【作者】 李晓燕；

【导师】 刘守信； 张永锋；

【作者基本信息】 河北科技大学 ， 化学工程， 2014， 硕士

【摘要】 尿路感染(urinary tract infection,UTI)是泌尿系统的常见病、多发病,主要依靠致病菌侵入尿路,逆行向上感染,黏附尿路上皮,分泌毒素等致病。由于感染可累及尿道、膀胱、肾盂及肾实质,且不易定位,故临床上统称为泌尿系统感染,属于中医理论中的淋证。泌尿清淋片处方由柴胡、黄芩、萹蓄、大黄、苦参、车前子、乌药七味中药组成,为临床经验方,其功能为疏解肝经气滞,清化下焦湿热,临床用于治疗急性下尿路感染。本课题以传统中医药理论为指导,结合方中药味的性质,按照《药品注册管理办法》和新药研制的相关技术要求对泌尿清淋片的制备工艺和质量标准进行了研究。制备工艺研究:1、提取溶剂筛选:根据处方中药味的理化性质及文献报道并采用单因素试验法筛选了各药味的提取溶剂。确定柴胡、大黄及乌药采用乙醇提取;萹蓄、车前子、苦参采用水提取;黄芩单独提取制备黄芩苷。2、工艺优选:本着节约成本、利于环保的原则,按着提取溶剂将各药味合并,分别进行正交试验考察及方差分析,并进行验证试验,优选生产工艺。根据工艺优选结果确定:柴胡、大黄、乌药采用70%乙醇提取2次,第一次8倍量,第二次6倍量,每次2小时;萹蓄、车前子、苦参采用加9倍量水提取2次,第一次2小时,第二次1.5小时;黄芩采用水提取3次,时间为2、1、1小时,加水量为第一次10倍量,第二、三次为8倍量。将提取液加酸进行保温结晶,制备黄芩苷。3、成型工艺:对片剂的成型工艺进行了考察,明确了湿法制粒的辅料用量,粘合剂乙醇浓度及颗粒烘干时间等参数。经过3批中试试验,结果表明工艺稳定可行。质量标准研究:按照新药技术要求,建立了柴胡,苦参,大黄,乌药4味药材的薄层鉴别方法;进行了重金属及微生物检查,采用高效液相色谱法测定了黄芩中有效成分黄芩苷的含量,苦参中苦参碱的含量,并进行了方法学考察,结果表明方法简便,重复性良好,可以作为泌尿清淋片的质量控制方法。更多还原

【Abstract】 The urinary tract infection(UTI)is a common and frequently-occurring disease of urinary system which causes disease through pathogenic bacteria invading the urinary tract, retrograding infection,upward adhesion epithelium of the urinary tract and secreting toxins. As the infection involves the urethra, the bladder, the renal pelvis and the renal parenchyma, and is not easy to be located, the UTI is referred to urinary system infection in clinical which belongs to "water" in Chinese medicine theory.Miniaoqinglin Tablet is the sixth category of national TCM drug classification and the prescription contains seven herbs, including Bupleuri Radix,Scutellariaeradix, Polygoniavicularis Herba. and so on, is used in the treatment of acute urinary tract infections in the clinical.According to the measures for the administration of drug registration and the technology related to developing new medicine, this reaearch mainly study on the preparation technology and the quality standard of the Miniaoqinglin Tablet guided by the traditional Chinese medicine theoty.The preparation process study:1. The extraction solvent study: The extraction solvent was screened according to the crude drug physichemical properties and the lieterature. The extraction solvent of Bupleuri Radix,Rhei Radixet Rhizoma,Linderae Radix was ascertained ethanol. The extraction solvent of Polygoni Avicularis Herba,Plantaginis Semen,Sophorae Flavescentis Radix was ascertained to water. The baicalin was prepared from Scutellaria baicalensis separately.2.Process optimization: Based on the principle of cost saving and environmental-ly frie ndly, the various ingredients were merged according to the extraction solvent. The orthog onal experiment and investigation and analysis of variance were carried out respectively. According to the validation test, the production process was optimized. The optimization results of Bupleuri Radix,Rhei Radix et Rhizoma,Linderae Radix were ascertained as follows: extracting for two times, each time for 2 hours, adding 8 times amount of 70% ethanol for the first time and adding 6 times amount of 70% ethanol for the second time. The optimization results of Polygoni Avicularis Herba, Plantaginis Semen, Sophorae Flavescentis Radix were determined as follows: adding 9 times amount of water, extracting for two times, the first 2 hours and the second 1.5 hours. The extraction of Scutellaria baicalensis with water was determined as follows: extracting for three times, adding 10 times amount for 2 hours for the first time, adding 8 times amount for 1 hours for the second and the third times. The baicalin was prepared by acidizing to the extract for thermal insulation and crys-tallization.3. The preparation of molding process: The preparation of molding process was studied and determined to the excipients dosage of wet granulation, the ethanol concentration of binder agent, the time of grain drying and other parameters. After the 3 batch of pilot test, the results showed that the process is stable and feasible.The quality stanard study:According to the new drug technical requirement, the TLC method was established for the Radix Bupleuri, Sophoraflavescentis Radix, Rhei Radix Et Rhizoma and Linderae Radix. The content of heavy metal and microbial limits was studied. The Baicalin content in Scutellariaeradix and the Matrine content in Sophoraflavescentis Radix were determined by using HPLC. The results showed that the method was simple and has good reproducibility, and it can be used to control the quality of Miniaoqinglin Tablet.更多还原