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含马齿苋及牛油果树提取物的保湿霜治疗脂溢性皮炎的临床研究

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硕士学位论文学校代码!Q三33密级公珏

含马齿苋及牛油果树提取物的保湿霜治疗脂溢性皮

炎的临床研究

ClinicalefficacyofmoisturizercontainingextractsfromPortulacaoleraceaandavocadoin

acohortofseborrheicdermatitispatients

论文答辩日期作者姓名:

学科专业:

研究方向:

学院(系、所):

指导教师:

KarishmabyeBabajee

临床医学

皮肤病与性病学

湘雅医院

李吉副研究员

答辩委员会主席

中南大学

二零一三年五月

原创性声明

本人声明,所呈交的学位论文是本人在导师指导下进行的研究工作及取得的研究成果。尽我所知,除了论文中特别加以标注和致谢的地方外,论文中不包含其他人已经发表或撰写过的研究成果,也不包含为获得中南大学或其他单位的学位或证书而使用过的材料。与我共同工作的同志对本研究所作的贡献均已在论文中作了明确的说明。

作者签名:

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作者签名:——导师签名——日期:——年一月一日

硕士学位论文ABSTRACT

ABSTRACT

Background:Seborrheicdermatitis(SD)isacommon,chronicrelapsinginflammatoryskindisease.Althoughthecurrenttreatmentsareeffective,theireffectsareoftentransient,andtheirsideeffectsarenon—negligibleaSwell。RecentresearcheshaveshowedthatabnormalitiesofskinbarrierplayimportantrolesinthepathogenesisofSD,whichis

clinicallyobservedbythepresenceofdryskin.Moisturizershavebeen

damagedskinbarrierandhaveproventohaveaneffectonrestoringthe

beenusedtotreatabnormalskinbarrier-relateddiseasessuccessfully.Sowespeculatedthatmoisturizerscouldrebuildtheskinbarrierfunction,andcouldbeusedinthetreatmentofSD.

Objeetive:Toevaluatetheclinicalefficacy,safetyandchangeinbiophysicalindices(TEWL,skinhydration,elasticity,sebumcontent,pH,

melaninanderythemacontent)duringuseof

amoisturizercontaining

extractsfromPortulacaoleracea(Purslane)andavocadoonpatientswithSD.

Methods

1.98patientswithmildtomoderateSDwereenrolledinthisstudy.2.ThepatientsreceivedtreatmentofamoisturizercontainingPortulacaoleracea(Purslane)andavocadotwicedailyfor28days.3.111eseverityofthelesionswasestimatedandscoredbyadermatologistuponarrival(dayO),duringtreatment(day7,14)andattheendofthetreatment(day28).

4.Thepatients’satisfactionandthetherapeuticsafetywerealsoassessedontheabovedates.

5.Biophysicalindicesweremeasuredusingamulti-probeadapterm5

system仔omCourageandKhazakaasfollows:

a。corneometerCM825forskinhydrmion,

b.tewameterTM300forTEWL,

c.sebumcassetteSM815forsebumcontent.

d.skinpH-meterPH905forpH,

e.cutometerMPA580forskinelasticity,

£mexameterMXl8formelaninanderythemacontent

硕士学位论文ABSTRACT

6.Theresultsweremeasuredonday0,7,14,28andratioswereplottedgraphically.

Results

1.AsignificantimprovementofSDpatientswasobservedfromDOtoD28.

2.TheimprovementwasmostsignificantduringthefirstweekoftreatmentwiththescoresoftheSDpatientsdecreasingby59.3%onD7.Furtherdecreaseof87.4%wasnotedbyD28.3.Surveyofthepatients’self-assessmentshowsthat31%ofthe

patientsexperiencedmajorimprovementand63%completeclearanceoftheSD.

4.Safetywashighasveryfewandmildsideeffectswereobservedandnotreatmentinterruptionwasneeded.

