【作者】 钱平；

【导师】 刘志辉；

【作者基本信息】 南京中医药大学 ， 药剂学， 2010， 硕士

【摘要】 冠状动脉性心脏病(冠心病)是一种由冠状动脉供血能力下降引发的心肌缺血性疾病,临床常表现为心绞痛,可伴有心律失常,严重者可导致心力衰竭、心肌梗死以及心脏骤停,危害巨大。目前治疗冠心病的化学药物长期使用易导致不良反应和耐受性,且禁忌症多,具有一定局限性。冠心平颗粒处方为江苏名中医李七一教授的经验方,由酒黄精、三七、当归、瓜萎皮和甘松组成,用于治疗气阴两伤、痰血淤阻型冠心病,临床应用多年,效果显著。本课题按照国家中药新药申报要求选择颗粒剂型对临床处方进行了制剂工艺、质量标准研究和稳定性考察。制剂工艺研究部分：根据中医药理论、各药味主要有效成分的性质设计制剂工艺路线并对工艺条件进行优选。1.对酒黄精的提取工艺进行了药效学评价,并以多糖提取率和正丁醇萃取物得率的综合评分为指标,对酒黄精的提取工艺条件进行了优化；结果酒黄精水提液经醇沉精制处理后药效降低,故提取工艺选择水提取,不进行醇沉处理；优化后的提取工艺条件为：提取3次,每次8倍量水,提取0.5h。2.采用共水蒸馏法提取当归、甘松挥发油,以挥发油量和提取液中阿魏酸含量为指标,确定了提取时间为3h；使用p-环糊精对提取的挥发油进行了包合处理,以挥发油包合率为指标,对包合过程的影响因素进行了单因素考察,并采用正交设计优化工艺条件,结果为每1mL挥发油,以4倍体积乙醇溶解后,加入至10gβ-环糊精的饱和水溶液中,搅拌3h,溶解挥发油所用乙醇量对包合效果具有显著性影响。3.以阿魏酸含量为指标,对瓜蒌皮、当归、甘松的提取工艺条件进行了优化,结果为：提取2次,每次加9倍量水,提取0.5h。4.以三七皂苷R1、人参皂苷Rgl、人参皂苷Rb1提取率为指标,采用均匀设计对三七的提取工艺条件进行了优化,结果为：以70%,60%的乙醇各回流提取1次,溶剂用量分别为8倍量,10倍量,每次回流提取1h。5.以阿魏酸转移率和乙醇消耗量为指标,对瓜萎皮、当归、甘松提取液的醇沉精制工艺条件进行了优化,结果为：在温度70℃,真空度为0.08-0.09Mpa条件下,药液浓缩至相对密度1.10(60℃测),加乙醇至含醇量达60%,静置12h,滤过。6.对制剂成型工艺进行考察,确定了制粒的工艺条件,结果为：以糊精为辅料,用量为浸膏粉重量的50%,采用干法制粒技术,主要参数为：喂料电机转速40 r·min-1,压轮电机转速7 r·min-1,压轮间距0.3mm,整粒电机转速20-25 r·min-1。7.进行了中试研究,结果表明制订的工艺具有可操作性,基本稳定。质量标准研究部分：采用薄层色谱、高效液相色谱等方法对制剂进行了定性鉴别、含量测定方面的研究,制定了质量标准。1.按照2005年版《中国药典》的规定,对所使用的原料药材进行了鉴别和检查。2.采用薄层色谱法,建立了制剂中酒黄精、三七、当归、瓜萎皮和甘松的定性鉴别方法。3.采用高效液相色谱法,建立了制剂中三七皂苷R1、人参皂苷Rg1、人参皂苷Rbl和阿魏酸的含量测定方法,并制订了成品颗粒的质量标准。4.根据颗粒剂通则规定,对制剂进行了检查,结果符合规定。稳定性考察：对制剂进行了初步稳定性考察。更多还原

