5—氨基水杨酸结肠定位释药包衣片的研制

目的：构建口服5－氨基水杨酸结肠定位释药系统。方法：以延时性和pH值依赖性为结肠控释依据,采用多层薄膜包衣法制备结肠定位释放片剂,采用γ射线显影法,考察包衣片在狗体内的释药部位与释药时间。结果：研制的口服5－氨基水杨酸结肠定位释药片剂制备工艺简单,药物释放稳定,在狗的升结肠崩解释药。结论：构建的5－氨基水杨酸的口服结肠定位释药系统具有进一步开发应用前景。     

5-氨基水杨酸的结肠靶向释药系统

5-氨基水杨酸是目前治疗炎症性肠病（inflammatory bowel disease,IBD）的首选药物,但因其口服后主要被小肠吸收,导致结肠局部浓度低而降低药效。结肠靶向给药系统可以使药物直达病变部位,提高药效,因而成为研究热点。本文就几种结肠靶向给药系统进行讨论,以望为日后IBD治疗的研究提供参考。     

5-氨基水杨酸结肠释药包衣片剂的制备和体外释放

用治疗结肠炎的药物5-氨基水杨酸作为模型药,用直链淀粉/正丁醇复合物及乙基纤维素作为包衣材料,制备了5-氨基水杨酸结肠释药包衣片,并进行了体外释放实验等。结果证实包衣材料选用适当的比例,可心使药物在结肠定位靶向释放。     

康复新结肠定位滴丸在犬体内结肠定位释药的研究

目的 考察康复新结肠定位滴丸在体内结肠的定位释放性能.方法 用γ-射线闪烁照相法考察包衣滴丸在犬体内的定位释药部位与释药时间.结果 包衣滴丸在犬的横结肠和降结肠崩解释药.结论 康复新结肠定位包衣滴丸具有结肠定位的释药性能.     

5—氨基水杨酸与其结肠靶向制剂

溃疡性结肠炎和节段性回肠炎(Crohn病)等炎症性肠道疾病是一种较为常见的慢性、复发性疾病,其发病率在西方国家较高,在我国也有增高的趋势。5-氨基水杨酸(5-aminosalicylic acid.5-ASA )是治疗这类疾病的主要药物之一,在国外已有多种制剂上市,但国内目前尚无生产,有关该药的理化性质和制剂特征的文献报道也极少。由于5-ASA需到达结肠后局部发挥作用,因此其口服制剂具有特殊性。本文介绍5-ASA的性状、作用特点及国外常用的结肠靶向制剂。     

结肠定位释药双氯芬酸钠包衣片体内外相关性

目的研制时间依赖型口服结肠定位释药双氯芬酸钠包衣片。方法用释放度测定法研究双氯芬酸钠包衣片体外释放行为 ,用HPLC法测定包衣片在家犬体内的血药浓度 ,并计算出相关参数 ,进行体内外相关性考察。结果体外平均延迟释放时间为 4～ 5h时 ,体内平均时滞为 3～ 6h ,达到预期结果。结论本文研制的双氯芬酸钠片有进一步开发的价值     

5-氨基水杨酸制剂研究现状及展望

5-氨基水杨酸是临床治疗溃疡性结肠炎的主要药物,为促进该产品更好地研发与应用,本文就5-ASA目前已上市品种及正处于研发的制剂设计进行较详细的整理,并探讨5-氨基水杨酸临床最佳的制剂形式。     

5-氨基水杨酸结肠定位柱塞型脉冲胶囊的制备与体外释放

目的:制备5-氨基水杨酸结肠定位柱塞型脉冲胶囊并对其体外释药行为进行评价。方法:用灌注法制备非渗透性胶囊体,粉末直接压片法压制柱塞片,湿法制粒法制备含药速崩片,将速崩片与柱塞片密封于非渗透性胶囊体内制备脉冲胶囊,考察影响释药时滞的各种因素。结果:胶囊在体外呈明显的脉冲释放,释药时滞随柱塞片中高酯果胶-乳糖或羟丙甲纤维素-低酯果胶比例的增加而增加,具有相同处方柱塞片的脉冲胶囊在模拟结肠溶出介质中释药时滞明显缩短,当高酯果胶-乳糖为4∶6和6∶4,低酯果胶/羟丙甲纤维素为9.5∶0.5和9∶1时,可达到结肠定位所需的4~5h释药时滞。结论:调节柱塞片处方组成可获得具有适当释药时滞的脉冲胶囊,以满足结肠定位释药的目的。     

