藥用高分子

Chapter1FundamentalsofPharmaceuticalPolymerChemistry1
1.1TheConceptofaPolymer1
1.2AdditionPolymerization4
1.3ChainBranching;GraftandBlockCopolymers15
1.4PolymerStructureandProperties18
1.5TechnologyofPolymerization24
1.6ThePrincipalMonomersandTheirPolymers27
1.7PhysicalPropertiesofMonomers37
References41

Chapter2PharmaceuticalPolymers:PrinciplesandStructures42
2.1Introduction42
2.2IntraandInterPolymerMolecularInteractions45
2.3MolecularMass:PolydispersivityandEffectsonPolymerViscosity47
2.4ThermalProperties:EffectofCrystallineandAmorphousPhases51
2.5MechanicalPropertiesofPolymers54
2.6PharmaceuticalPolymers:Principles,Structures,andApplicationsofPharmaceuticalDeliverySystems61
References80

Chapter3PolymersasDrugs81
3.1Introduction81
3.2PolymersforMolecularSequestration83
3.3PolyvalentInteractionsandAnti-InfectivePolymericDrugs95
3.4PolymericDrugsfortheTreatmentofAutoimmuneDiseases105
3.5PolymericAnti-ObesityDrugs107
3.6PolymerTherapyforSickleCellDisease111
3.7ConclusionsandOutlookonPolymersasDrugs112
References113

Chapter4PharmaceuticalApplicationsofNaturalPolymers114
4.1Introduction114
4.2PortalsofDrugAdministrationintheHumanBody116
4.3TransdermalDrugDeliveryDevices117
4.4TopicalDrugDelivery124
4.5OralDrugDeliverySystem131
4.6ParenteralDrugDeliverySystems132
4.7NasalDrugDeliverySystems134
4.8Hydrogel-BasedDrugDeliverySystems136
References147

Chapter5HydrophobicPolymersofPharmaceuticalSignificance149
5.1Introduction149
5.2ExamplesofHydrophobicPolymersandTheirDrugDeliveryApplications150
5.3Conclusions167
References168

Chapter6PolymersinDrugDelivery169
6.1EvolutionofDrugDosageForms169
6.2PolymerExcipients172
6.3PolymersasManufactureAidsandSustainedRelease174
References200

Chapter7PharmaceuticalNanotechnology:OvercomingDrugDeliveryChallengesinContemporaryMedicine202
7.1ChallengesinDeliveryofContemporaryTherapeutics202
7.2NanotechnologySolutions207
7.3IllustrativeExamplesofNanotechnologyProducts211
7.4MultifunctionalNanotechnology218
7.5RegulatoryIssuesinNano-pharmaceuticals225
7.6ConclusionsandFutureOutlook235
References235

Chapter8ThermalAnalysisofPharmaceuticalPolymers237
8.1Introduction237
8.2TheoreticalBackgroundofThermalAnalysis238
8.3PhysicalandChemicalPhenomenaCommonlyInvestigatedUsingThermalApproaches244
8.4ApplicationsofThermalAnalysisfortheCharacterisationofPharmaceuticalRawMaterials248
8.5ApplicationsofThermalAnalysisfortheCharacterisationofPharmaceuticalDosageForms250
8.6Conclusion255
References255

Chapter9ApplicationsofAFMinPharmaceuticalPolymers256
9.1Introduction256
9.2UseofAFMinPharmaceuticalSciences263
9.3AFMCombinedWithOpticalorSpectroscopicTechniques271
9.4Summary271
References273

Chapter10RheologyinPharmaceuticallyUsedPolymers274
10.1Introduction274
10.2TheoreticalBackgroundandFundamentalConcepts275
10.3PracticalIssuesofRheologicalMeasurements289
10.4ApplicationoftheTechnique292
10.5Summary297
References297

藥用高分子（Pharmaceuticalpolymers）是具有生物相容性、經過安全評價且應用於藥物製劑的一類高分子量藥用輔料。藥用高分子作為藥物緩釋載體，包覆在藥物表面保護小分子藥物使其在短時間內不會被生命體吸收，同時隨血液流動到特定區域，在特定區域藥物表面的高分子材料溶解到血液中，釋放出藥物，而本身最終隨體液排出。藥用高分子的主要應用有：①載體，用以控制藥物緩慢釋放，一般由有機矽橡膠、聚甲基丙烯酸酯類等製成封閉細管、微囊或薄膜。②主藥，有長效的特點，其結構有三類：（a）在高分子側基上連接小分子藥物，這類結構最受重視，即高分子親和藥物，在高分子側鏈上除含有藥物結構外，在較遠端側鏈上還含有親水結構、配基或酶，以提高藥用高分子在體內分佈的專一性；（b）在高分子主鏈中含小分子藥物；（c）高分子中不含小分子藥物，其本身可作為藥物或功能試劑。

本書結合現代藥劑學的發展以及作者多年來的教學科研實踐，根據國內外最新資料，簡述了有關高分子化學和物理的基本內容，概述了與藥劑學相關的高分子材料基本知識，重點介紹國際上經法定程式驗證及實際生產中已被採用的藥用高分子材料的原理和應用，充實了國外近年來備受矚目的給藥系統用天然來源藥用高分子及可生物降解的合成藥用高分子和複合物的有關內容，此外，還對熱分析、原子力顯微鏡和流變學在藥用高分子領域中的應用進行了闡述。本書可供普通高等醫藥院校藥學、藥物製劑、製藥工程、高分子材料與工程等相關專業學生及從事藥物製劑生產、研究的人員參考使用。

