【作者】 陆原；

【导师】 禤国维；

【作者基本信息】 广州中医药大学 ， 中西医结合临床， 2002， 博士

【摘要】 非淋菌性尿道炎(Nongonococcal Urethritis，NGU)是由淋病奈瑟氏菌以外的其它病原体引起的尿道炎，是一种性传播疾病(Sexually transmitted diseases，STDs)，可伴有其它多种合并症。本研究旨在通过一系列相关临床、实验研究，初步探讨系列制剂——中药尿路清合剂及妇阴康洁栓剂对CT感染NGU(又被称作CGl)的作用机理，从多方面，多角度为中医药治疗本病提供理论依据。 非淋菌性尿道炎(NGU)是目前性传播疾病中最常见的一种，国外报道其发病率不断增高，有的西方国家已高居性病第一位。目前，随着性观念的改变，对外交流的加强，人员流动性增加以及检验水平的不断提高，NGU的检出率在我国也出呈现出明显的上升趋势。NGU主要由与带有病原菌者性接触而传染。其病原体可有上述的沙眼衣原体(23％--55％)，解脲支原体(20％--40％)，还可有滴虫(2％--5％)、白念珠菌、包皮杆菌以及罕见的HSV、兰氏鞭毛虫等。其中随着研究的深入和检测水平的不断提高，对沙眼衣原体的认识取得了很大进展。 中医认为CT感染的NGU属于中医淋症、白浊范畴，发病主要与房事不洁，外感湿热毒邪，侵犯下焦，膀胱气化失司，水道不利有关；病程日久则与久淋体虚，劳伤过度，以致脾肾亏虚，膀胱气化无权，湿邪久恋有关。中西医对本病均有较多治疗方法，但其中西药的疗效虽高，也存在耐药菌株增加，复发率高，药物副作用大等问题。 本文在复习了中、西医对NGU认识的基础上，结合导师——广东省名中医禤国维教授诊治该病的临床经验，研制纯中药制剂尿路清合剂，并且制成了阴道栓剂——妇阴康洁，通过实验研究初步探索其抗CT作用和其他一些相关的作用机制，为其进一步研究、应用提供一定的科学依据。 从治疗的角度讲，过去人们对Ct的抗药研究甚少，一直认为Ct对抗生素敏感，把造成Ct感染迁延、持续的主要原因归结为其发病过程隐匿，不易被发现所致，一旦确诊，Ct对抗生素治疗的反应良好，即可及时清除；然而，在临床实践中Ct的清除率并不令人满意，有些经长期Ct的治疗随诊发现即使是在多次系统的抗Ct治疗后，仍有很高的阳性检出率，部分Ct顽固难治已经是客观事实，对于迁延难愈者，目前尚无明确有效的治疗方案。在治疗方案的选择上，国内外的研究认为，衣原体泌尿生殖道感染的治疗仍以抗生素为主，其中又以四环素类药物为首选，红霉素和阿奇霉素可作为选择用药，某些喹诺酮类药物也具有较好的抗沙眼衣原体作用，对于NGU初发的病人，国内外存在一些不同的具体治疗方案。而对于复发性或持续性NGU病例尚无有效的治疗方案，只是存在一些推荐方案。 非淋菌性尿道炎为临床常见病，多发病，临床危害性较大。很多学者对此也进行了较广泛而深入的研究，但就总体而言，这些研究均缺乏实验研究和临床研究的系统性结合，而且目前临床应用专治此病的中药栓剂未见有报道，因此我们根据临床经验和传统的中医药理论，发挥中医优势，并结合现代医药学技术，按照新的中药制剂研制要求，研制具有清热解毒、燥湿止痒之功效的中药复力治疗女性泌尿生殖系CT感染，并在口服汤剂、合剂己经取得良好疗效的基础上，改变剂型，开发治疗女性泌尿生殖系CT感染的新剂型—一、妇阴康洁。栓剂，必将对STD防治和社会公共健康产生深远的社会意义。 中药栓剂在发挥局部治疗作用可显示出作用迅速、能有效控制症状等诸多优点，栓剂在给药时，药物从栓剂中释放后，可以直接进入粘膜，抑制衣原体的生长、繁殖。因此运用传统中医理论，结合现代先进中药制剂技术制备易被患者接受，疗效肯定，副作用少，复发率低，有针对性，使用方便的治疗女性泌尿生殖系CT感染的中药制剂—一、妇阴康洁。栓剂，将产生良好的社会效益和经济效益。 尿路清以甘淡利尿，清热解毒的白花蛇舌草为君，全方由多个药对组成，共奏清热解毒、补肾通淋，健脾化浊之功，且具备攻补兼施，阴阳双补等配伍特点。现代药理研究也充分证实了组方中的各单味药具有显著的抑菌，提高机体免疫功能等作用。而妇阴康洁栓则有清热解毒、燥湿止痒的作用，在临床上应用有良好的疗效。 针对女性下生殖道的某些病变，治疗多有内服、外用两种给药方式，但根据其发病特点，医学界认为外用制剂有其不可替代的优越性。目前常用的妇科外用制剂有洗剂、糊剂、散剂、栓剂等，但使用起来也有诸多不便，如有的因选择基质不当使药物在体温状态下熔化而造成流失和污染衣物；有的使用不便，有的则停留时间短，难以充分发挥药效。女性CGI在成为严重危害妇女身心健康疾病的同时，也亟须医学工作者开发研制出针对性强，使用方便、高效、无刺激，能自洁内环境，不污染衣物的新的外用制剂。通过检索，我们发现：在中药提取后制成栓剂，并开展其治疗女性泌尿生殖系沙眼衣原体感染的实验研究与临床研究，使之系统性结合的研究工作，亦未见报道。针对此空白，我们主要对药材进行提取、浓缩后和基质混合制备栓剂，然后进行稳定性试验，制订出栓剂的质量标准，进行质量检查，并进行和释放度研究和药效学研究（包括抗炎试验、抑菌试?更多还原

