摘 要

口腔溃疡，一种难以根治的溃疡性损伤病症，常发生于缺乏角质化层或角化较差的口腔黏膜，如唇内侧、软腭、前庭沟、颊黏膜等。口腔溃疡发作时，患者口腔会感到剧烈疼痛，可能引发多种并发症，像口臭、恶心、慢性咽炎等。口腔溃疡严重时会对患者日常行为产生严重影响。现有口腔溃疡药物存在口感差、不良反应强、副作用大、复发率比较高等问题，很难达到令人满意的治疗效果。

口溃清含片为非处方药物，主要原料为山银花、青黛、冰片，可以有效治疗口腔溃病症，原料中山银花具有清热解毒、消炎止痛的作用。研究表明，青黛能通过诱导白细胞介素22的产生促进粘膜再生，进而治愈溃疡表面，较高浓度的冰片(0.5%)有抑菌作用。口溃清含片含服后有效成分迅速崩解，在溃疡部位产生较高浓度，病人服用后溃疡处疼痛感消失，周围组织不出现充血现象，溃疡面积缩小至完全愈合。相比其他口腔溃疡药物，口溃清含片具有处方简单、使用温和、安全高效，易于生产等优点，口溃清含片的成功研制并生产上市将是广大口腔溃疡患者的福音。

本人通过借鉴在校期间于武汉马应龙药业集团股份有限公司的生产车间实习经历，联系本科所学专业知识，参考了《制药工程》、《化工原理》、《制药反应工程》《药物制剂工程》《化工制图》等书籍文献，严格按照《GMP 实施指南》等设计规范和管理规范，在辅导老师和学长的指导下完成了具备合理有序的车间生产设计，生产过程紧凑有序、噪音小、能耗低、污染物排放严格符合 GMP 生产质量标准的“年产100万片口溃清含片车间工艺设计”。

本次毕业设计选择了合理的工艺路线，对相关数据完成了精准计算，合理安排设备选型，并完成了车间的布置设计。本毕业设计涵盖有：制备工艺选择、物料衡算、能量衡算、设备选型、“三废”处理 、定岗、定员等的相关描述及车间工艺流程图、车间平面布置图、主要设备装配图、主要管道分布图等五张图纸。

本次有关口溃清含片的车间工艺设计可满足中小型药企关于口溃清含片的生产需求，在设计过程中得到了很多老师和同学的帮助，充分运用了专业知识和实践经验。本设计的成功应用对指导口溃清含片的生产具有现实意义。

关键词：口溃清含片； 片剂； 车间工艺设计

Abstract

Oral ulcer, a kind of ulcerative sex injury disease that is difficult to cure radically, often happen in the mouth mucous membrane with poor keratinized layer or keratinized, wait like labial inside, soft palate, vestibular groove, buccal mucous membrane. When a mouth ulcer occurs, the patient's mouth can feel severe pain, which can lead to a variety of complications, such as bad breath, nausea, and chronic pharyngitis. Severe canker sores can have serious effects on patients' daily behaviors. The existing oral ulcer drugs have such problems as bad taste, strong adverse reactions, large side effects and high recurrence rate that it is difficult to achieve a satisfactory therapeutic effect.

Oral ulcer lozenges are non-prescription drugs, the main raw materials are lonicera hypoglauca, indigo, borneol, which can effectively treat oral ulceration. Lonicera hypoglauca in the raw materials has the functions of clearing heat and detoxification, anti-inflammatory and analgesic. Studies have shown that indigo can promote mucosal regeneration by inducing the production of interleukin-22, and then heal the ulcer surface. The higher concentration of borneol (0.5%) has a bacteriostatic effect. Oral ulcers lozenges contain active ingredients that disintegrate rapidly after taking, resulting in a relatively high concentration in the ulcer site. After taking the tablets, the pain in the ulcer site disappeared, no congestion was found in the surrounding tissues, and the ulcer area was reduced to complete healing. Compared with other oral ulcer drugs, oral ulcers lozenges have the advantages of simple prescription, mild use, safety and efficiency, and easy production. The successful development and production of oral ulcers lozenges will be a blessing to the majority of oral ulcer patients.

By drawing from the period of school of Wuhan MaYingLong pharmaceutical group company, production workshop internship, contact the undergraduate course and professional knowledge, reference for “Pharmaceutical Engineering”, “the Principles of Chemical Engineering”, “the Drug Reaction Engineering”, "Pharmaceutical Preparations Project", "Chemical Engineering Drawing" and so on books, in strict accordance with the GMP implementation guide " design specification and standard management, under the guidance of tutors and students, I complete a reasonable and orderly production workshop design. The production process is compact with low energy consumption, low noise and pollutant emission, which strictly conforms to the GMP production quality standard of "annual production of 1 million pieces of oral ulcers lozenges workshop process design".

This graduation project selected a reasonable process route, completed accurate calculation of relevant data, reasonable arrangement of equipment selection, and completed the layout design of the workshop. In order to reach the standard of GMP, we have also designed detailed measures and systems in production management, fire control and sanitation, personnel system, public system, "three wastes" treatment, environmental protection and other aspects. This graduation project covers: preparation process selection, material balance, energy balance, equipment selection, "three wastes" treatment, fixed post, fixed staff, etc. Maps include workshop process flow chart, workshop layout map, main equipment assembly map, main pipeline distribution map and other five drawings.

This workshop process design of oral ulcers lozenges can meet the production needs of small and medium-sized pharmaceutical enterprises. In the design process, many teachers and students have helped me. Besides, my professional knowledge and practical experience have been fully utilized. The successful application of this design is of practical significance to guide the production of Oral ulcers lozenges

Key words：Oral ulcer lozenges; lozenges; Workshop process desig

目 录

第一章 绪论 1

1.1 口溃清含片研究概况 1

1.2 处方及处方分析 1

1.2.1 法定处方 1

1.2.2 处方分析 1

1.2.3 制法 2

第二章 工艺流程设计 3

2.1 生产工艺流程图 3

2.2 生产工艺流程 4

2.2.1 领料称重 4

2.2.2 山银花与青黛的醇提 4

2.2.3 药物提取液的浓缩 4

2.2.4 制粒与整粒 4

2.2.5 总混 5

2.2.6 压片 5

2.2.7 铝塑包装 5

2.2.8 外包装 5

2.2.9 成品入库 6

2.2.10 质量控制点 6

第三章 物料衡算 7

3.1原辅料用量 7

3.1.1 任务 7

3.1.2 原辅料物料计算 7

3.1.3 原辅料实际投料量汇总 8

3.1.4 各工序收率指标 8

3.2 包装材料用量 9

3.2.1 包装办法 9

3.2.2 材料用量计算 9

3.3.3 包装材料用量汇总 9

第四章 能量衡算 11

4.1 能量衡算的依据 11

4.2 山银花醇提工艺热量衡算 11

4.3 青黛醇提工艺热量衡算 12

4.4 颗粒干燥过程的热量衡算 13