中药现代化与国际化探索 - 图文 

Engineering5(2019)1–2Contents lists available at ScienceDirectEngineeringEditorial

TheQuestfortheModernizationandInternationalizationofTraditionalChineseMedicine

BoliZhanga,ShengliYangb,De-anGuocaTianjinUniversityofTraditionalChineseMedicine,Tianjin300193,ChinaShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,Shanghai200031,ChinacShanghaiInstituteofMateriaMedica,ChineseAcademyofSciences,Shanghai201203,ChinabTraditionalChinesemedicine(TCM)isdeeplyrootedinancientChinesecultureandhasbeenpracticedbyChinesepeopleforthousandsofyearsinordertomaintaintheirhealthand?ghtagainstdisease.ThisancientChinesewisdomhasaccumulatedfromthelongstruggletocopewithvariousdiseasesthroughhundredsoreventhousandsoftrial-and-errorpractices.However,duetoitsempiricalcharacter,TCMhaslongbeencriticizedasbeingde?cientinscienti?cevidence,andisstillnotwidelyacceptedbythemainstreamconventionalmedicalsystem.ThecomplexityofthechemicalcomponentsofTCMandtheclari?ca-tionofitsmechanismsremainanenormouschallengeinthecon-versionofTCMintoanevidence-basedmedicine.Thankstoincredibleprogressinbiomedicalresearch,TCMhasevolvedatanastonishingpaceinvariousaspects,asindicatedbythe2015NobelPrizeawardedtoProfessorYouyouTuforherdiscoveryofartemisinin.In1996,theChinesegovernmentlaunchedtheActionPlanforModernizedScienceandTechnologyIndustryofTCM(hereinafterTCMModernizationPlan),whichwasaimedatendowingTCMwithamplescienti?cevidenceintermsofitssafety,ef?cacy,quality,modesofaction,mechanisms,andsoforth.After20yearsofarduousexploration,dramaticprogresshasbeenachievedinChineseherbalcultivation,TCMchemistry,TCMpharmacology,processing,qualitycontrol,safety,ef?cacyvalidation,goodmanu-facturingpractice(GMP)manufacturing,theTCMpharmaceuticalindustry,andmore.Sincetheimplementationofgoodagriculturalpractice(GAP)inChinesemateriamedicain2002,over100commonlyusedChineseherbshavebeencultivatedbystandardoperatingprocedure(SOP)inaccordancewithGAPrequirements;theseherbsincludeSalviamiltiorrhiza,Astragalusmembranaceus,Panaxnotoginseng,Glycyrrhizauralensis,Isatistinctoria,andmanymore.ResearchonTCMchemistryandphytochemicalanalysishasreachednewheightsaswell,withmorethan6000newnaturalproductshavingbeenisolatedandcharacterizedfromTCMherbs,includingagreatnumberofbioactivecompoundswithpotentialfordevelopmentintonewdrugs.Withtherapiddevelopmentofhyphenatedtechnologies,thenumberofcomponentscharacter-izedinasingleherbthroughsheerphytochemicalanalysisisgrow-ingbygeometricprogressionintothehundredsoreventhousands,whichgreatlyfacilitatestheelaborationofTCMqualitystandards.TheparadigmofTCMqualitycontrolhasshiftedfromasingle-markermodeltoaholisticapproachwith?ngerprintpro?lingandmulticomponentassaysastheprominentfeatures,inordertoenabletheevaluationofbatch-to-batchconsistencyandoverallquality.TCMglobalizationhasalsoprogressedinanunprece-dentedmanner,withnine?nishedTCMproductscurrentlyinphaseIIorphaseIIIclinicaltrialsforUSFoodandDrugAdministra-tion(FDA)registration.Over15qualitystandardsofChineseherbshavebeenadoptedintheUnitedStatesPharmacopeiaand75TCMqualitymonographshavebeenrecordedintheEuropeanPharmacopoeia.ThegrossvalueoftheindustrialoutputofTCMhasreachedanewhighofover800billionCNY(about118billionUSD),whichis20timesgreaterthanthevaluein1996,thestartingyearofthenationalTCMModernizationPlan.Tore?ectrecentprogressanddevelopmentinTCMresearchandtooutlinefutureperspectivesinthis?eld,wehaveorganizedthisspecialissuededicatedtoTCMmodernizationandinternation-alization.Fourteenarticles,coveringanarrayofresearchdirec-tions,wereinvitedfromprominentscholarsandresearchersinthe?eld.Majorityofthesearticlesarenowpublishedinthisissue,thefollowingwillbepublishedinthefutureissues.Inthisspecialissue,YouyouTuandhercolleaguesreviewthepast,present,andfutureofartemisinin.Theantimalarialmechanismofartemisinin,thechallengeto?ghtagainstemergingartemisinin-resistantmalaria,andthepotentialuseofartemisinintotreatdiseasesotherthanmalaria,suchascancerandlupuserythematosus,are2B.Zhangetal./Engineering5(2019)1–2discussedinthisreview.ProfessorLan-JuanLiandhercolleaguesdiscussnewandincreasingevidenceoftherelationbetweengutmicrobiotaandhosthealth,whichmaybeassociatedwiththetherapeuticactivityofTCMformulas.ThecorrelationbetweenTCManddiseasessuchaschronicliverdisease,ulcerativecolitis,obesity,andtype2diabetesishighlighted,andfutureresearchisenvisioned,rangingfromexperimentaldesigntothedisclosureofinteractionsbetweenTCMsandthegutmicrobiota.Anewconceptforqualitycontrolnamedthe‘‘qualitymarker”isproposedbyProfessorChangxiaoLiuandhiscolleagues,andisappliedinanumberofcasestudies.Theprincipleofthisnewconceptandapproachestopracticeitareexpoundedindepth.InordertoelucidatetheactionmechanismofcomplexTCMsystems,thetermchinmedomicsisde?nedbyProfessorXijunWangandhiscolleaguesinthearticleentitled‘‘Chinmedomics:Apowerfulapproachintegratingmetabolomicswithserumpharmacochem-istrytoevaluatetheef?cacyoftraditionalChinesemedicine.”Dr.WernerKnoess,theformerchairmanoftheCommitteeonHerbalMedicinalProducts(HMPC)oftheEuropeanMedicinesAgency,describesthedetailedrequirementsfortheregistrationofTCMproductsintheEuropeanUnion,whichservesasguidanceforChineseenterprisesthatmaybeinterestedinfollowingthisprocess.Safetyandqualityissuesarealsoemphasizedintwopapersthatfocusonsummarizingtheprosandconsofthesetwoimportantfactorsofmedicineasawhole.OtheraspectsofTCMresearcharecoveredintheremainingpapers,whichinclude:TCMtreatmentforrheumatoidarthritis;ananalysisofSalviamedicinalplantsgenomes;aDNAmolecularmarkertodifferenti-atebetweenplantspecies;micro-andnano-formulationtoimproveTCMbioavailability,tissuedistribution,andef?cacy;andanelectro-acupuncturemulticenterrandomizedcontrolledclinicaltrial,whichclearlyshowsthemovementofTCMtowardbecominganevidence-basedmedicine.ThemodernizationandinternationalizationofTCMisaprocessthatwilltakeaconsiderablelengthoftime;itrequirestheadoptionofnewtechnologiesindiversescienti?c?eldsandclosecooperationamongscholarsinmultipledisciplines.InthequesttodecipherthemythsofTCMtheoryandactionmechanisms,allpossibleresourcesmustbeallocatedinordertorealizethisgoal,whichwillbene?tthehealthofallhumankind.Engineering 2 (2016) xxx–xxxContents lists available at ScienceDirect

