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 详细处方信息以本药内容附件PDF文件（201033118573627.pdf）的“原文Priscribing Information”为准
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部分中文mesalamine 处方资料（仅供参考）

一、项目概述
   1、项目名称：美沙拉嗪肠溶缓释微丸胶囊
   2、申报类别：化药5类
   3、适应症：溃疡性结肠炎的维持性治疗
   4、规格：0.375g/粒
   5、产品优势：微丸技术、缓控释制剂技术，24小时缓释制剂。
二、溃疡性结肠炎的治疗现状和存在的问题
    溃疡性结肠炎（ulcerative colitis，UC）是一种发生于结肠粘膜的慢性、炎症性及溃疡性疾病，最典型的特征是血性腹泻。近年我国UC发病呈加快趋势，最近10年报道的病例数目是过去10年的3.8倍，而患者构成以慢性反复发作型为主。在缓解期如不进行干预，UC患者1年内的复发率则可能高达70％。由于UC病变范围广泛、病情反复发作、治疗效果欠佳，病情迁延不愈，癌变可能性大等特点，该病已被世界卫生组织确定为现代难治疾病。
    UC的治疗方法包括药物治疗、营养治疗、心理治疗及手术治疗，其中药物治疗是治疗溃疡性结肠炎的主要方法。而美沙拉嗪（又名：5-氨基水杨酸，5-ASA）及其衍生物被证明是目前临床最常用的、有效的药物。
    美沙拉嗪治疗溃疡性结肠炎的作用机制尚不甚明了，可能为局部作用而非系统作用。美沙拉嗪可在患者肠道内与大肠粘膜直接接触发挥作用，抑制肠粘膜中前列腺素E2、白三烯、及5-羟基十二碳四烯酸的合成和释放。
    美沙拉嗪有局部用药和口服制剂，其中局部用药剂型有栓剂和灌肠液，对于轻-中型的远端结肠炎的患者，栓剂、灌肠剂的给药深度受限，无法治疗广泛性结肠炎。美沙拉嗪若直接口服可被胃和十二指肠迅速吸收，这样不能有足够量药物到达结肠而起抗炎作用，同时吸入体内的药物易产生肾毒性，因此口服制剂需要做成肠溶制剂，但无论是国产还是申请进口的美沙拉嗪肠溶制剂，维持期治疗都是一天3-4次，对于患者长期用药来说，存在诸多不便。因此做成肠溶+缓释制剂，显得很有意义！
三、美沙拉嗪肠溶缓释微丸胶囊的特点与优势
    1. 采用肠溶+缓释技术，使药物在炎症局部有较好的生物利用度，避免上消化道吸收，减少药物的全身性作用。美沙拉嗪肠溶缓释微丸胶囊，在胃内胶囊溶解破裂，释放出微丸，但此时美沙拉嗪并不被释放和吸收，到达小肠后，在肠液pH≥6 时，微丸包衣溶解开始释放药物，微丸内为缓释骨架结构，药物缓慢释放，有利于在炎症局部维持较长时间。先前已上市的其他肠溶片在pH≥7时才开始释放药物，而已发布的研究数据证明，部分UC患者的小肠和大肠液pH值从未达到7。因此，该美沙拉嗪肠溶缓释微丸胶囊为新型的、先进的药物给药系统，该给药系统可实现在小肠部位即开始释放药物，持续到整个结肠，治疗效果更佳。
    2.  每天用药1次：药物微丸是缓释骨架结构，可在炎症局部缓慢释放药物，维持长时间的局部药物浓度，每天早晨1次服药即可。
四、国内外研制及上市情况
    目前国内国产美沙拉嗪肠溶制剂有2家生产，但用于UC维持期治疗均需每日给药3次；进口上市品种有法国爱的发公司（颗粒剂，商品名艾迪莎）、德国霍克大药厂（肠溶片、灌肠剂、栓剂，商品名沙尔福）、丹麦辉凌制药（缓释片、栓剂，商品名彼得斯安）。
国家药监局新药评审中心数据库查询，瑞士Tillotts药厂2006年申报美沙拉嗪缓释片，商品名为Asacol，虽然名称翻译为缓释片，但其治疗维持期UC 患者仍需每日1.6g，分次服用，并非真正意义上的缓释制剂（extended-release）。
    2008年10月31日,美国FDA批准了Salix Pharmaceuticals, Ltd.公司的美沙拉嗪缓释胶囊（mesalamine extended-release capsules），商品名为Apriso ，该制剂为目前唯一的每日给药1次的24小时缓释制剂。我们开发的美沙拉嗪肠溶缓释微丸胶囊即仿制Apriso设计思路，有利于国内sfda的审评审批。

