克咳口服液制备工艺及质量标准研究

发布时间：2018-06-03 15:53

本文选题：克咳口服液 + 制备工艺　；参考：《北京中医药大学》2017年硕士论文

【摘要】："克咳口服液"是针对贵州益佰制药股份有限公司已经上市产品"克咳胶囊"进行二次开发的品种。具有止咳、定喘、祛痰的功效,在治疗各种咳嗽、急慢性支气管炎、支气管哮喘、老年咳喘具有显著疗效。适用于上呼吸道感染引起的咳嗽、支气管哮喘、急慢性支气管炎、咽喉炎、抽烟过量引起的咳嗽、老年咳喘等症状,对急症重病、顽固频繁咳嗽尤为适用。胶囊剂型虽然有其服用量小,便于携带,能掩饰不良气味等优点,可是对于食道较狭小、胃肠道功能较弱的儿童和老人而言,有服用不便、疗效发挥较慢等缺点。于是在疗效不变的基础上,对原处方进行了二次开发,根据处方中各药的理化性质和企业生产条件,对克咳口服液的制备工艺进行了研究,并基于中试产品对其质量标准进行了初步研究。在制备工艺方面,以麻黄中的盐酸麻黄碱、罂粟壳中的吗啡,甘草中的甘草酸等指标性成分与出膏率相结合,采用正交实验法,对处方中罂粟壳、麻黄,甘草、莱菔子、桔梗、石膏、苦杏仁的提取工艺分别进行了考察最终获得最优提取工艺为:罂粟壳粉碎成粗颗粒,麻黄切段,加入10倍量的酸性水溶液(用10%盐酸溶液调pH值至3左右)浸泡1.5小时后,煎煮两次,每次煎煮1.5小时。苦杏仁中所含的苦杏仁昔水解生成的氢氰酸,具有止咳平喘作用,但苦杏仁苷易被本身所含的苦杏仁酶分解,在煎煮之前蒸30分钟的方法,最方便实用、而且灭酶效果较好。传统的石膏煎煮方法为先煎,据资料考证石膏先煎并不科学,因为煎煮时间的长短并不能影响石膏的溶度积,煎煮时间过长,石膏会糊于其他药材表面,影响其他成分溶出,故采用石膏用300目的滤布包裹与其它药材合煎的方法。以甘草酸含量、出膏率为指标考察甘草等药材的最佳提取方法为:甘草、桔梗切片与莱菔子、石膏一起加8倍量水浸泡1.5小时,苦杏仁蒸30分钟后,与上述浸泡好的药材再加水至10倍量,煎煮两次,每次1.5小时。考察了醇沉工艺条件,其最佳条件为:药液混合,于60～70℃减压浓缩至相对密度为1.10(60℃测),放冷,加乙醇至含醇量为60%,静置18小时,滤过。滤液回收乙醇后,加入蒸馏水,产生大量的沉淀,经多次过滤,所得口服液依然不澄明,于是采用水沉法,并考察了水沉条件,结果最佳条件为:滤液回收乙醇,继续浓缩至相对密度为1.25(60℃测)的稠膏,加水至总量的60%,(4℃～8℃)冷藏72h,滤过。所得口服液较澄明,久置有轻摇即散沉淀。对所加入的辅料及用量进行了考察,确定含糖量为20%,防腐剂为苯甲酸钠加入的量为0.3%。口服液的pH是影响其稳定性的一个重要因素,当pH在4.50～5.50之间时,口服液相对稳定。最终确定了 "克咳口服液"的工艺参数,该方法方便、稳定、可行。在上述研究基础上,进行了三批中试放大研究,实验结果显示,工艺稳定可行。在质量标准研究方面,课题建立了口服液中麻黄、罂粟壳、甘草的薄层鉴别方法和盐酸麻黄碱和吗啡的HPLC检测方法,参照《中国药典》2010版制剂通则合剂项下规定建立了"克咳口服液"质量标准草案。综上所述,课题成功制备了"克咳口服液",并对其质量标准进行了初步研究。研制成为口服液,为该症患者带来了新的用药选择,为推广长期临床用药提供了科学依据,为下一步产品的申报奠定了基础。
[Abstract]:"Kusk oral liquid" is the two development of the "Keke capsule", which has been listed in the Limited by Share Ltd Limited by Share Ltd. It has the efficacy of relieving cough, asthma and expectorant. It is effective in treating various cough, acute and chronic bronchitis, bronchial asthma and senile cough and asthma. It is suitable for cough and bronchitis caused by upper respiratory tract infection. Guan Xiaochuan, acute and chronic bronchitis, pharyngitis, smoking excessive cough, senile cough, asthma and other symptoms, especially for acute severe disease, stubborn and frequent coughing. Although the capsule dosage form has its advantages of small dosage, easy to carry, can mask bad odor, but for children and elderly people with a smaller diet, weak gastrointestinal function, and the elderly, there are On the basis of the constant curative effect, the original prescription was developed for two times. Based on the physicochemical properties and production conditions of each prescription, the preparation technology of kought oral liquid was studied. Based on the pilot product, the quality standard was preliminarily studied. With ephedrine hydrochloride, morphine in the poppy shell and glycyrrhizic acid in licorice, the extraction technology of Papaver shell, ephedra, licorice, radish, Platycodon, plaster and bitter almond was finally obtained by orthogonal experiment. The optimum extraction technology was obtained, which was the crushing of poppy shell into coarse grain. Grain, ephedra cut section, add 10 times the amount of acid water solution (with 10% hydrochloric acid solution pH value to about 3) soak for 1.5 hours, decoct two times and decoct for 1.5 hours each time. The bitter almond in bitter almond is hydrolyzed with hydrocyanic acid, which has antitussive and antiasthmatic action, but bitter amygdalin is easily decomposed by its own bitter almond enzyme and steamed 30 before decocting. The method of minute is most convenient and practical, and the effect of enzyme extinguishing is better. The traditional method of plaster decocting is first decocted. According to the data, it is