超声波作用下合成奥沙拉秦

目的:合成奥沙拉秦.方法:以水杨酸为原料,在超声波作用下合成目标化合物.结果与结论:总收率为31.2%,反应时问为4.5 h,与文献相比提高了产率,缩短了反应时间.     

柳氮磺吡啶与奥沙拉嗪治疗溃疡性结肠炎的临床疗效研究

目的比较柳氮磺吡啶和奥沙拉嗪治疗溃疡性结肠炎的疗效及安全性。方法将84例溃疡性结肠炎患者,随机分为奥沙拉嗪组和柳氮磺吡啶组各42例,观察两组疗效和不良反应。结果奥沙拉嗪组组患者的总有效率80.95%显著高于柳氮磺胺吡啶组69.05%,差异有统计学意义(P<0.05)。奥沙拉嗪组不良反应发生率为4.76%,低于柳氮磺胺吡啶组的14.29%,差异有统计学意义(P<0.05)。结论奥沙拉嗪是治疗溃疡性结肠炎安全、有效的药物,不良反应少,值得临床推广。     

美沙拉嗪肠溶缓释颗粒剂的大鼠药动学及胃肠道分布研究

目的 评价新型制剂美沙拉嗪肠溶缓释颗粒剂在SD大鼠体内的药动学以及在胃肠道的分布情况,了解该制剂临床前药动学特征及胃肠道分布特征。方法 采用大鼠口服给药,测定其血药浓度和胃肠道残留浓度;以美沙拉嗪缓释颗粒剂（市售制剂）为参照,评价美沙拉嗪肠溶缓释颗粒剂（自研制剂）在大鼠体内吸收和消除过程、相对生物利用度、药物在胃肠道分布情况。结果 美沙拉嗪肠溶缓释颗粒剂在大鼠体内,与美沙拉嗪缓释颗粒剂以美沙拉嗪表征的相对生物利用度为(90.62±9.36)%。美沙拉嗪肠溶缓释颗粒剂口服给药后在2~8 h时间段,药物在胃部存在高浓度分布,随着时间的推移逐步进入并残存于空肠、回肠和结肠,6~12 h后在结肠达到高浓度分布,其结果有助于美沙拉嗪药物的体内吸收,以及缓释颗粒剂在作用部位的定点释放与发挥疗效。结论 美沙拉嗪肠溶缓释颗粒剂吸收和消除过程基本呈线性动力学特征,药动学参数与市售制剂无显著性差异,且在胃肠道有一定流动性,包衣对消化液耐受性好,胃肠道分布特征有利于药物的体内吸收和作用部位的定点释放。     

奥硝唑联合美沙拉嗪治疗溃疡性结肠炎的疗效观察

目的探讨奥硝唑联合美沙拉嗪治疗溃疡性结肠炎的疗效。方法选取2011年9月—2013年7月本院收治的55例溃疡性结肠炎患者,随机分为美沙拉嗪组（28例）、药物联用组（27例）,美沙拉嗪组给予美沙拉嗪治疗,药物联用组给予奥硝唑＋美沙拉嗪治疗,比较美沙拉嗪组和药物联用组的疗效。结果美沙拉嗪组有效率为64.3%（18/28）,药物联用组为92.6%（25/27）,两组有效率比较,差异有统计学意义（P〈0.05）。两组复发率比较,差异有统计学意义（P〈0.05）。结论奥硝唑联合美沙拉嗪治疗溃疡性结肠炎的疗效很好,能提高溃疡性结肠炎者的治愈率,降低溃疡性结肠炎的复发率。     

不同微生态制剂联合奥沙拉嗪对轻中度溃疡性结肠炎的治疗作用

目的:观察不同微生态制剂联合奥沙拉嗪对轻中度溃疡性结肠炎(慢性复发型,活动期)的临床疗效。方法:采用随机、对照设计,将60例轻中度溃疡性结肠炎患者随机分为3组,即金双歧组(金双歧+奥沙拉嗪)、美常安组(美常安+奥沙拉嗪)、奥沙拉嗪组(单纯使用奥沙拉嗪),每组20例。比较3组患者治疗前后临床症状评分、结肠炎症评分、结肠镜下分级评分及分析粪便菌群,疗程为24个月,随访48个月。粪便菌群分析设正常对照组。结果:金双歧组、美常安组的临床症状评分、结肠炎症评分、结肠镜下分级评分及粪便菌群分析情况均明显优于奥沙拉嗪组,且金双歧组优于美常安组。随访48个月,金双歧组未见复发,美常安组有3例复发,奥沙拉嗪组有18例复发。结论:微生态制剂联合奥沙拉嗪治疗溃疡性结肠炎的疗效明显优于单纯使用奥沙拉嗪。     