【Abstract】 The main experimental parts of this dissertation were carried out in The second affliated hospital of Guangzhou University of TCM, the school of Chinese Materia Medica, Guangzhou University of TCM, and Foshan medical school during the years 1999-2002.I wish to express my deepest gratitude to my supervisor Professor Guo-wei XUAN, for his continuous interest most valuable help, support,comments and tireless encouragement throughout this work.Special thanks are due to Da-Can CFIEN, for his constructive discussion and advice, pleasant cooperation, and for his most valuable help, which made life easier.I would like to express my sincerest gratitude to Professor Zhaoshen HUANG, the head of the school of Chinese Materia Medica, Guangzhou University of TCM . I would like to express my sincerest gratitude to the teachers of The affiliated hospital of Foshan medical school, for their providing excellent research facilities.I am especially grateful to Bao-jian Fan, Ji-wen Zhao, Ning wang from Department of epidemiology, Medical college of DongNan University, for their most valuable help in a variety of aspects, and for their supports, comments and enjoyable cooperation throughout this work.I also owe my thanks to Anping Yang, for his most valuable helps, fruitful discussion and cooperation, and for his introducing me to the field of Chinese material medica.Sincere thanks are due to all the personnel staff and colleagues at Dermatology Department of Guangdong provincial T.C.M hospital, for creating a friendly and helpful working atmosphere. I also wish to extend my warm thanks to all the people at Guangdong provincial T.CM. hospital ,who have helped me in various aspects.I would like to express my deepest thanks to my parents and my brother, my sister for their everlasting love, understanding, support and encouragement they have given me in my life.Clinical And Experimental Studies On Niaoluqing And FuyinkangjieTreatingNongonococcalUrethritis(cervicitis) Caused By CT ABSTRACTPart I General IntroductionNongonococcal urethritis(NGU) is a kind of venereal disease, which is caused by C. Trachomatis(CT),U. Urealyticum(Uu),M. Hominis (Mh), herpes simplex virus II( Hsv2) Candida(Cd), T. Vaginalis (Tv) and other agents. Among them,CT is knownas an important pathogenic factor, and was transmitted through sexual intercourse. Men complain of dysuria and mucoid or mucopurulent urethral discharge, vaginal discharge is perhaps the most common complaint of women. NGU caused by CT has a double importance:first, as a disease which affects the patient locally and generally, by causing fertil and steril ,it may ascend to endometrium and fallopian tubes, by causing salpingitis and other complications; secondly; by causing neonatal pneumonia, or by affecting the child with neonatal infection.Up to 50%of cases of nonspecific urethritis are caused by Chlamydia trachomatis. Chlamydiae are bacterica which require living cell (cell culture) for cultivation. They can be the primary cause of a chronic urethritis or be a concomitant infection in other types of urethritis (especially gonorrhea). Since Halberstadter and von Prowazek, this urethritis has been described as inclusion blennorrhea because inclusion bodies are detectable microscopically in epithelial cells affected by the pathogen on staining with Giemsa. The incubation time may be 4 days to 1 month, and the inflammation is usually limited to the anterior urethra.The chlamydiae can be detected in urethral smears using monoclonal antibodies and fluorescence microscopy. Kits for routine investigations are available Definite proof of Chlamydia trachomatis is based on culture of the organisms on McCoys cells in specialized laboratories and identification using iodine or Giemsa stain or fluorescence-labeled monoclonal antibodies.Tetracycline HCL SOOmg orally 4 times daily, doxycycline lOOmg orally twice daily, or erythromycin SOOmg 4 times daily; all for days.NGU is a part of stranguria with turbid urine (a syndrome marked by dif更多还原