About APRISO
Salix Pharmaceuticals introduces APRISO™ (mesalamine) 0.375 g for the treatment of ulcerative colitis (UC). APRISO is the first and only once–daily 5–ASA featuring Intellicor™ delayed and extended delivery–for the successful long–term* management of UC.

APRISO begins releasing mesalamine at a pH ≥ 6 and gradually distribute mesalamine throughout the entire colon. APRISO has been shown to be effective in helping UC patients stay in remission for up to six months.

For use in patients 18 years of age or older. Apriso can be taken with or without meals.

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Bringing the benefits of APRISO to UC patients.
APRISO is a type of medication called a 5–aminosalicylic acid or 5–ASA. 5–ASAs are anti-inflammatory medications that reduce irritation of the colon. APRISO is the first and only once-daily 5–ASA featuring INTELLICOR™ delayed– and extended–release delivery — for the successful long-term (6 months) management of ulcerative colitis (UC).

Studies show APRISO provides extended relief from key ulcerative colitis (UC) symptoms for up to six months, including:Rectal bleeding；Diarrhea；Flare-ups。

Benefits include:Protection. APRISO works throughout the entire colon.Simplicity. APRISO is taken once a day.Convenience. APRISO may be taken with or without meals.Targeting. The delayed– and extended–release delivery releases mesalamine at a pH≥6, gradually distributing it throughout the entire colon.

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Indications for APRISO：Maintenance of remission of ulcerative colitis (UC) in adults.

Adult dose for APRISO：≥18yrs: 1.5g once daily in the AM.

Children's dosing for APRISO：<18yrs: not recommended.

Precautions for APRISO：Sulfasalazine allergy. Renal dysfunction or history of renal disease; assess renal function at the beginning and periodically during treatment. Hepatic impairment. Elderly (monitor CBCs). Pregnancy (Cat.B). Nursing mothers.

Interactions for APRISO：Do not co-administer with antacids.

Adverse Reactions for APRISO：Headache, GI upset, upper abdominal pain, nasopharyngitis, flu-like symptoms, sinusitis; renal impairment, mesalamine-induced acute intolerance syndrome (eg, cramping, abdominal pain, bloody diarrhea, fever, headache, rash); discontinue if occurs.

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APRISO is a locally acting aminosalicylate indicated for the maintenance of remission of ulcerative colitis in patients 18 years and older. APRISO is contraindicated in patients with hypersensitivity to salicylates or aminosalicylates (sulfasalazine) or to any of the components of APRISO capsules. It is recommended that patients have an evaluation of renal function prior to initiation of APRISO therapy and periodically while on therapy. Exercise caution when using APRISO in patients with known renal dysfunction or a history of renal disease. There have been reports of hepatic failure in patients with pre–existing liver disease who have been administered mesalamine. Caution should be exercised when administering APRISO to patients with liver disease. The recommended dose of APRISO is four 0.375–g capsules once daily in the morning (1.5 g/day) with or without food. Because dissolution of the coating of APRISO granules depends on pH, APRISO should not be coadministered with antacids. Patients with phenylketonuria should be aware that APRISO contains aspartame, equivalent to 2.24 mg of phenylalanine per day. In 2 well–controlled clinical trials, the most common treatment–related adverse events occurring in at least 3% of adult patients taking 1.5 g/day of APRISO were headache (11% vs 8% for placebo), diarrhea (8% vs 7% for placebo), upper abdominal pain (5% vs 3% for placebo), nausea (4% vs 3% for placebo), nasopharyngitis (4% vs 3% for placebo), influenza and influenza–like illness (4% vs 4% for placebo), and sinusitis (3% vs 3% for placebo).

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 详细处方信息以本药内容附件PDF文件（201033118573627.pdf）的“原文Priscribing Information”为准
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