not scientific to decoct the gypsum first, because the length of the decocting time can not affect the solubility product of the gypsum, the time of decocting is too long. The gypsum will paste on the other medicinal materials and influence other ingredients to dissolve, so 300 orders of gypsum are used. The best extraction methods of Radix Glycyrrhizae, including glycyrrhizic acid content and extract rate, are as follows: Glycyrrhiza, Platycodon grandiflorum sliced with Raphani, gypsum with 8 times the water for 1.5 hours, after 30 minutes of bitter almond steaming, and then 10 times of water, two times and 1.5 small decocts. The optimum conditions of alcohol precipitation were investigated. The optimum conditions were as follows: mixture of liquid and liquid, concentrated at 60~70 C to 1.10 (60 degrees C), cooling, adding alcohol to alcohol content 60%, stating for 18 hours, filtration. After the filtrate was reclaimed, distilled water was added to a large amount of precipitation, and the oral liquid was still not clear, and the oral liquid was still not clear. The oral liquid was still not clear, so the oral liquid was still not clear, thereupon the oral solution was still not clear, thereupon the oral liquid was still not clear, thereupon the oral solution was still not clear, thereupon the oral solution was still not clear, thereupon the oral solution was still not clear, thereupon the oral solution was still not clear, thereupon the oral solution was still not clear, thereupon the oral solution was still not clear, thereupon the oral solution is still not clear, thereupon the oral solution is still not clear, thereupon the oral solution is still not clear, thereupon the oral solution is still not clear, thereupon the oral solution is still not clear, thereupon the oral solution is still not The water sedimentation method and the condition of water sedimentation were investigated. The optimum conditions were as follows: the filtrate reclaimed ethanol and continued to concentrate to the thickening ointment with relative density of 1.25 (60 degrees centigrade), adding water to 60% of the total amount, (4 ~ 8 c) refrigerated 72h, filtration. The oral liquid was clear, and the long set was scattered and precipitated. 20%, the amount of antiseptic to sodium benzoate as the amount of pH of 0.3%. oral liquid is an important factor affecting its stability. When pH is between 4.50 and 5.50, oral liquid is relatively stable. Finally, the technological parameters of "kought oral liquid" are determined. This method is convenient, stable and feasible. On the basis of the above study, three batch magnification studies have been carried out. The results showed that the technology was stable and feasible. In the study of quality standards, the TLC identification method of ephedra, Papaver shell, licorice and HPLC method for the detection of ephedrine hydrochloride and morphine in oral liquid were established, and the quality standard of "kought oral liquid" was set up according to the provisions of the general principles of Chinese Pharmacopoeia >2010. The "kought oral liquid" was successfully prepared, and its quality standard was preliminarily studied. It was developed into oral liquid, which brought new choice of drug for the patients, and provided scientific basis for the promotion of long-term clinical medication and laid the foundation for the application of the next product.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.6;R286.0

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