摘要
米非司酮配伍米索前列醇是目前终止早期妊娠的较广泛的药物流产方法，完全流产率可达90％以上，但药流过程中均伴有一定的副作用。催经止孕颗粒原剂型为合剂，经临床预试，配合米非司酮有确切的抗早孕作用，可替代或部分替代药流中的米索前列醇，且可显著减轻药流的副作用。本课题运用现代制剂技术，对催经止孕颗粒的制备工艺及质量标准进行了研究。
催经止孕颗粒由益母草、川芎、当归、枳壳、莪术、红花、水蛭七味药组成，益母草为方中君药，本研究采用雷氏铵盐剩余比色法测定益母草中总生物碱含量，以总生物碱含量和浸出物含量为指标，正交试验优选益母草、红花提取工艺，优化提取工艺为：12倍量80％乙醇提取1.5h，提取3次。
通过对挥发油的提取及β-环糊精包合工艺研究，优化包合工艺为：油与β-环糊精的比例为1∶8(ml∶g)，包合温度为40℃，包合时间为2h，加水量为β-环糊精用量的10倍。包合后采用显微镜法、差示量热分析、TLC分析，结果表明，挥发油包合物已形成，包合前后成分一致，此法简便可行，提高了挥发油部位的稳定性，掩盖了其不良气味，使挥发油液体变成固体粉末，便于制成固体制剂。
超微粉碎是近年来国际上发展非常迅速的一项新技术，本研究采用超微粉碎新技术制备水蛭超微粉，研究比较了水蛭普通粉、水蛭超微粉对大鼠离体子宫的作用，结果表明，同等剂量的水蛭微粉对离体子宫的兴奋作用明显优于普通粉，体现了超微粉碎新技术的发展优势和应用前景。
对催经止孕颗粒的质量标准进行了研究，采用TLC鉴别方中的益母草、当归、川芎、枳壳；HPLC法测定了方中当归、川芎中的阿魏酸含量，所建方法简便、准确，重现性好，可作为催经止孕颗粒的质量标准，为新药开发研究奠定了基础。
The compatibility of Misoprosol and Mifepristone is a widely used method of medical induced abortion at present, which complete abortion rate is beyond 90 percent, but the side effect of medicine occurs simultaneously. The original form of Cuijingzhiyun granules is decoction. The clinic experiments have indicated that the compatibility of Cuijingzhiyun granules and Mifepristone has certain effect for termination of early pregnancy and alleviate the side effect of medicine. With the new preparation technology, the thesis has studied the preparation processes and quality standard of granules.
Cuijingzhiyun granules consist of Herba Leonuri (Yimucao) , Rhizoma Chuanxiong(Chuanxiong), Radix Angelicae Sinensis(Danggui), Fructus Aurantii(Zhike), Rhizoma Curcumae(Ezhu), Flos Carthami(Honghua) and Hirudo(Shuizhi). The main medicine is Herba Leonuri (Yimucao), the determination of stachydrine hydrochloride in Herba Leonuri was determined by ammonium reineckate spectrophotometry method. Using total alkaloid content and extracts as markers, the optimum extraction technology of Herbal Leonuri and Flos Carthami was selected with the orthogonal experiment. The optimum extraction technology is as follows: adding 12 times 80% ethanof, reflux-extraction 3 times, 90min for each time.
By studying volatile oil extraction and the technology process of inclusion compound, the optimum preparation condition of inclusion compound of B-cyclodextrin with volatile oil was that: the ratio of volatile oil to B-CD was
l:8(ml:g),adding 10 times water, stirring 2h at 40C. The inclusion compound formation was proved by microscopical image-forming, DSC and TLC. It was indicated that the character of volatile oil before and after being included was uniform. The methods were accurate and quick, the stability of volatile oil can be obviously raised and the punget smell of volatile oil was covered by the inclusion compound, the state of volatile oil changed to solid from liquid, which was convenient to preparation.
Ultramicro pulverization is a new technology that develops very rapidly in recent years.Ultramicro powder of Hirudo was prepared with new methods of ultramicro pulverization. In the experiment of isolated uterus of mice pharmacodynamics of powder and ultramicro powder of Hirudo were compared. As a result, it indicates that ultramicro powder of Hirudo excels powder in the stimulation effect of isolated uterus of mice. At the same time it makes clear that new method of ultramicro pulverization has advantage and wide application foreground.