奥沙拉嗪与柳氮磺吡啶治疗溃疡性结肠炎的临床对比研究

目的比较奥沙拉嗪和柳氮磺吡啶(SPAP)治疗溃疡性结肠炎(UC)的有效性及安全性。方法将来74例UC患者,随机分为观察组和对照组各37例,治疗组应用奥沙拉嗪,对照组使用SPAP治疗,观察两组疗效和不良反应。结果治疗组患者的总有效率显著高于对照组,差异有统计学意义(P<0.05);治疗组不良反应发生率为5.41%,低于观察组的27.03%,差异有统计学意义(P<0.05)。结论奥沙拉嗪是治疗UC安全、有效的药物,不良反应少,值得临床推广。     

药物化学实验合成美沙拉嗪的方法改进

目的探讨药物化学实验合成美沙拉嗪的改进方法。方法通过改进实验方法,以水杨酸为原料,控制硝酸硝化反应,在酸性条件下以锌粉和铁粉混合交替添加的办法进行硝基还原。结果第一步反应得到5-硝基水杨酸收率为65%,美沙拉嗪的总收率为39%。结论改进后的合成方法简单,实验结果可靠,便于学生学习和掌握,可提高教学效果和质量。     

三种氨基水杨酸制剂治疗溃疡性结肠炎的安全性和有效性研究

目的观察美沙拉嗪、奥沙拉嗪和柳氮磺吡啶治疗溃疡性结肠炎的临床疗效和不良反应。方法选择120例轻中度溃疡性结肠炎患者,随机分为美沙拉嗪组（n=40）、奥沙拉嗪组（n=39）和柳氮磺吡啶组（n=41）,分别接受上述三种药物治疗。美沙拉嗪组和奥沙拉嗪组患者口服药物剂量均为每次1．0g,每日3次;而柳氮磺吡啶组患者服用剂量为每次1．0g,每日4次。治疗12周后观察治疗疗效和不良反应发生情况。结果美沙拉嗪组、奥沙拉嗪组和柳氮磺吡啶组临床有效率分别为30．0％、28．2％和51．2％,总有效率分别为75．0％、76．9％和92．7％。柳氮磺吡啶组疗效优于美沙拉嗪组、奥沙拉嗪组（P〈0．05）。结论与美沙拉嗪、奥沙拉嗪相比,柳氮磺吡啶治疗溃疡性结肠炎有效性更高,但不良反应发生率稍高。     

美沙拉嗪联合奥硝唑治疗溃疡性结肠炎的临床观察

目的观察美沙拉嗪联合奥硝唑治疗溃疡性结肠炎的临床疗效。方法 62例溃疡性结肠炎患者随机分为观察组和对照组两组,每组31例,对照组采用美沙拉嗪灌肠治疗,观察组在对照组的基础上加服奥硝唑。结果观察组总有效率为93.5%,显著高于对照组的83.9%,差异有统计学意义(P<0.05)。结论美沙拉嗪联合奥硝唑治疗溃疡性结肠炎效果好于单用美沙拉嗪,值得临床推广应用。     

异嗪皮啶在大鼠体内的药物动力学研究及其组织分布

摘要：目的:建立HPLC方法对异嗪皮啶在大鼠体内的药物动力学及组织分布进行研究。方法:以4-羟基香豆素为内标,通过HPLC检测血浆样品和各组织样品中的药物的含量:采用Diamonsil C18色谱柱（150×4.6 mm,5μm）;流动相为乙腈-0.1%磷酸（20∶80）;紫外检测波长为344 nm;柱温设定在30℃;流速为1.0 ml·min-1。并利用药动学软件3p97计算各药物动力学参数。结果:本法灵敏度较高,所制备的样品中杂质干扰较小,而且操作简便。异嗪皮啶主要药动学参数:tmax=（0.27±0.02）h,Cmax=（7.52±0.47）μg·ml-1,t1/2=（4.35±0.73） h,AUC0→12=（13.74±1.01）μg·ml-1·h,CL/f（s）=（1.89±0.07） mg·kg·h-1(μg·ml-1),V/f（c）=（1.37±0.04）(mg·kg-1)/(μg·ml-1)。异嗪皮啶给药30 min后体内分布较广,以脑中浓度最高,约为肺中浓度的3倍;脾中含量次之,心、肝、肺、肾中含量相当;120 min后药物浓度均明显降低。结论:异嗪皮啶C-t曲线为一室模型;异嗪皮啶在大鼠体内分布较广,但浓度普遍较低,给药120 min后药物浓度均明显降低。     

