现代生物技术与中医药

单击此处编辑母版标题样式,编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,大家好,现代生物技术与中医药,（研究生课程）,高川,PH.D,湖北中医药大学检验学院,电话,QQ: 8608888,12/8/2016,2,第一、二节课,中西医学发展史。,中西医内容都是基于实践经验总结，是客观。,近现代多种因素导致了中西认知技术和理念发展差异，使得中医与西医差异愈来愈大。,3,4,当代中西医在世界范围内交叉共存,中国：“中西医结合”。,西方：,针灸在主要西方国家被接受和推广。,传统针灸、电针、光针、,针灸师之外中医人员不能以医生身份执业,中药材、方剂能作为辅食售卖。,Dietary Supplement Health and Education Act,（,1994,）。,NIH,在,1992,年就建立了,Office of Alternative Medicine.,西方在制度上给中医药留了后门！,5,The Terminal (2004),许充不许赖,!,6,癌症是威胁人类健康最大杀手之一,治疗癌症主要手段：,手术。,放疗、化疗。,靶向疗法。,“靶向”疗法选择很有限。,非靶向疗法副作用较大。,7,癌症治疗常伴随着副作用：,疲倦、痛：头、肌肉、胃部、指趾端。,口、喉咙干涩。,腹泻。,眩晕、呕吐。,便秘。,血液问题。,神经系统问题。,思维、记忆。,性功能、生育功能。,胃口降低。,脱发。,药物常常不得不减量,或者间歇给药。,8,9,中医药在西方传播：润物细无声,美国截止,2003,年统计：,4,0%-70%,癌症病人在接受西医治疗同时使用了中医药。,典型病人均受过良好教育，约,30-50,岁，居住在西部和东北部。,73%,病人使用中医药后对治疗结果更为乐观。,4,8.9%,病人相信中医药比西医药危害小。,4,3.8%,病人希望更多参与治疗计划制定。,病人对使用中医药期待：,提高生活质量（,76.7%,）。,刺激免疫系统（,71.1%,）。,延长存活期（,62.5,）。,减小症状（,47%,）。,根治疾病（,33%,）。,10,中医药在西方传播：润物细无声,2001,年，美国癌症病人在中医药方面共花费约,211,亿美元。,看“中医”频率超过了看家庭医生。,中草药使用非常频繁。,由于法律不要求对中医药产品鉴定和药理研究，因此他们效果缺乏科研和临床数据支持。,复方使用使中医药难于标准化。,11,缺乏客观统一标准影响中医药推广,粉防己,（,Stephania tetrandra,）,广防己,（,Aristolochia fangchi,）,1,993,年，比利时有,1,00,多人使用了同一诊所提供中医减肥药物后出现了严重肾病和癌症。追根溯源，发现是配药时候把广防己（含马兜铃酸）错当成了粉防己。,中医标准化亟待解决！,12,现代生物技术研究中药,检测技术。,体外试验：,分子生物学、细胞生物学、生物化学。,动物实验：,模式生物、疾病模型。,临床试验：,I,、,II,、,III,期。,推广上市、后期跟进。,13,现代西药开发,公共卫生、临床数据找寻目标疾病。,找寻药物靶点。,开发候选药物。,筛选、修饰。,临床前验证。,临床上验证。,上市。,14,找寻目标基因：临床大数据统计,doi:10.1038/nm.3247,15,找目标目标基因：组学分析,doi:10.1038/nm.3247,16,候选目标：细胞增殖分析,17,候选目标：细胞增殖凋亡周期分析,18,候选目标：细胞迁移分析,19,候选目标：克隆形成分析,20,建立动物模型,21,荷瘤小鼠,22,荷瘤小鼠数据采集,23,现代西药开发,公共卫生、临床数据找寻目标疾病。,找寻药物靶点。,开发候选药物。,筛选、修饰。,临床前验证。,临床上验证。,上市。,24,现代西药开发,公共卫生、临床数据找寻目标疾病。,找寻药物靶点。,开发候选药物。,筛选、修饰。,临床前验证。,临床上验证。,上市。,挖掘现成中药验方！,25,郑永齐,26,27,“新”中药复方：,PHY906,源自黄芩汤。,始于约,1800,年前。,用于消化道病恙治疗：腹泻、恶心、呕吐、,复方：,标准化：,精简配方。,建立质控流程。,28,PHY906,PHY906 is spray-dried aqua extract of four medicinal herbs,Huangqin(dried roots of Scutellaria baicalensis Georgi),Baishao (driedroots of Paeonia lactiflora Pall),Gancao (dried and honey-fried roots and rhizomes of Glycyrrhiza uralensis Fisch, G. inflata Bat, or G. glabra L.),Dazao (dried fruits of Ziziphus jujuba Mill).,provided by PhytoCeutica Inc (New Haven, CT, USA), raw material provided by Sunten Inc. (Taiwan),29,PMID:,18648130,30,31,胰腺癌、卡培他宾,肝癌、索拉非尼,晚期直肠癌,极晚期肝癌、卡培他宾,局部晚期直肠癌,、卡培他宾,转移直肠癌,、伊立替康,32,LS/MS,质控,根据已知组份引入标准品作参照。,Paeoniflorin, baicalin, baicalein, wogonin, scutellarin, and glycyrrhizic acid were from the China Institute for Control of Pharmaceutical and Biological Products (Beijing, China).,Chrysin,，,gallic acid,，,HPLC-grade acetonitrile (MeCN) were from Sigma-Aldrich (St Louis, MO,USA).,LC/MS-grade water containing 0.05% formic acid (v/v) was from J.T. Baker (Phillipsburg, NJ, USA).,33,LS/MS,质控,制样,HPLC,MS,34,()-ESI total ion current of PHY906 and the four individual herbs. S1/4Scutellaria baicalensis, P1/4Paeonia lactiflora, G1/4Glycyrrhiza uralensis, Z1/4Ziziphus jujuba.,35,36,组份鉴定,Compounds identified in PHY906 by LC/MS,37,38,代谢组份鉴定,PhytomicsQC,39,Figure 6 Schematic for gene expression bioresponse fingerprint,40,PMID:,18648130,41,42,减组份分析,43,关于引导写作（,guided journal,）,关键词。,关键人。,44,关于引导写作（,guided journal,）,关键词。,关键人。,45,46,47,48,Results: Eighteen batch samples of Huangqin Tang (HQT) and its pharmaceutical grade version (PHY906) were,analyzed using the PhytomicsQC platform analysis. Comparative analysis of the batch samples with a clinically,tested standardized batch obtained values of PSI similarity between 0.67 and 0.99.,Conclusion: With rigorous quality control using analytically sensitive and comprehensive chemical and biological,fingerprinting, botanical formulations manufactured under standardized manufacturing protocols can produce,highly consistent batches of products.,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,Bioactive constituents in the Chinese medicine formulation PHY906 were analyzed by a newly established LC/MS method. A total of 64 compounds were identified or tentatively characterized based on their mass spectra determined in both negative and positive ion modes. Further structural information was obtained from in-source fragmentation. The compounds identified included flavonoids, triterpene saponins, and monoterpene glycosides. All of them were also detected in the corresponding individual herbs. Some of these compounds had been reported from the herbs, while the others are reported for the first time. Thus, the majority of the chemical compounds in PHY906 were specifically clarified from the qualitative perspective. The LC/MS method established in this study could also be used for quality control of PHY906, and may facilitate the identification of in vivo metabolites of this complex formulation. Quantitative analysis of major bioactive compounds in PHY906 is still underway in our laboratory.,77,