【Abstract】 Coronary artery Heart Disease is a form of Myocardial Ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Angina is the most common clinical manifestation of Coronary artery Heart Disease and may accompany by arrhythmia. Severe Coronary artery Heart Disease may cause heart-failure, myocardial infarction and sudden cardiac arrest. During the treatment, the long-term using of chemicals tends to cause adverse reactions and tolerance, and there also many contraindications to these chemicals, so chemical medication have limitations.The prescription of Guanxin-ping granule was a proved effective recipe that has been used for many years in the treatment of Coronary artery Heart Disease by the famous doctor of Traditional Chinese Medicine——Li Qi-yi.The recipe was made up of Rhizoma Polygonati Praeparata, Radix Et Rhizoma Notoginseng, Radix Angelicae Sinensis, Pericarpium Trichosanthis, Radix Et Rhizoma Nardostachyos. This project is to study preparation technology, quality standard and stability of Guanxin-ping granule according to the demands of new preparations for Traditional Chinese Medicine.Preparation Section:According to the theory of Traditional Chinese Medicine and the physicochemical property of the active ingredient, preparation process has been designed.1. The extracting technology of Rhizoma Polygonati Praeparata has been evaluated by pharmacodynamic method. Using the extraction ratio of polysaccharides and the yield of n-butanol extaction as indexes, extracting method of Rhizoma Polygonati Praeparata has been optimized. The results show that the pharmacological effects of the extraction are declined after refined by alcohol precipitation. So Rhizoma Polygonati Praeparata is unfit to refine by alcohol precipitation after extracted by water. The optimized extraction technology is:extracting 3 times, using 8-fold volume of water for 0.5 hour each time.2. The distilled oil of Radix Angelicae Sinensis and Radix Et Rhizoma Nardostachyos have been extracted by steam distillation method. Using the volume of distilled oil and ferulic acid content in the extraction as indexes, the extraction time has been made certain; Distilled oil have been included by P-cyclodextrin. Using the inclusion percentage as the index, possible factors affecting the inclusion procedure have been investigated by single factor experiments, and then the technology has been optimized using orthogonal design. The result is:1mL distilled oil being resolved in 4 times alcohol then dropping it into 10gβ-cyclodextrin’s saturated water solution and stirring for 3 hours. The volume of solvent which used to resolve the distilled oil has significant influence on inclusion effect.3. Using the content of the ferulic acid as the index, extracting method of Pericarpium Trichosanthis, Radix Angelicae Sinensis and Radix Et Rhizoma Nardostachyos has been optimized. The result is:extracting 2 times, using 9-fold volume of water for 0.5 hour each time. 4. Using the extraction ratio of Notoginsenoside R1, ginsenoside Rg1 and ginsenoside Rb1 as indexes, extracting method of Radix Et Rhizoma Notoginseng has been optimized using uniform design method. The result is:extracting 1 time with 70% and 80% alcohol respectively, using 8-fold volume of 70% alcohol and 10-fold volume of 80% alcohol for 1 hour each time.5. Using the transfer percent of the ferulic acid and the dose of ethanol as indexes, the alcohol precipitation process of Pericarpium Trichosanthis, Radix Angelicae Sinensis and Radix Et Rhizoma Nardostachyos’water extracts has been studied. The result is:the temperature is 70℃, the vacuum is 0.08～0.09MPa, the relative density of the extrction is 1.10(determined under 60℃), adding alcohol to the extraction and making it a 60% alcohol solution, then letting it stand for 12 hours.6. Preparation process for the granule has been optimized.7. Pilot-scale experiments have been carried out using the stuied preparation process.Quality Standard Section:1. According to the Chinese Pharmacopoeia (edition2005), herbs used for preparation has been checked and identified.2. The identification methods of the herbs in the preparation have been established using TLC.3. The Determination methods of ferulic acid, Notoginsenoside R1, ginsenoside Rg1 and ginsenoside Rb1 have been established using HPLC.4. According to the general principles for granule, the preparation has been checked and the results met the requirement of Chinese Pharmacopoeia.Stability Section:The preliminary stability of the preparation has been studied.更多还原