5.Skinbarrierfunctionstudiesshowedthatthismoisturizerhadaneffectofdecreasingthesebumcontent,improvinghydration,reducingtransepidermalwaterloss(TEWL),decreasingtheerythemaindex,andslightlyincreasingthemelanincontent.6.TheskinpHandelasticityremainedfairlystablewiththeuseofthemoisturizer

Conclusion:ThemoisturizercontainingextractsfromPortulacaoleraceaandavocadorepairstheskinbarriersignificantly,whilehavingsignificanttherapeuticeffectsinmildtomoderateseborrheicdermatitiswithoutsignificantsideeffects,andhence,providesanew,effectivetreatment.

KEYWORDS:Seborrheicdermatitis,skinbarrier,moisturizer

硕士学位论文目录

目录

原创性声明………………………………………………………………………………IABSTRACT…………………………………………………………………………………………………。IICHINESEABSTRACT…………………………………………………………………………………。1ABBREVIATIONS…………………………………………………………………………………………3ClLU’TER1:INTRODUCTION…………………………………………………………………….41.1ETIOLOGYANDEPIDEMIOLOGYOFSD……………………………………………………….41.2CLINICALFEATURESOFSD……………………………………………………………………….61.3TREATMENTOFSD…………………………………………………………………………………..71.4SDANDTHESKINBARRIER.......….….…………………….……………….……………….….71.5THEMOISTURIZERUNDERSTUDY………………………………………………………………91.6MEASUREMENTOFSKINBARRIERFUNCTION……………………………………………l1CHAPTER2:MATERIAI.SANDMETHoDS………………………………………………142.1PATIENTS………………………………………………………………………………………………142.2STUDYPROTOCOL………………………………………………………………………………….142.3EFFICACYANDSAfETYASSESSMENTS………………………………………………………15CHAPTER3:STATISTICALANAIⅣSISANDRESUITS…………………………….173.1STATISTICALANALYSIS……………………………………………………………………………173.2EFFICACYEVALUATION…………………………………………………………………………..173.3TOLERABILITYANDSAFETYASSESsMENT…………………………………………………253.4SKINBARRIERFUNCTIONEVALUATION…………………………………………………….25CHAPTER4:DISCUSSION…………………………………………………………………………30REFERENCES……………………………………………………………………………………………。33LITERATUREREVIEW………………………………………………………………………………42ACKNOⅥ几EDGEMENT……………………………………………………………………………。57

硕士学位论文CHINESEABSTRACT

CHINESEABSTRACT

背景

脂溢性皮炎(SD)是一种常见的,反复发作的炎症性皮肤病。目前的治疗虽然是有效的,但其效果往往是短暂的,且副作用不可忽视。临床上观察至IJSD患者皮肤干燥等表现说明SDftO发病与皮肤屏障异常有密切的关系。医用保湿霜已被证明有恢复受损皮肤屏障的作用,并已成功用于某些与皮肤屏障异常有关疾病的治疗。因此,我们推测医用保湿霜可以通过重建皮肤屏障功能从而治疗SD。目的

评估含马齿苋和牛油果树提取物的保湿霜治疗SD的临床疗效,安全性和生理指标的变化(TEWL,皮肤水分,弹性,皮脂含量,pH值,黑色素和红斑含量)。

方法

1.98例SD患者参与这项研究。

2.患者接受含有马齿苋和牛油果树提取物的保湿霜治疗28天,每日两次。

3.患者治疗前(DO),治疗中(D7,D14)及治疗结束后(D28),由皮肤科医生根据患者情况评分,评估病情的严重程度。

4.在上述时间,同时对患者的满意度和治疗的安全性也进行了评估。

5.用多探头适配器MPA5系统测定患者皮肤生理指标,如下:

①ComeometerCM825检测皮肤含水量;

@TewameterTM300检测TEWL;

③皮脂检测探头SM815检测皮脂含量:

④pH计PH905检测皮肤pH值;

