肠炎康联合美沙拉嗪治疗溃疡性结肠炎

目的:比较肠炎康联合美沙拉嗪与美沙拉嗪治疗溃疡性结肠炎的疗效,为临床治疗溃疡性结肠炎提供合理用药的建议.方法:将吉林大学第一医院2010年6月-2011年5月门诊收治的溃疡性结肠炎患者90例,随机分为治疗组45例和对照组45例,分别接受肠炎康联合美沙拉嗪与美沙拉嗪的治疗方法,用药后对两组的治疗有效率、结肠镜下形态变化及C-反应蛋白及血沉等进行比较,评价其疗效及安全性.结果:两组治疗后的有效率、结肠镜下形态变化比较均具有统计学意义(P＜0.05).结论:肠炎康联合美沙拉嗪的疗效优于美沙拉嗪,值得临床推广应用.     

Design of a colonic delivery system based on cationic polymethacrylate (Eudragit E100)-mesalamine complexes

In this work, the design and evaluation of a colonic drug delivery system containing mesalamine (M) is presented. The main goal was to enable M to reach the first part of the colon, where the drug could then be released. To facilitate this, a tablet core was coated with two thin layers. The first compounded by chitosan, which was responsible for core protection in the small intestine until it reached the colon. Once at the colon, microbiological enzymatic activity of the caecal content would degrade the Ch layer, thus triggering drug release. The second layer, the outer one, was compounded with Eudragit L100 (EL), with its function being to avoid the dissolution of the Ch-covered core along the gastro intestinal tract (GIT). In order to achieve a modulated drug release, carbomer P934 (1%) was also included. Dissolution studies showed that the formulation seemed to behave as predicted. The amount of M released from the coated tablet was less than 10% at pH?=?1.2 and 6.8. However, when the coated tablet was evaluated in a medium with a caecal content of pH?=?7.4, the M delivery was immediately triggered owing to enzymatic activity of the microflora. In this medium, ～ 60% of M was released in a period of 3?h. Although these results are promising, further studies are still necessary to evaluate the possible in vitro/in vivo correlations.     

Film coated tablets (ColoPulse technology) for targeted delivery in the lower intestinal tract: Influence of the core composition on release characteristics

The design of a film coating technology which allows a tablet to deliver the drug in the ileocolonic segment would offer new treatment possibilities. The objective is to develop a platform technology that is suitable for a broad range of drug compounds. We developed a coated tablet with a delayed, pulsatile release profile based on a pH-sensitive coating technology (ColoPulse). The production process was validated, and the effect of core composition on the in vitro release and water uptake investigated. The release profile of the standard tablet core composition, based on the use of cellulose as a filler, was independent of the coat thickness in a range of 9.0–13.2?mg/cm². The release profile of a coated tablet was strongly influenced when cellulose was partly replaced by the model substance glucose (loss of sigmoidal release), citric acid (stabilization), sodium bicarbonate (destabilization) or sodium benzoate (destabilization). The film coating takes up water when below the pH-threshold. However, this did not cause early disintegration of the coating. The ColoPulse technology is successfully applied on tablets. The in vitro release characteristics of the coated tablets are influenced by the composition of the core.     

结肠用美沙拉秦壳聚糖胶囊的体外释药研究

 目的制备美沙拉秦(5-氨基水杨酸，5-ASA)结肠靶向给药胶囊，并评价其体外释药性能。方法将5-ASA装于壳聚糖胶囊中，再以邻苯二甲酸羟丙基甲基纤维素(HPMCP)包裹胶囊，以紫外分光光度法测定其在pH1.2盐酸溶液及pH6.8磷酸缓冲液中的体外释放性能。将荧光素钠(FS)作为模型化合物在相同条件下进行实验，以激发波长470 nm，发射波长513 nm荧光检测其在模拟大肠液中的体外释放性能。用扫描电镜法评价壳聚糖胶囊在模拟大肠液中的降解作用。结果 载药壳聚糖胶囊在pH1.2盐酸溶液及pH6.8磷酸缓冲液中药物累积释放量6 h内不大于10%，而在模拟大肠液中，4 h释药基本完全。电镜扫描表明，在盲肠内容物中壳聚糖具有明显降解作用。结论 用HPMCP包膜的壳聚糖胶囊具有潜在的结肠靶向释药效果。     

