【作者】 陈昌利；

【导师】 魏道智； 冉晓辉；

【作者基本信息】 福建农林大学 ， 草业科学（专业学位）， 2012， 硕士

【摘要】 为提高康艾扶正制剂中药物对湿、氧稳定性,提高生物利用度,简化生产工艺,丰富临床剂型,特地进行康艾扶正成液体胶囊的研制。康艾扶正液体胶囊由灵芝、黄芪、刺梨、熟地黄、女贞子、淫羊藿、半夏(姜制)等组成,具有散结消肿,益气解毒,合胃安神的功能。主要用于减少肿瘤放化疗引起的血小板减少,白细胞下降等,还可用于提高机体免疫力,增进食欲,预防呕吐和失眠等的辅助治疗。本文主要就其制备工艺(提取工艺、成型工艺以及中试放大试验)、质量标准、稳定性等进行了初步研究。在中医药理论指导下,我们根据临床用药要求,结合处方中药物的现代药理学研究资料和处方中药物活性成分的理化性质,以干膏收率和黄芪甲苷(C41H68O14)含量为考察指标,通过正交试验优选出最佳提取工艺为：将灵芝粉碎成粗粉,与女贞子混合,加乙醇浸泡12h后,加8倍量乙醇回流提取二次,每次2h,滤过,药渣与其余黄芪等五味药材,加10倍量的水煎煮二次,每次2h。通过对康艾扶正液体胶囊进行的成型工艺研究结果表明：液体胶囊剂在pH为4.5-5.0之间稳定,内含物含水量在24%左右达到平衡,充填温度在50-60℃时选用苏州植物胶囊进行填充,通过2次锁口,密封性好,且无渗漏,主药成分含量稳定。通过中试放大实验,证明本工艺稳定、可控,重现性好。通过质量标准研究证明：在薄层色谱鉴别中,灵芝、黄芪、淫羊藿、女贞子四味药材的专属性好。黄芪甲苷含量测定结果显示,10批处方样品的含量均高于0.10mg,根据药典对黄芪甲苷含量的规定和综合本制剂含量测定结果,最后将含量限度修订为每粒含黄芪以黄芪甲苷计不低于0.14mg。成品微生物限度检查合格。通过加速稳定实验证明：在考察期内,康艾扶正液体胶囊外观性状良好,且密封性好,无渗漏,经测定,主药成分黄芪甲苷含量稳定,质量无显著性变化。从上述研究结果,可以得出结论：康艾扶正液体胶囊剂制备工艺科学、合理、可行；质量标准可控；成品性质稳定。更多还原

【Abstract】 In order to improve drug stability against wet and oxygen, to enhance its bioavailability, to simplify its streamline producing processes, and to enrich clinical forms of drug, pharmacal studies were carried out specifically on the Kang’aifuzheng liquid capsule in this thesis.Kang’aifuzheng capsule, which is composed of Ganoderma lucidum,Astragalus, Prickly Pear, Rehmannia, Fructus Ligustri Lucidi,Epimedium, Pinellia (Ginger prepared), has the function for benefiting healthy, disintoxicating, relieving congestion, subsiding the swelling, raising the stomach, and calming the nerves.So it is used mainly as adjunctive therapy in cases of white blood cell dropping and blood platelet reduction caused by tumor chemotherapy or radiotherapy, and in cased for enhancing the immunity function, promoting appetite, preventing vomiting or losing sleep, and so on. A preliminary study had been taken here mainly on the capsule’s preparation crafts (including extraction craft, formation craft as well as pilot enlargement experiment), on its quality specification, and on its stability.Guided by the theory of traditional Chinese medicine and according to clinical requirements, considering both the information of modern pharmacological research and the nature of active ingredients in the prescribed drug, and taking dry extract rate and astragaloside (C41H68O14) content as index, the best extraction process was filtered out using an orthogonal design method:crushed the Ganoderma lucidum into meal,then mixed with Fructus Ligustri Lucidi,soaked them in ethanol for 12 hours, then added with ethanol at the amount of 8 times, applied reflux extraction twice every two hours;then after filtering, the residues, together with the other five herbs, added in 10 times amount of water and boiling twice, each two hours.According to the craft research on molding process, the liquid capsules keep stable in pH 4.5-5.0, reach equilibrium at the moisture content of about 24%, achieve good sealing and no leakage and stability of the main drug ingredients by filling using Suzhou plant capsule at a temperature between 50-60℃ with 2 locking processes.According to the pilot enlargement experiment, it proves that this process is stable, controllable, and of good reproducibility.In the studying of quality standards, the thin layer chromatography (TLC) method was adopt to discriminate Ganoderma Lucidum,Astragalus, Epimedium,and Ligustri Lucidum, separately. Determination results show that the contents of astragaloside in all of the 10 samples were higher than 0.10mg. According to the content limits provided in the Pharmacopoeia and taking the determination results into consideration, a standard of astragaloside content for each piece of capsule was set at the minimum of 0.14mg. Inspection on the microbial limits of the production is also up to standards.It was also testified by accelerated stability inspection:throughout the period, Kang’aifuzheng liquid capsules kept good appearance, sealed well, and were free of leakage. The main ingredient, astragaloside, was tested to be stable, and without a marked change in quality.All of these characters have suggested that this preparation process for Kang’aifuzheng liquid capsule is rational, reasonable and feasible, the quality standard is controllable, and the products are stable.更多还原