5-氨基水杨酸pH依赖-菌群触发型结肠定位给药系统的体外释放性能

目的研究5-氨基水杨酸（5-ASA）pH依赖-菌群触发型结肠定位给药系统的体外释放性能。方法将5-ASA装于以瓜尔豆胶和Eudragit S 100包膜的胶囊中,采用Diamonsil TM-C₁₈（250mm×4.6mm,5μm）色谱柱,柱温25℃,流速1.0mL·min^-1,检测波长为240nm,测定其在pH 1.2 HCl、pH6.8和7.4 PBS溶液中的体外释放性能。结果 5-ASA胶囊的3批样品在pH 1.2 HCl、pH 6.8 PBS溶液中几乎不释药,在pH 7.4 PBS溶液中有释药。增重34%样品在pH 7.2 PBS和pH 7.2 PBS+β-甘露聚糖酶的溶液中,释放无明显差异;而增重44%样品有差异。结论用瓜尔豆胶和Eudragit S 100包膜的5-ASA胶囊具有良好的结肠定位释药效果。     

5-氨基水杨酸甘氨酸盐在胃肠道内的稳定性研究

目的 研究5-氨基水杨酸甘氨酸盐(5-ASA-Gly)在大鼠胃肠道中的稳定性。方法 以SD大鼠为实验动物,采用高效液相色谱法考察了5-ASA-Gly在体内外胃、小肠环境下及大鼠盲肠内容物中5-氨基水杨酸(5-ASA)的分布情况。结果 5-ASA-Gly在胃和小肠环境下相当稳定,未释放出5-ASA;而在与人体结肠部位细菌环境非常类似的大鼠盲肠内容物中则有5-ASA出现。结论 5-ASA-Gly经盲结肠相关菌丛或酶丛的作用释放出游离药物5-ASA,大大降低了5-ASA的全身吸收,可作为一种有希望的结肠定位释药特定性前体药物加以研究与开发。     

反相高效液相色谱法测定5—氨基水杨酸相关物质、原料含量及缓释片含量

目的：应用高效液相色谱法测定5-氨基水杨酸原料药及缓释片的含量。方法：反相高效液相色谱法,选择KromasilC18柱,以甲醇-磷酸盐缓冲液（35：65）为流动相,流速1ml.min^-1,检测波长254nm。结果：浓度与峰高的回归方程为Y=395.36 17.308X,相关系数r=0.9994,线性范围83.71-837.12ug.ml^-1。精密度RSD≤1.34%。辅料对制剂的含量测定无干扰,平均回收率99.25%,RSD=0.65%。结论：测定方法简便、准确、灵敏度高。     

The Effect of Meal Composition on the Gastrocolonic Response: Implications for Drug Delivery to the Colon

The response of the colon to eating, the gastrocolonic response (GCR), may have important implications for the design of drug dosage forms for selective delivery to the colon. Therefore, the effect of meal composition on the GCR and its relation to the transit of non-disintegrating tablets has been investigated. Eight healthy male volunteers each received 5 × 6-mm radiolabeled nondisintegrating tablets, and the transit was followed using a gamma camera. When the tablets reached the ileocolonic region, each volunteer received a test meal (1000 kcal) containing 70% carbohydrate, 15% fat, and 15% protein. The subsequent movement of the tablets was then monitored. The study was repeated using a 70% fat meal and a 70% protein meal, so that the effects of a high-carbohydrate, a high-fat, and a high-protein meal on the GCR could be compared. The incidence of GCRs was similar after all meals. Thus, there appeared to be no effect of meal composition on the movement of the tablets into the colon. This implies that the ingestion of food may not necessarily stimulate the passage of material across the ileocecal junction and that other factors may also be involved.     

The Use of Scintigraphy to Provide 'Proof of Concept' for Novel Polysaccharide Preparations Designed for Colonic Drug Delivery

Purpose. The aim of the present study was to provide 'proof of concept' data in man for novel polysaccharide preparations designed for colonic drug delivery using gamma scintigraphy. Methods. Two placebo calcium pectinate matrix tablet formulations were studied: one contained calcium pectinate and pectin (CaP/P) and was designed to rapidly disintegrate in the ascending colon, the other contained calcium pectinate and guar gum (CaP/GG) and was designed to disintegrate more slowly, releasing its contents throughout the ascending and transverse colon. Both formulations were enteric coated in order to protect them from the stomach. Ten healthy volunteers received either a CaP/P or CaP/GG tablet, in a randomised cross-over study. Transit and disintegration of the radiolabelled formulations was followed by gamma scintigraphy. Rat studies were conducted in order to verify that the expected colonic degradation of the polysaccharide formulations was as a consequence of bacterial enzyme attack. Results. Thein vivo clinical study confirmed the results obtained in the rat and bench in vitro fermentation models; complete tablet disintegration for Formulation CaP/GG appeared to be slower than that of Formulation CaP/P and the time and the location of complete tablet disintegration was more reproducible with Formulation CaP/P compared to Formulation CaP/GG. Conclusions. These results provide 'proof of concept' data for the use of calcium pectinate preparations for drug delivery to the colon and highlight the value of scintigraphy in focusing the development strategy for colonic targeting preparations.     