花生四烯酸代谢物在湿热型溃疡性结肠炎大鼠的表达与调节

目的:探讨花生四烯酸(AA)代谢物在湿热型溃疡性结肠炎(UC)大鼠发病的作用以及黄芩汤的调节。方法:采用高脂高糖饲料结合人工气候箱法造成大鼠湿热,使用三硝基苯磺酸灌肠造成湿热型UC模型;将造模大鼠分为模型组(n=12)、黄芩汤治疗组(n=13)及美沙拉嗪组(n=12)。治疗两周后用ELISA法检测大鼠前列腺素E2(PGE2)、血小板活化因子(PAF)、白三烯B4(LTB4)及环氧合酶-2(COX-2)含量;检测甘油三酯(TG)及总胆固醇(CH)含量并计算粪便脂肪球数量从而反映湿热程度;对结肠进行肉眼组织学评分从而评价UC的严重程度;将AA代谢物与以上湿热型UC指标进行相关性分析。结果:与空白组(n=12)比较,造模组血清及结肠PGE2、PAF、LTB4及COX-2含量明显升高(P<0.05);治疗后黄芩汤组的PGE2及LTB4均显著低于美沙拉嗪组(P<0.05),但PAF及COX-2无组间差异。湿热指标方面,治疗后黄芩汤组血脂及粪便脂肪球数量均显著低于美沙拉嗪组(P<0.05);UC方面,黄芩汤及美沙拉嗪组的组织学评分无统计学差异。相关性分析显示组织评分与AA代谢物、血脂及粪便脂肪球均呈显著正相关性(r>0.930,P<0.01)。结论:AA代谢物在湿热型UC大鼠血清及结肠明显升高,且与反映湿热的血脂及粪便脂肪球、与反映UC程度的组织学评分均呈正相关性;黄芩汤对代谢物PGE2、LTB4及对湿热指标的调节作用优于美沙拉嗪。     

Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy

Background and purpose:

5-aminosalicylate (5-ASA) raises levels of 6-thioguanine nucleotides (6-TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN – 6-thioguanosine mono-, di- and triphosphate (6-TGMP, 6-TGDP, 6-TGTP) – and of 6-methylmercaptopurine ribonucleotides (6-MMPR) after 5-ASA are not known.

Experimental approach:

Effects of increasing 5-ASA doses on AZA metabolites were investigated prospectively in 22 patients with inflammatory bowel disease in 4-week study periods. Patients started with 2 g 5-ASA daily, and then were increased to 4 g daily and followed by a washout period. Thiopurine doses remained unchanged throughout the entire study. Levels of 6-TGMP, 6-TGDP, 6-TGTP and 6-MMPR as well as of 5-ASA and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) were determined each study period.

Key results:

Median baseline levels in 17 patients of 6-TGDP, 6-TGTP and 6-MMPR were 52, 319 and 1676 pmol per 8 × 10⁸ red blood cells respectively. After co-administration of 2 g 5-ASA daily, median 6-TGDP and 6-TGTP levels increased but median 6-MMPR levels were unchanged. Increasing 5-ASA to 4 g daily did not affect median 6-TGDP and 6-TGTP levels, but median 6-MMPR levels decreased. After discontinuation of 5-ASA, both 6-TGDP and 6-TGTP levels decreased and median 6-MMPR levels increased. The 6-TGTP/(6-TGDP+6-TGTP)-ratio did not change during the study, but 6-MMPR/6-TGN ratios decreased.

Conclusions and implications:

Individual 6-TGN metabolites increased after addition of 5-ASA, but 6-MMPR-levels and the 6-MMPR/6-TGN ratios decreased. Further studies are needed to decide whether this pharmacokinetic interaction would result in improvement of efficacy and/or increased risk of toxicity of AZA.     