全書共分為十章，參與本書編寫的人員及具體編寫分工如下：第一章由孫紅、王者輝編寫；第二章由張宏志、孫立平編寫；第三章由鞏學勇、劉鳳霞編寫；第四章由李慶傑、常海濤編寫；第五章由鄭超、張倩編寫；第六章由劉光耀、江棟編寫；第七章由衛振華、劉愛軍編寫；第八章由王者輝、李寶慶編寫；第九章由杜江山、劉振亮編寫；第十章由姜洪麗、孟憲鋒編寫；全書由王者輝統一整理並任主編。

由於水準所限，書中不足之處在所難免，誠懇希望廣大讀者加以批評指正。

編者
2018年5月

Pharmaceuticalpolymers(bothsyntheticandnatural-basedpolymers)havefoundtheirwayintothepharmaceuticalindustriesandtheirapplicationsaregrowingatafastpace.Thedesirablepolymerpropertiesinpharmaceuticalapplicationsarefilmforming(coating),thickening(rheologicalmodifier),gelling(controlledrelease),adhesion(binding),pH-dependentsolubility(controlledrelease),solubilityinorganicsolvents(tastemasking),andbarrierproperties(protectionandpackaging).Majorapplicationsofpolymersincurrentpharmaceuticalfieldareforcontrolleddrugrelease.Fromthesolubilitypointofview,pharmaceuticalpolymerscanbeclassifiedaswater-solubleandwater-insoluble(oilsolubleororganicsoluble).Manywater-solublepharmaceuticalpolymersincludingpolyethyleneglycol,polyvinylalcohol,polyethyleneoxide,polyvinylpyrrolidone,polyacrylateorpolymethacrylateesters,cellulosebasedpolymers,hydrocolloids,andmanyplasticsandrubberswillbetabulatedandtheiranionicandcationicfunctionalitiesaresummarizedanddiscussed.PEGylationisdefinedasthecovalentattachmentofpolyethyleneglycol(PEG)chainstobioactivesubstances.

Pharmaceuticalpolymer,akindofmacromolecularcompoundwithbioco-mpatibility,safetyevaluation,isusedasakindofhighmolecularmasspharma-ceuticalexcipientsfordrugpreparation.Asasustainedreleasedrugcarrier,thepharmaceuticalpolymeriscoatedonthesurfaceofthedrugtoprotectsmallmolecularweightdrugsnottobeabsorbedbythelivingbodyinashorttime.Atthesametime,withtheflowofbloodinaspecificarea,thepolymermaterialsonthespecificareaofthedrugdissolveintothebloodandreleasethedrug,andthedrugitselfiseventuallydischargedwiththebodyfluid.Themainapplicationsofpharmaceuticalpolymersinclude:(1)thecarrier,whichisusedtocontroltheslowreleaseofdrugs,usuallymadeoforganosiliconrubber,polymethacrylateandothersintheformofclosedtubes,microcapsulesorfilms.(2)themaindrugwithcharacteristiclongtimeefficacyhasthreekindsofstructures:(i)polymericaffinitydrug,withthehydrophilicgroups,theligandsorenzymesonthefarendofthechain,havesmallmoleculardrugsconnectingonthesideofthepolymerchains,whichisthemostimportantstructurewithpharmaceuticalpolymeruniformdistributioninsidethebody;(ii)polymericdrugcontainssmallmoleculedrugsinthemainchain;(iii)polymersdonotcontainsmallmoleculardrugs,itactasmedicineorfunctionalreagent.

Thisbook,combinedwiththedevelopmentofmodernpharmaceuticsandmanyyearspracticeofteachingandscientificresearch,brieflydescribesthefounda-mentalsofpolymerchemistryandphysics,andsummarizesthebasicknowledgeofpolymersrelatedtopharmaceutics.Accordingtothelatestinformationathomeandabroad,thisbookmainlyintroducestheprinciplesandapplicationsofpharma-ceuticalpolymersthathavebeenusedininternationallegalprocedureverificationandactualproduction,andenrichestherelatedcontentsofnaturalsourcesofpharmaceuticalpolymersandbiodegradablesyntheticpharmaceuticalpolymersandcomplexesinrecentyears.Theapplicationsofthermalanalysis,atomicforcemicroscopyandrheologyinthefieldofpharmaceuticalpolymersareincluded.Thisbookcanbeusedasareferenceforreadersofpharmaceuticalengineering,polymermaterialsandengineeringandrelatedmajorsandpeopleengagedintheproductionandresearchofpharmaceuticalpreparations.

Thepersonnelinvolvedinthisbookinclude:thefirstchapterbyHongSunandZhehuiWang;thesecondchapterbyHongzhiZhangandLipingSun;thethirdchapterbyXueyongGongandFengxiaLiu;thefourthchapterbyQingjieLiandHaitaoChang;thefifthchapterbyChaoZhengandQianZhang;thesixthchapterbyGuangyaoLiuandDongJiang;theseventhchapterbyZhenhuaWeiandAijunLiu;theeighthchapterbyZhehuiWangandBaoqingLi;theninthchapterbyJiangshanDuandZhenliangLiu;thetenthchapterbyHongliJiangandXianfengMeng;thiswholebookiseditedbyZhehuiWang.

Astothelimitationoftheauthors’level,allkindsofcriticismsarewelcomeforvariousmistakesinthebook,andwesincerelyhopethatreaderswillbeabletoinformusforcorrection.

ZhehuiWang
2018.5