摘 要

复发性口腔炎(RecurrentAPhthousstomatitis，RAS)又称复发性口腔溃疡，简称口疮，是临床常见的口腔粘膜性炎症性病变，发病率居各种口腔粘膜病之首。目前国内临床关于本病的治疗药物和方法较多，中医多采用内服方药、漱口、局部涂擦、针灸等方法，据观察，上述方法存在临床效果不甚理想，治疗费用偏高，患者使用不便等问题。因此，研制疗效可靠、副作用小、奏效快，使用方便的新药制剂，具有很大的现实意义。口溃清含片是武汉药谷科技开发有限公司研制的中药第6类新药，是由金银花、青黛、冰片三味中药组成的口含片，具有清热解毒、消肿敛疮、止痛的功效，对复发性口疮有很好的疗效。

本论文对口溃清含片的提取工艺及成型工艺进行研究。通过正交实验对提取工艺进行优选，将药材分组按照正交表的条件进行提取，测定各组浸膏得率，并用所得浸膏制备供试品溶液，以高效液相色谱法测定其中绿原酸的含量，研究影响有效成分提取的工艺因素，选用流动相乙腈-0.4%磷酸溶液（12:88，V/V），以得膏率和样品中绿原酸的含量为指标，优选口溃清含片的提取工艺。结果显示，当溶剂用量为10倍，提取时间为1.5 h，乙醇浓度为为70%，提取次数为3次时，提取效益最佳。按最优工艺提取出浸膏之后进行辅料的筛选实验，最终选用淀粉:糖粉质量比为2:1，15%的淀粉浆为粘合剂，0.2%硬脂酸镁为润滑剂。本论文通过系统的实验对口溃清含片的提取工艺及成型工艺进行了初步研究，为口溃清含片的成功研制打下了一定基础。

关键词：口溃清含片；提取工艺；绿原酸；正交实验；辅料

Abstract

Recurrent dysplastic disease (RecurrentAPhthousstomatitis, RAS), also known as recurrent oral ulcers, referred to as mouth sores, is a common clinical oral mucosal inflammatory disease, the incidence of various oral mucosal disease first. At present, the clinical treatment of the disease and methods are more traditional Chinese medicine and more use of oral prescription, mouthwash, local rub, acupuncture and other methods, it is observed that the above method is not ideal clinical effect, high cost of treatment, patients use Inconvenience and other issues. Therefore, the development of reliable, side effects, quick, easy to use new drug preparation, has great practical significance. It is made of honeysuckle, indigo and borneol herbal medicine. It has the effect of clearing away heat, detoxifying and swollen soreness and relieving pain. It is a kind of medicine which is developed by Wuhan Yao Gu Technology Development Co., Recurrent aphthous have a good effect.

  In this paper, the extraction process and molding process of the solution were studied. The extraction process was optimized by orthogonal experiment. The extraction of the medicinal materials was carried out according to the conditions of the orthogonal table. The yield of each group was determined and the test solution was prepared by the obtained extract. The solution was determined by high performance liquid chromatography Acid content to study the factors that affect the extraction process of active ingredients, the choice of liquidity for the acetonitrile -0.4% phosphoric acid solution (12:88，V/V), and ultimately to the paste rate and the content of chlorogenic acid in the sample as an indicator. The results showed that the extraction efficiency was the best when the amount of solvent was 10 times, the extraction time was 1.5 h, the ethanol concentration was 70% and the extraction time was 3 times. According to the optimal process to extract the extract after the excipient screening experiment, the final choice of starch and sugar powder ratio of 2: 1, 15% of the starch pulp as a binder, 0.2% of the magnesium stearate as a lubricant.In this paper, through the systematic experiment, the extraction process and the forming process of the chip were studied, which laid a foundation for the successful development of the mouth tablets.