瑞巴派特保留灌肠治疗溃疡性结肠炎临床疗效

目的：观察瑞巴派特保留灌肠治疗溃疡性结肠炎（uc）的临床疗效及安全性。方法：随机将128例UC患者分成A、B两组,两组均给与奥沙拉嗪常规治疗,A组患者用瑞巴派特保留灌肠,B组用复方锡类散液保留灌肠治疗。结果：A组患者有效率（93．75％）明显高于B组（81．25％）（P〈0．05）,未见明显不良反应。结论：瑞巴派特保留灌肠能有效保护UC患者结肠黏膜并促进溃疡愈合,不良反应少,联合奥沙拉嗪能有效治疗溃疡性结肠炎。     

那格列奈合成工艺改进

目的:改进那格列奈的合成工艺以提高产率并促进工业化生产。方法:分别从反应试剂、催化剂及晶型转型方面进行改进,即在顺反转化中用氢氧化钠替代文献中的氢化钠,在氯化反应中用氯化亚砜代替文献中的三氯化磷或五氯化磷;以RuNiAlC催化剂代替文献中的PtO2或Raney Ni;在H晶型转型中采用低温粉碎得微粒晶种以晶种引导结晶的方法获得H型晶体,并对改进方法所制成品的晶型结构进行表征及计算产率。结果:晶型表征结果证实产品为那格列奈H型晶体,产率达72%,高于文献报道的50%。结论:改进后工艺的产率升高,适合工业化生产。     

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。     

Technetium‐99 m labeling and evaluation of olsalazine: a novel agent for ulcerative colitis imaging

Ulcerative colitis is a chronic disease having a regressive nature. Commonly used diagnostic methods have the disadvantage to be invasive, time‐consuming, and expensive. Therefore, a new sensitive method for the detection and monitoring of disease activity is urgently needed in clinical practice. In the current investigation, radio complexation of olsalazine with technetium‐99m, its characterization, and optimization of the labeling conditions were explored. Optimum radiochemical yield of ^99mTc‐olsalazine (97.6% ± 1.8%) was obtained via direct complexation with technetium‐99m (~200 MBq) in the presence of stannous chloride dihydrate (100 µg) as reducing agent at pH 6. It was observed that the complex showed significant in vitro stability in serum at 37°C for more than 11 h. The computer‐generated optimized geometries of the ^99mTc‐olsalazine were reported, and biodistribution studies were carried out using chemically and microbiologically mice‐induced ulcerative colitis models. The tracer showed a good localization in both models and was excreted mainly via liver and to some extent via kidney. Imaging can be performed at 1–2 h post‐injection; at that time, the background activity has cleared, and the activity is concentrated in the target site. All the gathered biological data supported the usefulness of ^99mTc‐olsalazine as a potential imaging agent for ulcerative colitis.     

Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis

Aim:

To compare the efficacy and tolerability of olsalazine sodium with enteric-coated mesalazine in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis.

Patients and methods:

Patients with mild to moderate active ulcerative colitis were randomized to receive either olsalazine sodium, 3 g/day (n = 88), or mesalazine, 3 g/day (n = 80), for up to 12 weeks.

Results:

Of the patients treated with olsalazine sodium, 52.2% achieved endoscopic remission, compared with 48.8% of patients treated with mesalazine. This difference was not significant (P = 0.67). There was a non-significant trend for patients with left-sided colitis or a more severe endoscopic grade to achieve remission if they were treated with olsalazine sodium than if they were treated with mesalazine. Both treatments were comparable with respect to clinical activity index and an investigator’s global assessment. Seventy patients reported one or more adverse events; adverse events were seen in 45% of olsalazine sodium-treated patients and in 36% of mesalazine-treated patients. Eleven patients treated with olsalazine sodium and nine patients treated with mesalazine withdrew from the study because of adverse events. One patient treated with olsalazine sodium compared with two treated with mesalazine stopped treatment because of diarrhoea. Serious adverse events occurred in three patients treated with olsalazine sodium and in four treated with mesalazine.

Conclusion:

Therapeutic effectiveness and tolerance to the treatment did not differ between olsalazine sodium, 3 g/day, and mesalazine, 3 g/day, in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis within 12 weeks of treatment.

     

Olsalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease.

