论文总字数：17188字

摘 要

功能性消化不良(FD)，又被人称为胃动力不足或胃动力障碍，是由非器质性病变引起的一组消化不良症候群,表现为持续性或反复发作性餐后饱胀、腹部胀气、早饱、嗳气、厌食、恶心、呕吐、嘈杂、胸骨后痛、反胃等症状,且经胃镜等多种检查无特殊异常。据统计,FD发病率高,约占消化病专科门诊患者的50%[1]。而FD的治疗无异常,疗效的个体差异大,可以联合用药。西医一般采用促胃动力药,抑制胃酸,保护胃黏膜,抗抑郁剂及心理治疗等措施对症治疗;促胃动力药和抑制胃酸分泌仍是目前治疗的主要药物,同时也采用精神治疗、心理治疗、生活方式治疗、饮食习惯调整等辅助治疗。因社会的发展，生活节奏日趋紧张，功能性消化不良的发病率还有逐年升高的趋势，此类疾病的药物市场也将稳步增长，因此研制一种安全有效的治疗功能性消化不良的药具有重要意义。

枸橼酸莫沙必利为大日本制药株式会社开发的胃动力药，于1998年12月首次在日本上市。本品剂型有2．5mg、5mg片剂和1 96散剂，国外商品G~smotin [2]，临床用于慢性胃炎、功能性消化不良、反流性食管炎及手术伴随的一系列胃肠道症状的缓解。本晶为新型胃动力药，强效、选择性5．HT4受体激动剂。莫沙比利的化学结构与西沙必利相似，两者同为苯酰胺衍生物。这两种药物的胃动力作用机制也有相似之处，均通过激动肠肌层神经丛的5．HT4受体，使神经末梢的乙酰胆碱释放增加，从而促进胃排空[3]。与西沙必利不同的是，本品选择性作用于上消化道，对结肠运动无影响，可减少因结肠运动亢进导致的腹痛、排便次数增加、腹榻和软便等副作用，且由于其与多巴胺D2 受体无亲和力，可避免因拮抗多巴胺D2 受体导致的锥体外系反应及催乳素分泌增多等副作用。另外，电生理研究表明，本品无延长离体心室肌和蒲氏纤维动作电位时程的作用，故具有更好的安全性。

通过实验了解枸橼酸莫沙必利的理化性质，根据不同剂型的需要和制备工艺的不同流程，运用高效液相色谱法对药物在不同条件下的稳定性、溶解度进行考察，运用加速试验法考察主药与辅料的相容性，为处方设计时辅料的筛选研究提供依据[4]。

关键词：功能性消化不良 枸橼酸莫沙必利 处方前研究

Abstract

Functional dyspepsia (FD), also known as the lack of gastric motility and gastric motility disorder, is caused by nonorganic lesions in a group of indigestion syndrome, manifested as persistent or recurrent postprandial fullness, abdominal bloating, early satiety, belching, nausea, vomiting, anorexia, noisy, retrosternal pain, nausea and other symptoms, and endoscopic examination without exception etc.. According to statistics, the incidence of FD is high, about 50% patients with digestive disease clinic. While FD treatment without exception, individual differences in efficacy of combination therapy, can. Western medicine generally use the prokinetic drug, the inhibition of gastric acid, protection of gastric mucosa, antidepressants and psychological treatment, symptomatic treatment measures; the main drug prokinetic drugs and inhibition of gastric acid secretion is the current treatment, but also the spiritual therapy, psychotherapy, lifestyle, diet adjustment, treatment of adjuvant therapy. Because of the development of society, the pace of life is becoming increasingly tense, the incidence rate of functional dyspepsia and the increasing trend year after year, this disease drug market will grow steadily, so it is very important to the development of a safe and effective treatment of functional gastrointestinal adverse drug.

Mosapride citrate is the stomach power medicine Dainippon Pharmaceutical Co. Ltd. to develop, market for the first time in 1998 December in japan. The product forms are 2.5mg, 5mg tablets and 196 powder, imported products G~smotin, clinical used to relieve chronic gastritis, dyspepsia, reflux esophagitis and operation with a series of gastrointestinal symptoms. This work is a new type of gastric motility, potent, selective 5.HT4 receptor agonist. The chemical structure and cisapride Mosa Billy similar, both are the same as benzamide derivatives. These two kinds of mechanisms of drug action of gastric motility is similar, both through the activation of intestinal myenteric plexus of the 5.HT4 receptor, the nerve endings of the increased release of acetylcholine, thus promoting gastric emptying. And cisapride is different, the selective effect on upper digestive tract, no effect on colonic motility, and can reduce the frequency of abdominal pain, bowel caused by colon motility increased, abdominal couch and soft stool and other side effects, and because of its D2 dopamine receptor with no affinity, can avoid the extrapyramidal reactions and prolactin causes because of blockade of dopamine D2 receptor secretion and other side effects. In addition, electrophysiological studies show that, the goods without extending the isolated ventricular muscle and Purkinje fibre action potential duration effect, safety is better.

To understand the physical and chemical properties of mosapride citrate through experiments, according to different process needs and preparation of different dosage forms, using high performance liquid chromatography was studied on the stability of the drug in different conditions, the solubility, the compatibility of the main medicine and supplementary accelerated test method, provide the basis for the selection of prescription the design of accessories.

Keywords: functional dyspepsia Mosapride citrate Preformulation study

目录

摘 要 I

Abstract II

第一章 文献综述 1

1.1枸橼酸莫沙必利 1

1.1.1枸橼酸莫沙必利的性状 2

1.1.2枸橼酸莫沙必利的鉴别 2

1.1.3枸橼酸莫沙必利的检查 2

1.1.4枸橼酸莫沙必利的含量测定 2

1.2 思考设计实验................................................................................................................ 2

第二章 枸橼酸莫沙必利处方前研究 4

2.1试验部分 4

2.1.1 试验材料 4

2.1.2 试验仪器 4

2.1.3 枸橼酸莫沙必利在不同溶剂中的紫外吸收 5

2.1.4 枸橼酸莫沙必利原料药的稳定性 5

2.1.5 有关物质检查......................................................................................6

2.1.6 枸橼酸莫沙必利在不同pH下的稳定性..............................................7

2.1.7 枸橼酸莫沙必利在不同pH中的溶解度.................................................7

2.1.8原辅料相容性试验.....................................................................................8

第三章 试验的结果与讨论 9

3.1检测波长的确定 9

3.2原料药的稳定性 9

3.3有关物质检查 10

3.4原料药在不同pH下的稳定性........................................................................11

3.5溶解度..............................................................................................................11

3.6 原辅料相容性试验.........................................................................................12

第四章 总结与展望 13

4.1 总结 13

4.2 展望 13

参考文献 14

致 谢 15

第一章 文献综述

1.1枸橼酸莫沙必利

1.1.1枸橼酸莫沙必利的性状

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