注射用丹红（粉针）的药学研究

【作者】 罗海燕；

【导师】 谢秀琼；

【作者基本信息】 成都中医药大学 ， 中药学， 2004， 博士

【摘要】 中药注射剂是治疗急症较好的剂型，近10余年，随着中药注射剂的产销量快速增长，临床上的应用也显著增加的同时，有关中药注射剂的产品质量问题和临床安全问题的报道也逐渐增多。丹红注射液为活血化瘀类药物，是中药丹参、红花复方制剂，用治冠心病心绞痛。针对其多年临床应用中暴露出的问题，以之为样本，进行工艺改进和剂型改革，制成注射用丹红(粉针)，探索中药注射剂研发新思路，提高制剂的有效性、安全性和稳定性。采用溶剂提取、树脂纯化等工艺，借鉴西药冻干粉针技术，系统研究了丹参、红花中间体的制备及其质量标准，以及冻干成型工艺、粉针质量评价，成功地研制了注射用丹红(粉针)，符合中药注射剂研究的技术要求，达到了课题设计目的。 针对丹参、红花原生有效组分丹参总酚酸和红花总黄酮，并以此作为评价指标，分别进行了较低温的提取、分离研究。 根据丹参总酚酸不耐热的的性质，采用乙醇渗漉的提取方法，考察了乙醇浓度、用量、渗漉速度对提取效果的影响，确定了丹参乙醇渗漉提取工艺条件。红花总黄酮不宜长时间高温加热，采用水温浸提取，考察了温浸温度和次数、水的用量，确定了红花的水温浸提取工艺条件。 通过比较不同除杂方法，筛选出丹参、红花提取液大孔树脂精制工艺，考察了树脂型号、上样速度、最大上样量、乙醇洗脱浓度及用量。确定了大孔树脂精制的工艺条件，再以膜分离法除去大孔树脂残留，分别得到丹参中间体和红花中间体。 进行了注射用丹红配液、除菌、骨架剂筛选、冻干工艺等研究。 从一般质量检查、含量测定、刺激性等方面对注射用丹红进行了初步质量评价。研究结果表明，通过新工艺的运用，显著提高了注射用丹红有效成分的含量，使可测成分总量超过了60％；同时，家兔腿肌肉刺激性试验、血管刺激性试验结果证明，注射用丹红刺激性明显降低，使用更安全；通过剂型改革，制成粉针固体剂型，避免了酚酸类有效成分在水中的氧化分解，制剂更稳定。 研究并建立了原料、中间体及成品指纹图谱检测标准，对该方法的稳定性、精密度及重现性等方法学进行了考察，结果均符合要求。同时对三者的指纹图谱进行了比较研究，相关性良好。更多还原

【Abstract】 Traditional Chinese Medicine (TCM) Injection as the important choice for the acute, serious and emergent diseases’ teatment, many problems often occur. The Danhong injection, which has the function of promoting blood circulation and removing blood stasis, is the complex prescription made up of 2 medicinal herbs, including radix salviae miltiorrhizae and flos carthami. Using the prescription as model, the project seeks the way and methods of improving the quality of TCM injection theoretically and practically and promotes the development of TCM injection.In this project, aim at the problems proved in the clinic use, the freeze-dry form was chosen to promote its efficacy, safety and stability.In the study of Danhong for injection, based on the characters of active substance, new extracting and separating techniques was applicated. In optimum condition of extraction and separation with macroporous resin, two semi-products, named polyphenolic acids and total flavonids which are active principles, were obtained from separated herbs.The freeze-dry method is defined with the preparation confecting liquid, the excipient and the freeze-dry conditions.Exploring and establishing methods of quality control of semi-products and final products is very important means to ensure quality of final products. Characters, analyses of active components, safety have been studied for quality evaluation of semi-products and final products.The chromatographic fingerprint was established for botanical drugs, their semi-products and final products. High performance liquidchromatography was carried out under optimized experimental condition by means of gradient elution and UV detection. The method is specificity, reproducibility and applicability.The analysis of the components, stimulation and hemolysis for the powder for injection indicates that the new process can promote the content of effective components, reduce the similation and increase the stability.更多还原