双参平肺颗粒制剂工艺与质量标准研究

发布时间：2018-05-13 01:15

本文选题：双参平肺颗粒 + 制备工艺　；参考：《南京中医药大学》2017年硕士论文

【摘要】：近年来,随着中国经济飞速发展,城市污染进一步加重,导致空气质量直线下降。污水、汽车尾气、雾霾无疑加快了生态环境恶化的步伐,严重影响到人体呼吸健康,肺部疾病成为现代社会中的一种高发病。双参平肺方源于临床治疗肺痹的经验总结,由人参、丹参、知母、天冬、橘红、地骨皮、桑白皮、甘草八味药组成,制成具有清肺润燥,镇咳止呕之功效的颗粒剂,用于治疗心火刑肺,咳嗽喘呕,痰涎壅盛,胸膈痞满。本课题全面系统的综述了双参平肺颗粒的工艺及质量标准研究。论文主要分为五个部分:第一部分文献综述:查阅文献并综述了双参平肺颗粒处方方解、组方药物的化学成分及药理作用等。第二部分双参平肺颗粒制备工艺研究:针对组方药材不同药效成分分析,分别甄选合适的醇提和水提工艺。以丹酚酸B含量为评价指标,正交法优选人参、丹参醇提工艺;以芒果苷含量为评价指标,基于复方配伍优选知母提取工艺;以甘草酸含量为评价指标,正交法优选桑白皮、天冬、橘红、地骨皮、甘草水提工艺。同时,在双参平肺颗粒制备工艺研究中,通过组方拆方提取研究发现,知母中芒果苷可能与桑白皮中的成分形成缔合降低了芒果苷从药材中的转移率。因此,确定工艺为:取知母饮片,水提取二次,第一次加水12倍,第二次加水10倍,每次1.5小时,滤过,滤液合并,减压浓缩得浸膏一,备用;取人参、丹参二味饮片,加70%乙醇提取二次,第一次为6倍量,第二次为5倍量,每次1.5小时,滤过,滤液合并,减压浓缩得浸膏二,备用;药渣与其它五味药材合并,加水提取二次,第一次加水12倍,第二次加水10倍,每次1.5小时,滤过,滤液合并,减压浓缩得浸膏三,与上述浸膏一、浸膏二合并,混匀,减压浓缩至相对密度1.16-1.28(50℃)的稠膏,加入糊精及适量阿斯巴甜,混匀,制成颗粒,干燥、整粒,分装,即得。第三部分双参平肺颗粒质量标准研究:因为双参平肺颗粒属于新药研发,之前没有相关的质量标准研究,所以,以方中主要药效成分芒果苷与丹酚酸B为含量测定的主要成分并进行方法学研究,同时优选各味药材薄层鉴别方法,最终确定:以乙腈(A)-0.1%三氟乙酸水(B)系统梯度洗脱进行色谱分析,检测波长为245nm,柱温为30℃。该方法方便可靠,可同时测定丹酚酸B与芒果苷。第四部分双参平肺颗粒稳定性初步研究:对双参平肺颗粒进行了初步稳定性试验,结果表明,本品安全可靠,质量稳定。第五部分基于LC-MS-MS双参平肺颗粒溯源性初步研究:双参平肺颗粒甲醇提取,以甲醇-酸水系统为流动相进行液相分析,共选出21个峰,并进行方法学考察,实验证明,该指纹图谱方法具有较好的重复性、稳定性。采用中药指纹图谱相似度评价系统对不同批次样品进行相似度分析,结果表明,各批次样品均为0.95以上,说明双参平肺颗粒制剂工艺稳定。采用HPLC-DAD对制剂样品与药材样品进行检测后,将21个共有峰进行药材归属,并结合HPLC-MS进行成分确认,共找出制剂与药材中同时存在的31个成分。结论:通过双参平肺颗粒的制剂工艺研究、质量标准研究、稳定性初步研究、溯源性研究等,表明双参平肺颗粒工艺合理,质量可控,安全可行。
[Abstract]:In recent years, with the rapid development of China's economy and the further aggravation of urban pollution, the air quality has declined linearly. Sewage, automobile exhaust, and fog haze undoubtedly accelerated the pace of ecological environment deterioration, seriously affecting the health of the human body, and the lung disease has become a high incidence in modern society. The summary of the experience is made up of eight drugs of ginseng, Salvia miltiorrhiza, Anemarrhena, asemine, asparagus, tangerine, ground skin, mulberry skin, liquorice, and liquorice, which have the effect of clearing lung and relieving cough and antiemesis. It is used for the treatment of heart fire and lung, cough and vomiting, phlegm congestion and full chest diaphragm. This subject is a comprehensive and systematic review of the study on the technology and quality standard of double ginseng lung granules. The paper is divided into five parts: the first part of the literature review: consulting the literature and summarizing the prescription of double ginseng lung granule prescription, the chemical composition and pharmacological action of the prescription drugs. The second part of the preparation technology of the double ginseng lung Granule: according to the analysis of different medicinal ingredients in the herbal medicine, select the appropriate alcohol extraction and water extraction process. The content of phenolic acid B was the evaluation index, the orthogonal method was used to optimize the alcohol extraction process of ginseng and Salvia miltiorrhiza. With the content of mangiferin as the evaluation index, the extraction technology of Anemarrhena was optimized based on the compound compatibility. The extraction process of mulberry white skin, asparagus, orange, ground skin, and Glycyrrhiza was optimized by orthogonal method. It was found that mangiferin in the rhizoma Anemarrhena