Olsalazine (sodium azodisalicylate; azodisal sodium) is an anti-inflammatory agent designed to deliver its active moiety, mesalazine (5-aminosalicylic acid; mesalamine), to the colon while avoiding the adverse effects associated with the use of a sulfapyridine carrier. As a prodrug, olsalazine is an effective oral treatment for both active ulcerative colitis and for maintenance of disease remission and may possibly be of benefit in patients with Crohn's colitis. Findings from both short and long term noncomparative and comparative studies demonstrate that olsalazine 1 to 3g daily in divided doses improves clinical signs and symptoms of colitis in approximately 60 to 80% of patients with acute ulcerative colitis of mild to moderate severity. This improvement rate was similar to that obtained with sulfasalazine. Lower doses of olsalazine, usually 1g daily in divided doses, also maintained remission in patients with chronic ulcerative colitis. While olsalazine effectively delivers mesalazine to the colon, the prodrug itself increases net luminal water secretion and accelerates gastrointestinal transit of a meal. The resulting diarrhoea (occurring in approximately 17% of patients and resulting in withdrawal from therapy in 6% of patients) is distinguishable from that associated with inflammatory bowel disease by the high water content and the absence of blood. Olsalazine-induced diarrhoea usually occurred soon after initiation of olsalazine therapy or dosage increase, was more frequent with higher doses and was usually transient. Dosage reduction, increases in frequency of dosing and concomitant administration with food reduced the severity in many patients with persistent olsalazine-induced diarrhoea. With the exception of diarrhoea, olsalazine was generally well tolerated. Fewer than 14% of patients allergic to or intolerant of sulfasalazine had similar reactions to olsalazine. Olsalazine appears to be a suitable therapy for the treatment of first attacks as well as acute exacerbation of mild to moderate acute ulcerative colitis, and for the maintenance of remission in patients with chronic ulcerative colitis.     

Determination of olsalazine sodium in pharmaceuticals by differential pulse voltammetry

The electrochemical oxidation of olsalazine sodium was investigated by cyclic, linear sweep, differential pulse and square wave voltammetry using glassy carbon disc electrode in different buffer systems. Best results were obtained for the determination of olsalazine using the differential pulse voltammetric technique in phosphate buffer at pH 7.0. The electroactive species exhibits a diffusion-controlled voltammetric wave and its differential pulse peak current shows a linear dependence on olsalazine concentration in the range between 2 x 10(-6) M and 2 x 10(-4) M. This relationship has been applied to the determination of olsalazine in commercial capsule dosage forms. The recovery study shows good accuracy and precision for the assay developed. A UV spectrophotometric assay is also reported for comparison.     

正交试验优选氧化苦参碱毫微粒的制备工艺

目的:优选氧化苦参碱毫微粒的制备工艺。方法:采用正交试验法,以包封率和载药量为评价指标,以氧化苦参碱的用量、聚氰基丙烯酸正丁酯的用量、介质的pH值、混合时间为因素优选制备工艺。结果:最佳优化条件为160mg的氧化苦参碱及80mg的聚氰基丙烯酸正丁酯在pH2.0的条件下混合3h,载药量为(16.90±0.25)%,包封率为(72.75±0.19)%。结论:优选处方和制备工艺稳定可行,可为开发氧化苦参碱的新剂型提供参考。     

国产奥沙拉秦钠胶羹治疗溃疡性结肠炎149例

目的 验证国产奥沙拉秦钠胶囊治疗轻、中度溃疡性结肠炎（活动期）的治疗效果,比较国产奥沙拉秦钠胶囊与水杨酸柳氨磺胺吡啶（ＳＡＳＰ）对轻、中度溃疡性结肠炎（活动期）的疗效和不良反应。方法 采用多中心随机双盲对照验证１０７例轻、中度溃疡性结肠炎（活动期）的疗效和不良反应,同时,治疗４２例作为开放组,疗程为８周。结果 国产奥沙拉秦钠胶囊的总有效率达 ８４．６％,双盲组中,其临床完全缓解率、内镜完全缓解率和组织学完全缓解率在治疗８周后均比治疗前明显改善,分别各自达７５．００％,３４．６２％,５５．７７其疗效与开放组和对照组ＳＡＳＰ均类同。国产奥沙拉秦钠胶囊不良反应主要为腹泻。结论 国产奥沙拉秦钠胶囊治疗活动期轻、中度溃疡性结肠炎有效,其结果与ＳＡＳＰ相当,主要不良反应为腹泻,宜与控制腹泻药物合用。     

正交试验优选杏香兔耳风总黄酮提取工艺

目的:优选杏香兔耳风总黄酮的提取工艺。方法:以芦丁为对照,以溶剂用量、提取次数、浸泡时间和提取时间为考察因素,以总黄酮转移率为指标,采用正交试验优选最佳提取工艺。结果:最佳提取工艺为用pH8的氨水配制的50%乙醇溶液为提取溶剂,分别以10、10、8、8倍量回流提取4次,每次1h;总黄酮转移率为84.97%。结论:该提取工艺合理、简单,可用于大规模生产。