5-氨基水杨酸口服制剂及联合中药在炎症性肠病治疗中的应用

Application of 5-Aminosalicylic Acid Oral Formulations and Its Combination with Traditional Chinese Medicine in Treatment of Inflammatory Bowel Disease

5-氨基水杨酸(5-ASA)是1种从中药柳树皮中分离提纯得到的天然抗炎活性成分水杨酸的衍生物,别名阿米诺水杨酸、美沙拉嗪,是临床治疗炎症性肠病(IBD)并预防其复发的一线药物。尽管目前莎尔福(Salofalk)、亚沙可(Asacol)和潘他沙(Pentasa)等5-ASA口服结肠靶向制剂已广泛用于IBD的临床治疗,但仍存在在小肠提前释药和受胃肠道生理状态影响显著等制剂缺陷、对克罗恩病和重度溃疡性结肠炎(UC)治疗效果不佳等临床未满足的需求,以及减少UC患者黏膜菌群多样性、长期使用增加用药风险和降低患者服药依从性等问题。开发硅胶纳米粒、水凝胶等新型递药载体,基于pH依赖、时滞控制和菌群/酶触发等多机制结合释药原理设计新型口服结肠靶向制剂从而解决制剂缺陷问题,提高5-ASA疗效和患者服药耐受性、依从性是目前制剂研究的重点。此外,5-ASA口服制剂联合中药保留灌肠、中药口服制剂和注射液等治疗IBD可发挥协同抗炎作用,实现增效减毒目的。对5-ASA口服制剂品种、近年来新型制剂和递药载体的研究进展,以及与中药联用的临床应用和研究现状等进行综述,为5-ASA口服制剂的剂型改造、载体材料研究和临床用药等提供参考。

The derivative 5-aminosalicylic acid(5-ASA),also known as amino salicylic acid or mesalazine,is derived from natural anti-inflammatory compound salicylic acid isolated and purified from willow,and is a first-line drug for the treatment and prevention of inflammatory bowel disease(IBD)relapses.Despite the widespread clinical use of oral colon-specific 5-ASA formulations such as Salofalk,Asacol,and Pentasa in the treatment of IBD,several unmet clinical needs and formulation deficiencies persist,including premature drug release in the small intestine,significant influence by gastrointestinal physiological conditions,suboptimal efficacy in treating Crohn's disease(CD)and severe ulcerative colitis(UC),reduced mucosal microbiota diversity in UC patients,increased risk with long-term use,and decreased patient compliance.To address these issues,current research focuses on developing novel drug delivery carriers,such as silica nanoparticles and hydrogels.These carriers are designed based on multi-mechanism drug release principles,including pH-dependence,time-delay control,and microbiota/enzyme-triggered release to improve the efficacy of 5-ASA and to enhance patient tolerance and adherence to treatment.Furthermore,combining oral 5-ASA formulations with traditional Chinese medicine(TCM)therapies,such as retention enemas,oral decoctions,and injections,can synergistically enhance anti-inflammatory effects,achieving the goal of increased efficacy and reduced toxicity.This review covers the progress in the development of various oral 5-ASA formulations,recent advancements in new formulations and drug delivery carriers,and the current status of clinical applications and research on combining 5-ASA with TCM.This study is expected to provide references for the modification of 5-ASA dosage forms,research on carrier materials,and clinical use,ultimately improving treatment outcomes for IBD patients.