may be associated with the formation of the ingredients in the cortex Morus and reduce the transfer rate of mangiferin from the medicinal materials. Therefore, the process is as follows: extraction of Anemarrhena from Rhizoma Anemarrhena, two times of water extraction, 12 times of water in the first time, 10 times of water adding second times, filtration, filtrate merge, and decompression of extract one, Take ginseng, ginseng, Salvia miltiorrhiza two flavors and 70% ethanol to extract two times, 6 times for the first time, second times 5 times, 1.5 hours each time, filtrate, filtrate merge, decompress concentrated extract two, combined with other five herbs, two times, 12 times of water, second times, second times, filtrate and filtrate merge. Extract three of the extract, combined with the extract one, the extract two, mixing, mixing, reducing the pressure to the relative density 1.16-1.28 (50) thick paste, adding dextrin and a proper amount of aspartame, mixing, making particles, drying, whole grain, dividing, getting. Third parts of double ginseng lung granule quality standard study: because double ginseng lung granule is a new drug research and development, There is no related quality standard research, so the main component of the prescription, mangiferin and salvianolic acid B, is the main component of the content determination, and the method is studied. At the same time, the TLC identification method is selected. Finally, the chromatographic analysis is carried out with the gradient elution of acetonitrile (A) -0.1% three fluoroacetate water (B) system, and the detection wavelength is 245nm. The column temperature was 30 C. The method was convenient and reliable. A preliminary study on the stability of both salvianolic acid B and mangiferin. A preliminary study on the stability of double Shen lung granules in fourth parts: the preliminary stability test of double Shen Ping lung granules showed that the product was safe and stable. The preliminary Study on the traceability of lung granules in the fifth part was based on the double reference plane. The extraction of lung granule methanol was carried out with methanol acid water system as the liquid phase analysis. 21 peaks were selected and the method was investigated. The experiment proved that the fingerprint method had good repeatability and stability. The similarity evaluation system of Chinese traditional medicine fingerprint was used to analyze the similarity of different batch samples. The results showed that each batch was batch. All the samples were more than 0.95, indicating that the technology of double ginseng lung granule preparation was stable. After testing the preparation samples and medicinal materials by HPLC-DAD, 21 common peaks were assigned to the medicinal materials, and the components were confirmed with HPLC-MS. Conclusion: the preparation process of the preparation and the medicinal materials was found through the preparation process of double ginseng lung granules. Research, quality standard research, stability preliminary study and traceability study showed that the technology of Shuang Shen Ping lung granule is reasonable, quality controllable, safe and feasible.

【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R283.6;R286.0

【参考文献】