以蟾酥为例探讨“TOE”思路下的动物药质量控制内涵研究

The Raw Drug Material derived from the Animal origins (RDMA) is one of the three parts of Traditional Chinese Medicines (TCMs). The level and technology of its quality control are to be improved. Toad venom is not only one of the famous and expensive RDMA, but also one of 28 kinds of toxic TCMs to be required for special management issued by the State Council of the People’s Republic of China. It is widely used in the clinical practice with potent effectiveness, as one of the important ingredients of 88 preparations described in the "Drug Standards of Ministry of Health of China" and "Chinese Pharmacopoeia". Up to now, it is to be paid much attention to its poor quality of commercial toad venom because of the adulteration. So, it is helpful to establish the scientific quality control strategy of toad venom for the guarantee of its safety and effectiveness in the clinic. Moreover, the approach of quality control of whole RDMA industry is discussed taking toad venom as a case. The detailed investigations are as followed: the studies on the quality control strategy of toad venom and the key factors affecting its quality, such as origin species, processing and etc, are carried out under the guidance of totality-of-the-evidence (namely TOE). The samples prepared from the different toad species are compared to find the marker proteins or peptides as well as small molecules including bufadienolides and indole alkaloids employing the chemical, pharmacological techniques and proteomics. Based on the obtained data, the improved quality control methods are established for the standardization of the processing and manufacturing of toad venom.

动物药是中医药三大组成部分之一，其质量控制技术和水平亟待提高。蟾酥为我国贵重动物药品种，也是国务院颁布的需要特殊管理的28种毒麻中药品种之一。临床应用广泛，疗效确切。《部颁标准》和《中国药典》88个成药制剂（329个批号）均含有之。目前商品蟾酥质量问题突出，混伪、掺假现象普遍存在。构建蟾酥科学完善的质量控制方法，既能保障临床用药安全有效，也可为探讨动物药质量控制研究提供示范。因此，本项目在“Totality-of-the-evidence”（简称TOE）思路指导下，针对蟾酥质量控制方法及影响品质的关键因素（基原动物的鲜浆品质及其加工方式）开展深入研究。具体内容：选择蟾酥主流品种，融合化学和蛋白组学技术，以不同来源蟾酥的差异性生物标志物（差异蛋白或特征多肽，蟾蜍甾或吲哚生物碱）为主线，在传统功效相关模型评价的基础上，建立整合的质量控制方法，规范其生产加工过程，促进药材品质提升。

动物药是中医药临床应用的三大组成之一，其质量控制技术水平亟待提高。蟾酥为我国贵重动物药品种，也是国务院颁布的需要特殊管理的28种毒麻中药品种之一。临床应用广泛，疗效确切。《部颁标准》和《中国药典》88个成药制剂（329个批号）均含有之。目前商品蟾酥质量问题突出，混伪、掺假现象普遍存在。构建蟾酥科学完善的质量控制方法，既能保障临床用药安全有效，也可为探讨动物药质量控制研究提供示范。因此，本项目在“Totality-of-the-evidence”（简称TOE）思路指导下，针对蟾酥质量控制方法及影响品质的关键因素（基原动物的鲜浆品质及其加工方式）开展深入研究。具体研究内容如下：首先总结了动物药整体质量研究现状、蟾酥药用品种及传统优良品质特征等方面的研究进展；采集和收集主产地蟾酥样品和市售样品57批；构建了蟾酥中蟾蜍甾、吲哚生物碱、蛋白的定性、定量分析方法，并对不同来源的蟾酥样品进行了小分子成分和蛋白多肽类的比较分析；采用体内外药理模型评价了蟾酥总提物、类成分群的抗炎镇痛作用以及急性毒性；起草了蟾酥商品规格等级标准以及蟾酥药材和饮片蟾酥粉的质量标准，并将药材的一测多评法拓展用于蟾酥制剂的质量控制，建立了基于近红外光谱技术的高品质蟾酥快速检测方法。研究结果对于规范蟾酥的加工过程，提升药材品质，推动蟾酥药材及其制剂产业的健康有序发展具有重要意义。同时，本研究为动物药整体质量控制水平的提升探索了可借鉴的思路和方法。