效率85.00%。临床疗效治疗组优于对照组(P<0.05),主要症状及结肠镜检有效率治疗组优于对照组(P<0.05)。[结论]芍药汤加味联合奥沙拉秦钠治疗湿热内蕴型活动期溃疡性结肠炎疗效优于单用奥沙拉秦钠,值得推广。     

奥沙拉秦钠残留溶剂测定方法的改进

目的：改进奥沙拉秦钠残留溶剂的测定方法。方法：采用气相色谱顶空进样,色谱柱为DB-624弹性毛细管柱,柱温：110℃;检测器：FID;进样口温度：200℃,检测器温度：250℃;载气：N2;流速：3.0 ml·min-1;分流进样;分流比：1∶1,以水为溶剂测定二氯乙烷,三氯甲烷残留量。结果：两种残留溶剂能够完全分离,二氯乙烷,三氯甲烷分别在0.25~2.52（r=0.999 5）,2.28~22.84μg·ml-1（r=0.999 5）范围内,线性关系良好,平均回收率分别为98.4%,99.5%,RSD分别为1.14%和1.78%（n=9）。最低检出限分别为0.02,0.06μg·ml-1。结论：该顶空气相色谱法准确可靠,灵敏度高,可用于奥沙拉秦钠中残留溶剂的测定。