急性高原病(AHAD)多发于急进高原人群,轻者出现头痛、恶心等反应,重者可危及生命.早期预测和筛查AHAD的高风险人群,对减少AHAD的发生意义重大.当前的研究主要是通过对易感人群、易感模式、易感因素和易感指标等的分析,对AHAD进行预测,促进了AHAD发病人群的早期筛查,但其准确性和效率亟待提高.中医在"治未病"理念的指导下,结合病因、病机及体质学说,基于"望闻问切"四诊信息,通过辨别易感人群的体质偏颇,观察证候分布及演变规律,确定中医风险因素,建立具有中医学特色的AHAD预测体系,以期弥补当前对AHAD预测的不足,提高AHAD的预测效率和准确性.

Introduces the regulatory requirements of the Natural and Over-the-Counter Health Products Administration on the quality of natural health products, and adopts the literature research method to translate and interpret Health Canada's "Guidelines for the Quality of Natural Health Products" on the quality management and quality control of natural health products. Policy documents, from the perspective of stakeholders, provide requirements for the detection methods and standards of natural health products, such as characterization, identification experiments, component content, pollutants and impurity content detection, etc. To achieve natural health Quality management and quality control in the whole process of product production. Familiar with and understand the requirements for the quality management of natural health products in Canada will help to promote the legal and compliant management of product quality in the production process of Traditional Chinese Medicine (TCM) products after registration in Canada, and promote the production and sustainable development of TCM products. At the same time, it provides a reference for further improving my country's drug quality management system normative system documents, and assists the effective connection between the registration-related standards of Chinese patent medicines and international standards.

中药产品属于加拿大传统药物的范畴,可以通过传统药物声明的申请途径取得加拿大天然健康产品许可证.构建资质证据材料体系,从传统药物申请途径的适用性、传统药物的安全性和有效性 3 个方面评价药品,并提出一种证据评估模板,帮助申请人准备符合标准的证据,推动中药国际化注册进展,为我国完善药品注册体系提供参考.

At present, the registration process of Traditional Chinese Medicine (TCM) in Canada is refering to the requirements of Natural Health Products (NHPs). In terms of registration material, both NHPs and TCM include plants, animals and minerals with medicinal components, but the fundamental difference between them is that TCM is guided by the basic theory of TCM. As for the registration classification of TCM in Canada, first of all, judge whether the product to be applied for is NHPs; Secondly, we should clarify the types and ways of registration, mainly including simple application, traditional application and non-traditional application, and provide application forms, label texts, summary reports, evidence, animal tissue forms, finished product specifications and other materials according to different requirements. At present, the successful registration experience of TCM products in Canada mainly mainly includes applying for superior varieties, selecting appropriate application channels, communicating with local health management units and providing sufficient scientific evidence and good clinical application records. The regulations on the registration of NHPs in Canada have not fully considered the particularity of TCM and the registration of TCM products is still facing some difficulties. In the future, we can learn from the registration process and requirements of the Health Canada, promote the interconnection and mutual recognition of the Pharmacopoeia of the People's Republic of China and the NNHPD monographs in Canada, reduce the obstacles to the local application for registration of TCM, and promote the further improvement of the international standards of TCM.

This paper analyzes the laws, regulations and concre measures of Traditional Chinese Medicine (TCM) in Canada, so as to provide reference for TCM products to enter Canada, and for the establishment of TCM regulation system and the improvement of its detailed rules in China. The regulation of TCM in Canadian, on the one hand, supervision is to provide guidance for the protection of consumers' rights and interests, including the guidance of rational drug use and rational purchase for consumers; on the other hand, it is to supervise enterprises, including the safety, effectiveness and quality certification of TCM products, labeling and packaging requirements, as well as the site certification of product manufacturing, packaging, labeling and import. The Ministry of health of Canada takes evidence as the core of evaluation, and ensures the safe and effective use of TCM products in Canada through product and site licensing evaluation. In the supervision of TCM, relevant departments in China should further strengthen the protection of consumers' drug rights and interests, strengthen the construction of TCM registration evidence system, and pay attention to the risk management of drug production quality.

目的:探讨热炎宁合剂(RYN)联合利奈唑胺(LNZ)对耐甲氧西林金黄色葡萄球菌(MRSA)及其生物膜的抑制作用.方法:采用微量稀释法测定RYN和LNZ对MRSA的最低抑菌浓度(MIC);微孔板法检测在生物膜生长过程中4个时间点(0,6,12,24 h)的MRSA给药前后活菌量的变化;扫描电镜观察24 h时MRSA形态学变化;细胞代谢组学技术检测在4个时间点时两药联合干预MRSA的内源性小分子终端代谢物的变化.结果:RYN和LNZ的MIC分别为1/2原液和4mg·L-1.单用LNZ(2 mg·L-1)0h活菌量抑制效果优于1/16 RYN单用,6,12,24 h则单用1/16 RYN优于单用LNZ.RYN联合LNZ在4个时间点的抑制作用均优于单用组.两药联用对24 h时MRSA生物膜形态学结构的破坏优于单用组.环磷酸腺苷(cAMP),二磷酸腺苷(ADP)-D-核糖和2-甲基丁酰辅酶A(2M-CoA)是与被膜形成相关的代谢物;LNZ对这3个代谢物无治疗作用,RYN在12,24 h分别对2M-CoA和ADP-D-核糖产生影响;两药联用在24 h对三者均有治疗作用.L-色氨酸、苯丙酮酸、胞苷和癸二酸是LNZ的药效代谢标志,相关的生物通路有苯丙氨酸、酪氨酸和色氨酸的生物合成,苯丙氨酸代谢.L-组氨酸,尿酸,L-赖氨酸等4个代谢物是RYN的药效标志,相关的生物通路有苯丙氨酸代谢和氨酰转移核糖核酸的生物合成.L-色氨酸,L-赖氨酸,鞘氨醇-1-磷酸等9个代谢物与两药联用的药效相关,相关的生物通路有氨酰转移核糖核酸的生物合成,苯丙氨酸、酪氨酸和色氨酸的生物合成,新生霉素生物合成和酪氨酸代谢.结论:RYN联合LNZ干预MRSA在其生物膜生长的各时间点均有抑菌增效作用;抑制被膜的机制与cAMP代谢相关;两药联合增效作用则与氨酰转移核糖核酸的生物合成,苯丙氨酸、酪氨酸和色氨酸的生物合成相关.RYN与LNZ联用可作为临床治疗MRSA感染的潜在有效方案.