芪麝丸治疗颈椎病四种关联中医体质人群群体药代动力学研究

Qishe Pill, as a compound preparation of traditional Chinese medicine, has been used for more than ten years. It has obvious therapeutic effect on the treatment of Qi defieieney and blood stasis syndrome in nerve root type cervieal spondylosis, but its guidance of clinical application is not detailed enough, and it also has no corresponding medication guidance methods for certain specific crowd symptoms. This project, which based on combination of "Quantitative Pharmacology" method and "constitutions of TCM" ideology these two disciplines, studies and analyses the population pharmacokinetic parameters and models of absorption, distribution, metabolism and excretion in total four process of Qishe Pill's components, in relationship with age, sex, BMI index, habits, occupation and four kinds of traditional Chinese medicine constitution type, which consist of Qi deficiency, blood stasis, both of Qi deficiency and blood stasis , Yin-Yang harmony. It explores the corresponding relationship and mechanism of interaction of Qishe pill’s components’ disposal process in healthy human body and traditional Chinese medicine constitutions. It is important to elucidate the interaction between the Qi deficiency and blood stasis’ effects on disposal process of Qishe pill components in vivo. In addition, it can show more accurate and objective clinical evidence for the further research, application and promotion of the constitution types of traditional Chinese medicine. It also can provide a theoretical basis for Qishe pill in the monitoring clinical treatment of cervical spondylosis, defining applicable scope and individual treatment ideas.

芪麝丸是已应用十余年的中药复方制剂，对治疗气虚血瘀神经根型颈椎病有显著治疗效果，但其临床应用的指导还不够深入细化，针对某些特定人群出现的不适症状也还没有对应的用药指导方法。结合“定量药理学”技术手段和“中医体质学”分型思想，本项目从芪麝丸各成分及主要代谢产物在人体中的吸收、分布、代谢和排泄过程群体药代动力学的研究出发，定量分析该药体内过程与中医体质四种分型（单纯气虚质、单纯血瘀质、气虚血瘀复合质和平和质）以及年龄、性别、BMI指数、习惯嗜好、职业等个体特征因素的关系，探讨芪麝丸在人体内的过程与中医体质等个体特征因素的相应关系及相互作用机制，明确气虚质和血瘀质两种体质之间的交互作用，还可为中医体质分型提供更准确客观的临床证据，为芪麝丸治疗颈椎病的临床治疗监测、中医适用范围界定和临床个体化治疗思路提供理论指导参考依据。

芪麝丸是新一代治疗颈椎病的中药复方制剂，具有益气化瘀、祛风通络、舒筋止痛之功效，主要适用于气虚血瘀证神经根型颈椎病。本研究从“定量药理学”和“中医体质学”两个学科的结合出发，对气虚质、血瘀质、气虚血瘀复合质和平和质这四种中医体质分型下芪麝丸各成分在人体药代动力学参数及模型的关系加以研究和分析，探索芪麝丸在健康人体内的过程与中医体质间的相应关系及相互作用机制。本研究运用HPLC技术建立芪麝丸的指纹谱质量控制方法，建立标准指纹图谱，并对多批次的制剂进行质量均一性评价分析，发现不同批次间芪麝丸指纹图谱差异性很小。收集了38位志愿者的血浆样品，并建立了芪麝丸中两种指标性成分青藤碱、木兰花碱人体血浆中浓度的UPLC-MS/MS测定分析方法，运用Kinetica 5.0 药代动力学软件拟合药代动力学参数，采用SPSS 18.0统计学软件方差分析法对各中医体质分型组别的两成分主要药动学参数进行组间多重比较，用以研究健康受试者口服芪麝丸后两种成分的体内药代动力学特征与中医体质分型的关系。方法学验证结果表明该测定分析人体血浆中两种成分的方法灵敏度高、专属性好、稳定可靠、分析时间短。组间差异性统计分析结果显示不同体质组间的青藤碱药代动力学参数没有显著性差异，而木兰花碱某些药动学参数（如Cmax和AUC等）却存在差异性（P<0.05）。表明四种中医体质分型可能不是影响青藤碱在体内处置过程个体差异的关键因素，却对木兰花碱的体内处置过程有明显影响。由于木兰花碱体内暴露量较小，具体个体化给药方案还有待于进一步研究。