痛风颗粒制剂学、质量标准及稳定性研究

【作者】 刘振丽；

【导师】 李云谷；

【作者基本信息】 北京中医药大学 ， 中药制剂学， 2003， 硕士

【摘要】 痛风是嘌呤代谢紊乱及/或尿酸排泄减少所引起的一组疾病。其临床特点为高尿酸血症，特征性反复发作的急性关节炎、痛风石沉积、痛风石性慢性关节炎和关节畸形，常累及肾脏引起慢性间质性肾炎和尿酸性肾结石形成。目前，西医对本病的治疗并不理想。痛风颗粒处方为全国著名老中医朱良春医生临床应用多年，行之有效的经验方。由制何首乌、土茯苓、威灵仙、重楼、徐长卿、蚕砂和车前子组成，具有清热解毒，泄化浊瘀，消肿定痛的功能。用于治疗痛风性关节炎。本课题对临床处方按国家中药新药申报要求，选择颗粒剂型在制剂学、质量标准和稳定性方面进行研究。制剂学研究部分：对处方进行方药分析，随方确定了有效成分。根据有效成分的性质，设计生产工艺路线，并对影响生产的各种因素及技术条件进行优选。1.对提取工艺条件进行了优选。以丹皮酚得量为指标，确定了徐长卿中丹皮酚的提取工艺条件；以包结率为指标，对丹皮酚的(-环糊精包结工艺进行了正交优选；以正丁醇萃取物得率为指标，对蚕砂等三味药的水提取工艺条件进行了正交优选；比较了水煎煮、乙醇回流和乙醇渗漉法对制何首乌中2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（二苯乙烯苷）的提取率，并考察了浓缩干燥过程对其影响；以二苯乙烯苷含量为指标，对制何首乌等四味药的醇提取工艺技术条件进行了正交优选。2.在醇沉净化工艺中，以正丁醇萃取物含量为指标，确定水提取液浓缩的相对密度、乙醇的浓度。3.在浓缩与干燥工艺的优选中，考察了温度、湿度及60Co-γ射线辐射对二苯乙烯苷稳定性影响，确定了醇提取液浓缩、真空干燥的条件；以干浸膏粉含水量、溶解性、正丁醇萃取物含量为指标，确定了水提醇沉液浓缩、真空干燥的条件。4.在制剂成型工艺研究中，确定了辅料的种类和用量。进行了各优选条件的工艺验证。4.进行了三批中试验证。质量标准的研究部分：1.采用TLC法,以对照品、对照药材或处方中经鉴定的药材为对照，建立了制剂中制何首乌、土茯苓、威灵仙、重楼和徐长卿的定性鉴别方法。2. 采用高压液相色谱法，测定了不同地区十个批次制何首乌中二苯乙烯苷含量。3. 采用HPLC法，建立了成品中二苯乙烯苷的含量测定方法, 制定了成品颗粒质量标准。4. 对何首乌药材的HPLC/UV指纹图谱分析方法进行了研究，并与同科属药材及伪品图谱进行了比较。稳定性研究部分：1.对三批中试样品进行了初步稳定性考察。2.应用动力学原理，选择制剂中对湿热不稳定的制何首乌中的二苯乙烯苷、易挥发的徐长卿中的丹皮酚为指标，测定痛风颗粒于不同温度、放置不同时间含量的变化，预测痛风颗粒室温有效期。更多还原

【Abstract】 Goat is a group of diseases that caused by urine metabolic disturbance and/or urine acid goathypoeccrisis. The characteristics of goat are hyperuricemia, characteristic recurrent acute arthritis, gouty tophus sedimentation, chronic arthritis and joint deformity, which cause chronic nephritis and uratic nephrolithiasis. Up till now, there is no optimal remedy for goat in western medicine.The prescription of Tongfeng granule was a proved effective recipe that has been used for many years by doctor Zhu Liang-chun. It consists of prepared Radix Polygoni Multiflori, Rhizoma Smilacis Glabrae, Radix Clematidis, Rhizoma Paridis, Radix Cynanchi Paniculati, Bombyx Mori and Semen Plantaginis. The efficiencies of Tongfeng franulea are clearing away heat and toxic material, purging turbid urine, subduing swelling and alleviating pain, which is used to treat gouty arthritis.This work is to study processing technology, quality standard and stability of "Tongfeng franulea" according to the demands of new drug of Chinese medicine. Preparation: 1. Optimize extracting method. The best factors for extracting paeonol from Radix Cynanchi Paniculati were made certain; the best condition for paeonol inclusion with (-CD was studied; the factors decocting Radix Cynanchi Paniculati, Bombyx Mori and Semen Plantaginis as well as extracting 2,3,5,4’-stilbene glucoside from Radix Polygoni Multiflori etc. by alcohol were selected by orghogonal test; Three methods for extracting 2,3,5,4’-stilbene glucoside from Radix Polygoni Multiflori were compared, and the influence of condensation and drying process on the content of 2,3,5,4’-stilbene glucoside was studied. 2. Optimize dissociationg, purification, condensation and drying method. The content of n-Butanol and 2,3,5,4’-stilbene glucoside as well as the solubility of the granule were selected as the indexes of option process. The stability of 2,3,5,4’-stilbene glucoside under high temperatures and 60Coγ-ray radiation were tested. 3. Optimize preparation process for the granule. The species as well as the amount of supplementary materials were determinate. Quality Standard: 1. The characteristic compositions or standard crude drugs were taken as the indexes with TLC to identify the quality of prepared Polygoni Multiflori, Rhizoma Smilacis Glabrae, Radix Clematidis, Rhizoma Paridis and Radix Cynanchi Paniculati. 2. The contents of 2,3,5,4’- stilbene glucoside in Prepared Radix Polygoni Multiflori from different areas were detected by HPLC . 3. The content of 2,3,5,4’-stilbene glucoside in the granule was determined with HPLC. 4 HPLC was used to establish HPLC fingerprint analysis for Polygoni Multiflori. <WP=7>Stability: 1. The preliminary stability of the granule was tested for three months after made in the factory. 2. The contents of 2,3,5,4’-stilbene glucoside and paeonol in the granule were detected after the granule was undergoing high temperatures for different times, and the expiry date of Tongfeng granule at chamber was calculated.更多还原