紫榆膏联合锡类散直肠给药治疗热毒炽盛证溃疡性直肠炎的临床疗效观察

[目的]观察紫榆膏联合锡类散直肠给药治疗热毒炽盛证溃疡性直肠炎的临床疗效。[方法]将60例溃疡性直肠炎患者随机分为对照组和治疗组,每组30例,治疗组给予紫榆膏联合锡类散直肠给药治疗,对照组给予美沙拉秦栓纳肛治疗,疗程均为4周。观察两组治疗前后临床疗效、临床症状评分、炎症指标、直肠镜检查评分及药物不良反应。[结果]治疗后,治疗组总有效率为93.33%,对照组总有效率为96.67%,两组总有效率比较,差异无统计学意义（P>0.05）。治疗组治疗后临床症状评分、炎症指标[肿瘤坏死因子（TNF）-α、白细胞介素（IL）-8、IL-10、直肠镜检查评分与治疗前比较,差异有统计学意义（P<0.01）;治疗组各项指标与对照组比较,差异无统计学意义（P>0.05）;与对照组比较,治疗组不良反应发生率较低,差异有统计学意义（P<0.05）。[结论]紫榆膏联合锡类散直肠给药治疗溃疡性直肠炎与美沙拉秦栓相比疗效相当,皆能有效改善患者临床症状,减轻炎症反应,但紫榆膏联合锡类散的不良反应发生率较低,值得在临床上推广应用。     

紫艾汤保留灌肠联合美沙拉嗪治疗远端结肠型溃疡性结肠炎的疗效观察

目的观察紫艾汤保留灌肠联合美沙拉嗪治疗远端结肠型溃疡性结肠炎疗效。方法将68例患者按随机数字表法分为观察组和对照组各34例。对照组美沙拉嗪,4 g/次,4次/d。观察组在对照组基础上联合紫艾汤保留灌肠。连续治疗30 d。观测临床疗效、白介素-8、白介素-10、肿瘤坏死因子-α、白细胞计数、血小板计数。结果治疗后,观察组总有效率(94.12%,32/34)高于对照组(73.53%,25/34)(P<0.05);治疗后,观察组炎性因子改善优于对照组(P<0.05);治疗后,观察组白细胞计数、血小板计数优于对照组(P<0.05)。结论紫艾汤保留灌肠联合美沙拉嗪治疗远端结肠型溃疡性结肠炎,可减轻炎症反应,减轻痛苦,值得推广。     

Pulmonary infiltrates and eosinophilia associated with sulphasalazine administration

A case of blood eosinophilia with pulmonary infiltrates associated with sulphasalazine therapy in a patient with ulcerative colitis is described. These manifestations resolved when sulphasalazine was ceased and recurred with rechallenge. The failure of recurrence after treatment with mesalazine (5-aminosalicylic acid in a sustained release preparation) suggests that sulphapyridine is the component responsible for this reaction.     

布拉氏酵母菌散联合美沙拉嗪肠溶片治疗中轻度溃疡性直乙状结肠炎的疗效观察

[目的]探究布拉氏酵母菌散联合美沙拉嗪肠溶片治疗中轻度溃疡性直乙状结肠炎的临床疗效。[方法]回顾性分析52例给予美沙拉嗪肠溶片治疗(对照组)及52例布拉氏酵母菌散联合美沙拉嗪肠溶片治疗(观察组)的中轻度溃疡性直乙状结肠炎患者的临床资料。记录2组临床疗效、结肠黏膜炎症改善情况及治疗12周后复发情况,比较2组治疗前及治疗4周后炎性活动指标(血沉、C反应蛋白)及肠黏膜屏障功能障碍指标(内毒素、D-乳酸)的差异。[结果]观察组临床疗效及结肠黏膜炎症改善情况明显优于对照组(P<0.05),且治疗12周后复发率明显低于对照组(P<0.05)。治疗4周后,2组炎性活动指标(血沉、C反应蛋白)、肠黏膜屏障功能障碍指标(内毒素、D-乳酸)均较治疗前降低(P<0.05),且观察组低于对照组(P<0.05)。[结论]布拉氏酵母菌散联合美沙拉嗪肠溶片治疗中轻度溃疡性直乙状结肠炎临床疗效显著,不仅能减轻机体炎性活动度,还能提高肠黏膜屏障功能,对降低复发风险也有积极意义。