Engineering

Editorial中药现代化与国际化探索张伯礼a，杨胜利 b，果德安 cab Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, Chinac Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China管理规范（GAP）实施以来，根据中药材生产质量管理规范要求通过标准操作规程（SOP）栽培了超过100种常用中草药，其中包括丹参（Salvia miltiorrhiza,）、黄芪（Astragalus membranaceus）、三七（Panax notogin-seng）、甘草（Glycyrrhiza uralensis）、菘蓝（Isatis tinc-toria）等。中药化学与植物化学分析方面的研究也达到新高度，从中草药中分离和鉴定了6000多种新的天然产物，包括可能用于新药开发的大量生物活性化合物。随中药深深扎根于中国古代文化，几千年以来，为了保持健康并对抗疾病，中国人民不断进行着中药实践。这种古老的中国智慧是通过经历成百甚至上千次反复试验的长期斗争积累起来的。然而，由于其基于经验的特点，中药一直以来被诟病为缺乏科学依据，至今仍未得到主流传统医学体系的广泛认可。中药化学成分的复杂性及其机制的阐明仍是将中医学转化为循证医学的巨大挑战。生物医学研究方面取得的巨大进展使中药在各方面均取得了惊人的发展，2015年屠呦呦教授因发现青蒿素而被授予诺贝尔奖就是一个例证。1996年，中国政府启动《中药现代化科技产业行动计划》（以下简称《中药现代化计划》），旨在使中药具备安全性、药效、质量、作用方式、机制等方面的科学依据。经过20年的艰苦探索，我国在中草药栽培、中药化学、中药药理学、加工、质量控制、安全性、药效验证、药品生产质量管理规范（GMP）生产以及中药制药业等方面取得了巨大进步。自2002年中药材生产质量着联用技术的快速发展，通过单纯植物化学分析而被鉴定为同一种草本植物成分的数量正以几何数量级不断增长至数百甚至数千种，极大地促进了中药质量标准的制定。中药质量控制模式已从单标记模式转变为以指纹图谱和多组分分析为主要特征的整体研究，以便评价各批次一致性和整体质量。中药全球化也取得了前所未有的进展，目前有9种申报美国食品和药物管理局（FDA）注册的中药成品正处于第二阶段或第三阶段临床试验。《美国药典》中采用了15种以上中草药质量标准，而《欧洲药典》收录75种中药质量专论。中药产业总产值创造新高，超过8×1011元人民币（约1.18×1011 美元），比 1996年启动《国家中药现代化计划》当年的总产值高20倍。为了反映中药研究的最新进展和发展并概述本领域的未来前景，我们组织了本次中医药国际化专题，专门讨论中药现代化和国际化。涵盖一系列研究方向的14篇论文均来自本领域的杰出学者和研究者。其中，大多数2Author name et al. / Engineering 2(2016) xxx–xxx论文现于本期发表，其余论文也将在未来的各期发表。在本期专题中，屠呦呦教授及其同事分别论述了青蒿素的过去、现在及未来。该篇综述讨论了青蒿素的抗疟机制、对抗新型青蒿素抗药性疟疾的挑战以及青蒿素治疗疟疾之外的其他疾病（如癌症与红斑狼疮）的潜在用途。李兰娟教授及其同事探讨了新的、不断增长的证明肠道菌群和宿主健康之间联系的证据，指出其可能与中药方剂的治疗活性相关。文中强调了中药与慢性肝病、溃疡性结肠炎、肥胖症以及2型糖尿病等疾病之间的相互关系，并表示将进行更多的研究，涉及实验设计、揭露中药与肠道菌群间的相互作用等。“质量标记物”这一质量控制新概念由刘昌孝教授及其同事提出，并运用于大量的病例研究中，文中对这一新概念的原理和实践方法进行了深入的阐述。为了阐明复杂的中药体系的作用机制，王喜军教授及其同事在《中医方证代谢组学——中药效应评价的有效途径》一文中定义了“中医方证代谢组学”一词。欧洲药品管理局草药产品委员会（HMPC）前主席Werner Knoss博士描述了在欧盟注册中药产品的详细要求，这对可能有兴趣遵照这一过程进入欧洲市场的中国企业起到指导作用。有两篇论文总体上着重总结了医学中两个重要因素（安全性和质量）的利弊，也强调了安全性和质量问题。其余论文也涵盖了中药研究的其他方面，包括：类风湿性关节炎的中药治疗，丹参药用植物基因组分析，区分植物种类的DNA分子标记，改善中药生物利用度、组织分布及疗效的微纳米制剂以及电针多中心随机对照临床试验，后者清楚地表明了中药向循证医学发展的趋势。中医药现代化与国际化是一个历时相当长的过程，需要采取多种科学领域中的新技术，也需要多学科间的学者紧密合作。为了探索中药理论与作用机制方面的神秘之处，必须分配一切可能的资源，这将有利于全人类的健康。