美沙拉嗪肠溶片剂联合栓剂治疗活动期直乙结肠型溃疡性结肠炎的疗效分析

目的：美沙拉嗪（5-ASA）肠溶片剂联合栓剂治疗活动期直乙结肠型溃疡性结肠炎（UC）的疗效。方法80例活动期直乙结肠型溃疡性结肠炎患者,随机分观察组和对照组,各40例。对照组给予美沙拉嗪肠溶片治疗,观察组给予美沙拉嗪肠溶片联合栓剂治疗。观察两组治疗效果和不良反应。结果接受上述治疗2周时,两组治疗总有效率比较差异无统计学意义（P〉0.05）。治疗4、6、8周时,两组治疗总有效率比较差异具有统计学意义（P〈0.05）。结论口服5-ASA肠溶片与5-ASA栓剂联合使用对我国轻中度UC患者疗效及耐受性良好。     

HPLC测定替硝唑结肠定位肠溶片含量和有关物质检查

目的:建立高效液相色谱法测定替硝唑结肠定位肠溶片中替硝唑含量和有关物质含量。方法:采用ODS柱(4.6 mm×25 cm,10μm),流动相甲醇-水(20:80),流速0.9 mL·min-1,检测波长317 nm,进样量20μL。结果:回归方程为Y=3.987×106X+9.441×104(r=0.9999),线性范围0.025-0.4 mg·mL-1。含量测定回收率为(100.7±0.22)％,(101.8±0.20)％,(101.0±0.05)％。最小检测量为2 ng。结论:此法可用于替硝唑结肠定位肠溶片的有关物质检查和含量测定。     

Application of a Colon Delivery Capsule to 5-Aminosalicylic Acid and Evaluation of the Pharmacokinetic Profile after Oral Administration to Beagle Dogs

Abstract

Pressure-controlled colon delivery capsule (PCC) containing 5-aminosalicylic acid (5-ASA) for the treatment of inflammatory bowel disease (IBD) was prepared and evaluated by an in vivo experiment using beagle dogs. As a reference drug, sulfasalazine (SASP), prodrug of 5-ASA, was used as a plain gelatin capsule preparation. After the oral administration of SASP at the dose of 25.0 mg/kg, the mean time when the plasma 5-ASA concentration reaches to its maximum (Tmax) was 9.0 hr. In the case of 5-ASA administered in PCC, at the doses of 12.5 and 25.0 mg/kg, Tmaxs were 5.3 and 5.3 hr, respectively. Although the time for the first appearance of 5-ASA into the systemic circulation was almost the same value between SASP capsule and PCC containing 5-ASA, longer Tmax was observed from SASP capsule than from PCC. These results suggest that this 5-ASA preparation would be an useful dosage form for the therapy of IBD from the point of avoiding the side effect of sulfapyridine, one of the metabolites of SASP.     

氨基水杨酸药理作用研究进展

水杨酸偶氮磺胺吡啶（SASP）、5-氨基水杨酸（5-ASA）、对氨基水杨酸（4-ASA）是治疗溃疡性结肠炎卓有成效的药物。它们具有共同的氨基水杨酸结构,但三者作用机制不甚相同,确切作用机制不清。SASP、5-ASA抑制炎性介质,而4-ASA对PG、LT无影响。5-ASA清除反应性氧代谢产物作用明显,4-ASA作用较弱。氨基水杨酸影响多种细胞因子（如IL-1,IL-2,IL-6,INF-γ、TNF-α、GM-CSF等）的功能,可能是通过抑制细胞因子与受体结合,或减少一些细胞因子的合成与释放。SASP抑制中性粒细胞脱颗粒、释放溶酶体及一些酶,改变淋巴细胞活性。氨基水杨酸类药物对一氧化氮合成酶、粘附分子及肠道通透性等亦有影响。     

Lack of effect of 5-aminosalicylic acid on platelet aggregation and fibrinolytic activity in vivo and in vitro

Summary We have studied platelet aggregation and fibrinolytic activity in six patients with chronic inflammatory bowel disease treated with 5-aminosalicylic acid (mesalazine).There were no changes in these measurements during normal treatment, i.e. 1.5 g per day with a slow-release formulation, nor after an intravenous dose of 250 mg. Also in vitro tests were negative, in contrast to the inhibition seen with aspirin (acetylsalicylic acid).We conclude that treatment with mesalazine does not constitute a hazard to these patients in regard to prolonged bleeding time caused by an influence on platelet aggregation or fibrinolytic activity.     

HPLC法测定丁酰化-5-氨基水杨酸-果胶共轭物的载药量

目的:建立测定丁酰化-5-氨基水杨酸-果胶共轭物载药量的方法。方法:共轭物碱液经水解酸中和后采用高效液相色谱法测定,色谱柱为KromasilC18,流动相为水相(0·15%三乙胺和0·15%冰醋酸)-甲醇(95:5,V/V),检测波长为240nm。结果:5-氨基水杨酸检测浓度的线性范围为1～100μg·mL-1(r=0·9999);平均回收率为99·90%,日内及日间RSD≤2·25%;共轭物载药量为12·76%(n=3)。结论:本方法简单、快速、准确性高,可用于共轭物载药量的测定。