The quality standard of Cuijingzhiyun granules was studied. Applying TLC to indentify Herba Leonuri, Rhizoma Chuanxiong, Radix Angelicae Sinensis, Fructus Aurantii, Using HPLC to determine the content of ferulic acid of Rhizoma Chuanxiong and Radix Angelicae Sinensis. The methods are accurate and quick, and can be used for the quality control of Cuijingzhiyun granules.
引文
1．陈留村．流产药物的研究现状．新药与临床，1993，12(6)：357
2．廖爱华．米非司酮的作用机理及临床应用．实用妇产科杂志，1994，10(1)：15
3．宋韬．中药配合米非司酮与米索前列醇终止早孕的临床观察．四川中医，2001，1(9)：481
4．刘琼珠．药物流产安全性的研究近况．右江医学，2001，29(5)：421
5．王桐生，彭珊英，龙子江．药物流产后出血的中药治疗研究近况．承德医学院学报，2001，18(2)：160
6．张婷婷，刘昌官，吴敦序等．中药祛膜汤加强抗早孕的实验研究．生殖与避孕，1997，17(6)：347
7．张彩萍．中药生化汤配合米非司酮、米索前列醇抗早孕临床效果分析．中草药，1998，29(8)：547
8．贾玲，吕向华，楚金婷，等．复方中药及米非司酮与米索前列醇配伍抗早孕的研究．河南诊
断与治疗杂志，2001，15(2)：100
9．蒋蕙贞，黄艳仪，张立冬．祛瘀止血汤对米非司酮的促进作用．广州中医药大学学报，2002，19(1)：15
10．药典委员会．中华人民共和国药典．2000年版(一部)．北京：化学工业出版社，2000
11．阴健，郭力弓．中药现代研究与临床应用(1)．北京：学苑出版社．1993：555
12．国家中医药管理局《中华本草》编委会．中华本草．三册．上海：上海科技出版社
13．周秀佳．益母草类中药的研究概况和进展．中草药，1998，29(6)：415
14．黄泰康．常用中药成分与药理手册．下册．北京：中国医药科技出版社．1994：1484
15．石米扬．昌兰芳红花、当归、益母草对子宫兴奋作用的机理研究．中国中药杂志．1995，20(3)：173
16．刘春宇，唐丽华．顾振纶．中国当归的化学成分和药理作用研究概况．中国野生植物资源．1997，16(3)：12
17．黄伟晖，宋纯清．当归的化学和药理学研究进展．中国中药杂志，2001，26(3)：147
18．叶建红．川芎当归的药理作用与临床运用体会．天津中医，2002，19(4)：54
19．杨东焱，丁永辉．红花对大鼠平滑肌点活动的影响．甘肃中医学院学报，2000，17(1)：15
20．满伟．莪术油药理研究及临床应用进展．时珍国医国药，2000，11(7)：663
21．郑有顺．中医药药理与应用[M]．北京：军事医学科学出版社．1999：248
22．刘友平，秦春梅，鄢丹．β-环糊精包合物在药学领域中的应用进展．中草药，2003，34(7)：附4
23．超微粉(细胞破壁)粉碎技术研究资料汇编(中药专集—)．成都：4
24．关天增，雷敬卫，郑艳丽．浅谈超微粉碎．中国中药杂志，2002，27(7)：299
25．张保献，逵应坤，冯青然．同精制方法对苦参水提取液中苦参总生物碱含量的影响．中国中药杂志，2000，25(10)：607
26．彭维．枳实和枳壳中保健有效成分的含量分析．广西轻工业，1996，(11)：29
27．姜舜尧．益母草药材中水苏碱成分的高效液相色谱法分析．药物分析杂志，2001，21(4)：243
28．周世玉，徐智明．薄层扫描法测定益母草膏中盐酸水苏碱的含量．华西药学杂志，1999，14(5-6)：395
29．郭孝武，杨锐．不同频率超声提取对益母草总碱提出率的影响．中国医院药学杂志，1999．19(8)：465
