银翘蓝芩口服液的质量标准及靶动物安全性研究

发布时间：2018-12-21 09:56

【摘要】：银翘蓝芩口服液是中国农业科学院兰州畜牧与兽药研究所根据中兽医理论研制的预防和治疗禽呼吸道感染性疾病的复方中药口服液制剂,由金银花、连翘、黄芩、板蓝根等多味中药制成。对禽呼吸道感染性疾病有较好的防治效果,尤其是对鸡传染性支气管炎效果显著。本研究对银翘蓝芩口服液的质量标准进行研究,同时考察其对靶动物鸡的安全性,为其在临床安全科学的应用提供数据支持。1.根据《中国兽药典》2010年版要求,开展了制剂中主要中药材的薄层鉴别研究。对金银花、连翘、黄芩及苦参薄层鉴别时所用的点样量、展开剂、样品前处理方法、薄层板类型、显色方法等条件进行了优化,建立了上述4味中药材的薄层鉴别方法。研究结果显示,建立的方法斑点清晰、分离度高、简便易行、重复性好,阴性无干扰,可用于银翘蓝芩口服液的定性质量控制。2.根据《中国兽药典》2010年版要求,对银翘蓝芩口服液中绿原酸、黄芩苷及连翘苷三种主要成分进行含量测定,对其含量测定的方法学进行考察,结果显示建立的含量测定的方法系统适应性好,阴性对照无干扰,线性关系试验、精密度试验、加样回收率试验都符合方法学考察要求,且该方法操作简单,灵敏度高,结果准确,可用于银翘蓝芩口服液中主要有效成分的含量测定,为该口服的质量控制提供依据。3.按照《中国兽药典》2010年版一部要求,需对口服液的微生物污染程度进行评价。建立了微生物限度检查方法,并对方法进行验证。检查方法分别考察了菌液配置、培养基适应性和计数方法验证。控制菌(大肠埃希菌)检查方法同样考察了菌液配置、培养基适应性和计数方法验证。验证结果显示,可以采用上述验证过的常规法对该口服液进行微生物限度检查和控制菌检查。检查结果表明,银翘蓝芩口服液的微生物限度符合《中国兽药典》2010年版要求。4.对银翘蓝芩口服液中试产品进行稳定性考察,为其储藏条件和有效期的制定提供依据。稳定性考察包括影响因素试验、高温试验和高湿试验。在试验过程中检测绿原酸和黄芩苷的含量,并考察其性状、澄清度、相对密度、p H等变化。结果发现两种主要成分的含量没有明显变化,其它各项检测指标均无明显变化,稳定性较好,符合质量标准草案。5.依据兽药研究技术指导原则,开展银翘蓝芩口服液对靶动物鸡的安全性研究,为其临床应用的安全性提供数据资料。按银翘蓝芩口服液临床推荐剂量的1、3、5倍连续饮水给药7 d,给药后,采集血液和脏器,进行血常规、血液生化指标、脏器指数和组织病理学检查,并与对照组比较。试验结果显示,与对照组相比,各给药组鸡的血常规、血液生化、增重和脏器系数等指标差异均不显著(P0.05),各脏器组织未见明显的病理学变化。结果表明银翘蓝芩口服液饮水给药对靶动物鸡是安全的。
[Abstract]:Yinqiao Lanqin Oral liquid, developed by Lanzhou Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, is a compound Chinese medicine oral liquid for the prevention and treatment of infectious diseases in the respiratory tract of poultry. It consists of Lonicera Lonicerae, Forsythia, Scutellaria baicalensis, Radix Isatidis and other multi-flavor Chinese medicine made. It has good control effect on avian respiratory infectious diseases, especially on chicken infectious bronchitis. In this study, the quality standard of Yinqiao Lanqin oral liquid was studied, and the safety of Yinqiao Lanqin oral liquid was investigated to provide data support for its application in clinical safety science. 1. According to the requirements of the Chinese Veterinary Pharmacopoeia in 2010, TLC identification of the main Chinese medicinal materials in the preparation was carried out. The TLC identification methods of the four herbs were established, such as the sample quantity, the development agent, the sample pretreatment method, the thin-layer plate type, the color development method and so on, used in the TLC identification of Flos Lonicerae, Forsythia suspensa, Radix Scutellariae and Sophora flavescens. The results showed that the established method was characterized by clear spots, high separation, simplicity, good reproducibility and no interference, and could be used for qualitative quality control of Yinqiao Lanqin oral liquid. 2. According to the requirements of the Chinese Veterinary Pharmacopoeia in 2010, the contents of Lv Yuan, baicalin and suspensin in Yinqiao Lanqin Oral liquid were determined, and the methods of determination were investigated. The results showed that the established method had good adaptability, negative control had no interference, linear relation test, precision test and sample recovery test all met the requirements of methodological investigation, and the method was simple and sensitive. The results are accurate and can be applied to the determination of the main active components in Yinqiao Lanqin Oral liquid. According to the requirements of the Chinese Veterinary Pharmacopoeia in 2010, the degree of microbial contamination of oral liquid should be evaluated. The method of microbial limit examination was established and verified. The bacterial solution configuration, the adaptability of culture medium and the verification of counting method were investigated. Control bacteria (Escherichia coli) methods were also investigated in liquid configuration, medium adaptability and counting method. The results showed that the microbiological limit test and bacteria control test could be used in the oral liquid. The results showed that the microbial limit of Yinqiao Lanqin Oral liquid was in accordance with the requirements of the Chinese Veterinary Pharmacopoeia 2010 edition. 4. The stability of the pilot-scale product of Yinqiao Lanqin oral liquid was investigated to provide the basis for the formulation of storage conditions and validity period. The stability test includes influence factor test, high temperature test and high humidity test. The contents of Lv Yuan acid and baicalin were detected during the experiment, and the changes of their properties, clarity and relative density, p H were investigated. The results showed that the content of the two main components did not change obviously, and the other indexes were not changed obviously, the stability was good, and the content of the two main components was in accordance with the draft quality standard. 5. According to the technical guiding principle of veterinary drug research, the safety of Yinqiao Lanqin oral liquid to the target animal chicken was studied, which provided data for the safety of its clinical application. According to the clinical recommended dose of Yinqiao Lanqin Oral liquid, the patients were given drinking water for 7 days. Blood routine examination, blood biochemical index, visceral index and histopathology were collected and compared with those in the control group. The results showed that compared with the control group, the blood routine, blood biochemistry, weight gain and organ coefficient were not significantly different (P0.05), and no obvious pathological changes were found in the tissues of each viscera. The results showed that Yinqiao Lanqin oral solution was safe for target chickens.
【学位授予单位】：甘肃农业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：S853.7

【参考文献】