版权说明:本文档由用户提供并上传,收益归属内容提供方,若内容存在侵权,请进行举报或认领
文档简介
UnitoneTxtADevelopmentofnewdrugs新药研发医学知识培训第1页Newwordsandexpressionacute:acuteinfection(急性感染),acuteleukemia(急性白血病)chronic:chronicgastritis(慢性胃炎)agonist:stimulatorantagonist:blockeradversereaction(不良反应):anybadeffectorundesirableeffectcausedbydruguseatnormaldose(正常剂量)新药研发医学知识培训第2页newchemicalentity(新化学实体):newcompoundshowspharmacologicalactivityagainstcertaindisease,whichisalsocalledleadcompound(先导化合物)ordrugcandidate(候选药品)in-vitro(体外):outsideoforganismsinvivo(体内):withinawholelivingorganism新药研发医学知识培训第3页1.Whatisanewdrug?Chemicalstructure(化学成份)
Dosageform(剂型)Routeofadministration(给药路径)Indication(适应症)Newdrug新药研发医学知识培训第4页2.Whydoweneednewdrugs?manyincurablediseasesstillawaitconquesttoproducenewdrugsthataresuperiorthanexistingmedicationstheultimategoal:toprovideeffective,accessibleandaffordablemedicinesforall新药研发医学知识培训第5页①Inthepast,drugswereextractedfromplantandanimalsources,butthepurityofdrugswasverylimited.quinine(奎宁):extractedfromthebarkofcinchona(金鸡纳树皮),itsantimalarial(抗疟疾)functionwasdiscoveredbytheIndiansinNorthAmerica
3.Evolutionofnewdrug新药研发医学知识培训第6页②From1900chemicallysynthesizeddrugsbecameavailable,thepurityofdrugswereremarkablypromotedwhichincreasedthespecificityofaction.e.g.quininecanbeartificiallysynthesizedin1945Nowadaysmostwesternmedicinesaretotallysynthesizedorsemi-synthesized新药研发医学知识培训第7页③Withthedevelopmentofgeneticengineering(基因工程)moredrugswillbeproducedartificially.
e.g.thefirstgeneticallyengineereddrugisrh-insulin(forthetreatmentofdiabetes)andwasfirstmarketedinAmericain1982.新药研发医学知识培训第8页4.RegulationofdrugdevelopmentTherangeofnovelchemicalentitiesdevelopedhasoccasionallyledtounexpectedtoxicity.Inordertoensurethesafetyandefficacyofnewdrugs,theirdevelopmentmustfollowstatutoryprocedures(法定程序).新药研发医学知识培训第9页
Thalidomide--------abigtragedy!
ThalidomidewasdevelopedbyaGermanpharmaceuticalcompany.Itwassoldfrom1957to1961inalmost50countriesunderatleast40brandnames.Thalidomidewaschieflysoldandprescribedtopregnantwomen,asanantiemetic(止吐药)tocombatmorningsicknessandasanaidtohelpthemsleep。In1961whenthalidomidewaswithdrawnfromthemarket,morethantenthousanddeformedbabieswereborn.Theysufferedfromphocomelia(海豹肢).
新药研发医学知识培训第10页
Developinganewdrugisahighlycomplex,time-consuming,riskyandcostlyprocess.5.Anoverviewofnewdrugdevelopment新药研发医学知识培训第11页complexandtime-consumingNewdrugdevelopmentrequiresmultidisciplinaryeffortsformanyyears,involvingnumerousstepsandmanysophisticatedtechniques0.5-1year3-4years6-8years2-3years新药研发医学知识培训第12页risky:
OnlyaverysmallportionofNCEscanbefinallymarketedasdrugproduct新药研发医学知识培训第13页costly:
Onebillion新药研发医学知识培训第14页6.Developmentofnewdrugs6.1Strategiesfordiscoveringnewchemicalentities①Serendipity:Thenewtherapeuticagentisdiscoveredbychance.e.g.thediscoveryofpenicillin
AlexanderFleming
penicillum新药研发医学知识培训第15页②Molecularroulette(分子轮盘赌)Agreatmanyofnewchemicalstructuresweresynthesizedrandomlyandscreenedbyanimalorin-vitromodelsofhumandiseasetoseeifanyofthenewlyobtainedstructuresprovecertaineffect.Disadvantage:wasteful,dependentonsensitivemodelsforscreening新药研发医学知识培训第16页③Minorstructurechangesinexistingagents
Penicillin,青霉素Penicillin∨Oxacillin,苯唑西林Ampicillin,氨苄西林新药研发医学知识培训第17页Disadvantagesofpenicillin:unstabletoacidunstabletoβ-lactamase(内酰胺酶)littleeffectonGramnegativebacteria(革兰氏阴性菌)新药研发医学知识培训第18页
④Programmedbasicresearchwithsynthesisofspecificchemicalse.g.1Histamie(H2)receptorantagonist(suchasCimetidine西米替丁)forpepticulcerHistaminereceptorscanbeclassifiedintothreeclasses,H1,H2andH3,theydistributeindifferenttissues,andcausedifferenteffectswhenagitated.H2receptorexistsingastricwallcells,whenagitatedbyhistaminethesecretionofgastricacidisenhanced,causingpepticulcer.H2receptorantagonistcanspecificallybindwithH2receptorbutwithoutagitation.