Key words: Koukuiqing Mouth tablets method；Extraction process；Chlorogenic acid；orthogonal design of experiment；Accessories

目录

第一章 绪论 1

1.1 中药提取工艺的发展概况 1

1.1.1 煎煮法 2

1.1.2 浸渍法 2

1.1.3 渗漉法 2

1.1.4 回流提取法 3

1.1.5 微波萃取技术 3

1.1.6 超临界流体提取法 3

1.2 高效液相色谱法的介绍 3

1.3 口溃清含片研究现状简介 4

1.3.1 金银花 4

1.3.2 青黛 5

1.3.3 冰片 5

第二章 正交实验优化口溃清含片的提取工艺 6

2.1 实验仪器与实验药品 6

2.1.1 实验仪器 6

2.1.2 实验药品 6

2.2 方法与结果 6

2.2.1 提取条件与测定条件的选择 6

2.2.2 药材鉴别 6

2.2.2.1 金银花的鉴别 7

2.2.2.2 青黛的鉴别 7

2.2.2.3 冰片的鉴别 7

2.2.3 正交实验设计 8

2.2.4 样品的制备 8

2.2.4.1 药材的前处理 8

2.2.4.2 制备实验过程 8

2.2.5 绿原酸含量测定 9

2.2.5.1 供试品溶液的制备 9

2.2.5.2 对照品溶液的制备 9

2.2.5.3 色谱条件 9

2.2.5.4 线性关系的考察 9

2.2.5.5 精密度试验 10

2.2.5.6 稳定性试验 10

2.2.5.7 重复性试验 10

2.2.6 正交试验结果及方差分析 11

2.2.7 优选工艺的验证 11

第三章 口溃清含片成型工艺研究 13

3.1 填充剂的选择 13

3.2 粘合剂的选择 13

3.3 润滑剂的选择 14

3.3.1润滑剂的种类筛选 14

3.3.2确定润滑剂的用量 14

3.4 制备方法验证 14

第四章 结论 16

参考文献 17

致谢 19

1. 绪论

复发性口腔溃疡又称复发性口疮，简称口疮，是临床上常见的口腔疾病，其发病率居各种口腔粘膜病之首，在中医里属于口疮、口靡范畴。临床以局部口腔粘膜溃疡、疼痛、反复发作，久治不愈等为特点。但其发病原因尚不清楚，一般认为与病毒感染、过敏反应、内分泌紊乱、免疫力低下等因素有关，精神紧张、食物、药物、维生素或微量元素缺乏等都可能诱发口腔溃疡。现代医学对口疮反复发作者的疗效不是十分满意。

西医在临床上用于治疗复发性口腔溃疡的药物有四环华素片、醋酸地塞米松粘贴片、复方千金藤软膏、西咪替丁等，但无法根治。而中医辨证论治能取得较好的疗效。中医认为口疮的发生，外因以热毒为主，内因多为情志内伤，饮食不节，房室劳倦所致。诚如《诸病源候论·唇口病诸候·口舌疮候》所言：“手少阴心之经也，心气通于舌；足太阴脾之经也，脾气通于口。脏腑热盛，热乘心脾，气冲于口与舌，故令口舌生疮也”。其上炎之火多为虚火，《医贯》云:“口疮，上焦实热，中焦虚寒，下焦阴火，各经传变所致。”本病病机应属正虚邪恋，寒热错杂[^[1]]，治疗时应注意标本兼顾，攻补双管齐下，以消除病因、增强体质、对症治疗为主，治疗方法应坚持全身治疗和局部治疗相结合，中西医治疗相结合，生理和心理治疗相结合。但在中医治疗时需煎熬中药，过程麻烦，且疗程较长，口感苦涩，患者多有抵触。因此采用现代制药技术将临床上行之有效的传统方药进行科学加工，制成方便服用和携带且安全有效的制剂有着重要意义。目前，市场上治疗口腔溃疡病及咽炎的中药制剂有西瓜霜含片、华素片、草珊瑚含片等，但是对复发性口腔溃疡疗效并不满意。