新药研发医学知识培训第19页
e.g.2angiotensin-convertingenzymeinhibitor(血管担心素转化酶抑制剂)forhypertensionangiotensinⅠisconvertedtoangiotensinⅡbyangiotensin-convertingenzyme.angiotensinⅡcanbindwithangiotensinreceptor(AT,existinginvascularsmoothmuscle),leadingtovasoconstrictionandriseofbloodpressure.angiotensin-convertingenzymeinhibitorsuchasCaptopril(卡托普利)canbindwiththeconvertingenzymes,thusangiotensinⅠcouldn'tbindtotheconvertingenzymesandwon’tbeconvertedtoangiotensinⅡ.新药研发医学知识培训第20页⑤ClinicalobservationofdrugactioninpracticeNewpharmacologicalactionwhichisnotdetectedinanimalmodelsmaybediscoveredinclinicalapplication.thiazidediuretics(噻嗪类利尿剂)areusedforthetreatmentofedema(水肿),theirantihypertensiveeffectswasnotpredictedfromanimalscreeningtest,butidentifiedafterthedrugsweremarketedandbeingusedinpractice.新药研发医学知识培训第21页6.2Pre-clinicalstudies
①medicinalchemistrystudies:technologyforproduction,chemicalandphysicalproperties,stability,dosageform,standardsforqualitycontrol
新药研发医学知识培训第22页②pharmacologicalandtoxicologicalstudiesinclude:pharmacodynamic(药品效应动力学)studies:drugaction(therapeuticeffectandadverseeffect)dose-effectrelationship(minimaleffectivedose,maximaleffect,medianeffectivedose,medianlethaldose)mechanismofaction(作用机制):interactionwithitstargetpharmacokinetic(药品代谢动力学)studies:absorption,distribution,metabolismandexcretionofthedrugtoxicityinanimals:acutetoxicity,chronictoxicityspecialtoxicity新药研发医学知识培训第23页SomeimportantdefinitionsintoxicologicalassessmentAcutetoxicitytesting:acutetoxicreactionswithin24hoursaftersingledosingChronictoxicitytesting:toxicreactionswhichresultfromrepeateddoses,usuallyforthreemonthsLD50(medianlethaldose):thedosethatkills50%ofanimalsED50(medianeffectivedose):thedosecausingtherapeuticeffectsin50%ofexperimentalanimalstherapeuticindex=LD50/ED50
新药研发医学知识培训第24页
新药研发医学知识培训第25页Significanceofpreclinicalstudydeterminethepossibilityofconductingclinicaltrialspredictpossibletoxicityandsafetyrangeinmanprovidereferenceforselectionofinitialdoseinclinicaltrials新药研发医学知识培训第26页6.3Clinicaltrails:PhaseⅠ:smallscalestudieson20-30volunteerstoprovethesafetyinmanaswellasthetolerability,thewholeprocesslast6to9months.dose-rangingstudy(剂量递增试验):todetermineappropriatedosesfortherapeuticuseandtolerability(maximumtolerateddose最大耐受剂量)rmedconsent(知情同意书):informationaboutaparticulartreatmentortestforsubjectstodecidewhetherornottoundergosuchtreatmentortest.
新药研发医学知识培训第27页PhaseⅡ:randomized,controlledandblindstudyareusedtodeterminethetherapeuticeffect,indicationandadversereactionofthenewtherapeuticagentonpatients,thetestsubjectsshouldbenolessthan100pairs.PhaseⅢ:largescalestudy(usuallyinmulti-centerstudyworldwide)tofurtherevaluateefficacyandsafetyofthenewdrug.thetestsubjectsshouldbenolessthan300.Afterphase3studies,anewdrugapplication(新药申请)issubmittedtotheregulatoryauthoritieswitharequestforproductlicense.
新药研发医学知识培训第28页PhaseⅣ:post-marketingstudyunderwideapplicationofthenewdrugtoexaminethetherapeuticeffectsandadversereactionsofthenewdrugaswellastodiscovernewindicationsandadversereactionsthatwerenotuncoveredbefore.Thetestsubjectsshouldbenolessthan.
新药研发医学知识培训第29页Withdrawalofcerivastatin(西立伐他汀)formthemarket:Cerivastatinisasyntheticmemberoftheclassofstatinsusedtolowercholesterolandpreventcardiovasculardisease.Itwasmarketedinthelate1990s.Duringpost-marketingsurveillance,52deathswerereportedinpatientsusingceriv
温馨提示
- 1. 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。图纸软件为CAD,CAXA,PROE,UG,SolidWorks等.压缩文件请下载最新的WinRAR软件解压。
- 2. 本站的文档不包含任何第三方提供的附件图纸等,如果需要附件,请联系上传者。文件的所有权益归上传用户所有。
- 3. 本站RAR压缩包中若带图纸,网页内容里面会有图纸预览,若没有图纸预览就没有图纸。
- 4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
- 5. 人人文库网仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对用户上传分享的文档内容本身不做任何修改或编辑,并不能对任何下载内容负责。
- 6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
- 7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。
最新文档
- 山东美术出版社小学四年级下册品德与社会教案 全册
- 川教版小学信息技术四年级下册教案-全册
- 2024年冷链行业发展趋势分析:我国冷链需求总量约3.5亿吨
- 600字阅读心得模板
- 2050后的我范文模板
- 2024-2025学年高中英语高一上册上海新世纪版教学设计合集
- 2024年安全生产月口号
- 200字目标与计划
- 2024-2025学年高中化学必修 第二册鲁科版(2019)教学设计合集
- 江西绿色生态 景德镇青白瓷 日用瓷(征求意见稿)
- 2020-心肌梗死后心力衰竭防治专家共识
- 2024全新消防维保合同终止协议下载2024
- 《语言文字运用》课件
- 身体机能的测量与评价
- 二级公立医院绩效考核三级手术目录(2020版)
- 医院感染控制标准执行案例手术室管理
- 北京圆明园文化历史
- 2024年四川航空股份有限公司招聘笔试参考题库含答案解析
- 透析器过敏反应护理查房课件
- 砂砾石台背回填方案、交底
- 品牌授权工厂生产授权书合同
评论
0/150
提交评论