@CutometerMPA580检测皮肤弹性:

⑥mexameterMXl8检测黑色素和红斑量。

6.上述生理指标在DO,D7,D14,D28检测,并根据结果作图。

结果

1.从D0到D28,SD患者病情显著改善。

2.治疗的第一周患者病情改善最为显著,D7相对于DO患者病情评分下降59.3%,D28时病情评分下降达87.4%。

3.在治疗的第28天,31%的患者自评病情显著改善,63%患者自评病情完全

硕士学位论文CHINESEABSTRACT

治愈。

4.治疗过程中,只有极少数患者有轻微的刺激反应,没有患者因为副作用而需要中断治疗。

5.皮肤屏障功能的研究表明,使用该医用保湿霜能降低皮脂含量,提高皮肤含水量,减少经表皮失水(TE肌),并减少红斑指数。

6.使用该医用保湿霜,皮肤的酸碱度和弹性保持稳定。

结论

含马齿苋和牛油果树提取物的保湿霜能有效地改善SD患者皮肤屏障功能,疗效显著,副作用小,是一种全新的、有效的治疗脂溢性皮炎的方法。

关键词

脂溢性皮炎,皮肤屏障功能,医用保湿霜

硕士学位论文ABBREVIATl0NS

ABBREVIATIoNS

SD:seborrheicdermatitis

TEWL:transepidermalwaterloss

SC:stratumcomeum

硕士学位论文Chapterl:INTRODUCTION

Chapter1:INTRODUCTION

1.1EtiologyandepidemiologyofSD

Seborrheicdermatitis(SD)isacommon,recurrent,relapsinginflammatoryskindisorderwhichaffectsabout11.6%ofthegeneralpopulation.…30—42%ofthisnumberconsistsofyoungadults.例InHIV-positiveindividuals,itisfairlycommon,particularlyinthosewhohaveaCD4T-cellcountofbelow400cells/mm3.Theprevalenceranges

from20-83%.【jJSDhasabimodalpresentation,occurringinnewborninfantsupto3monthsofage,andadultsof30—60yearsold.…Thefactthatthediseaseoccursininfancy,andimprovesbeforerelapsinginpostpuberty,suggeststhattheremayexistarelationshipwithsexhormones.Malehormones(androgens)stimulatesebumproduction,probablyexplainingwhythereisamalepredilectionto

SD.ThereseemstobeanethnicAfhcan—Americans.【5】SDlesionsareseenexacerbateinwinter.[41

preference,withlesscasesseenintoimproveduringthewarmermonths,and

TheimportanceofstudyingSDisoftenoverlooked,andshouldbegivenmoreemphasissinceitisnOWknowntocausesocialstigma,lossofself-esteem

andpsychologicaltrauma.[2,6,71Moreover,itsprevalencebeinghigh,SD

hasahighsocio.economicimpact,reflectedbytherisingcostsofhealthcare.

Inthe1950s,researchersfocusedmainlyontryingtodeterminearelationshipbetweenSDand

vit锄insB2,B6,B12andbiotin.[8-141However,noassociationhasbeenfoundyetbetweennutritionaldeficienciesandSD.【15JBasedonrecentfindings,theetiologyofSDcanbecategorizedunderthreefactors:sebaceousglandsecretions,micronoralmetabolism.andindividualsusceptibility.【16'17】ThepattemofSDreliesontheinterdependenceofthesethreefactors.

硕+学位论文Chapter1:INTRODUCTION

SD

Fig1three—factorcausalmodelforSD

SDisnotadiseaseofthesebaceousglands,evenifsebo口headoesprovideapredisposition,permittingthegrowthofyeastsofthegenusMalasseziaindeed,sebaceousglandactivitybecomesimportantinthepathogenesisofSDmainlyinthepresenceofMalassezia,whichdegradesebumandconvertspecificsaturatedfatty

acidstounsaturatedfattyacids.resultingininflammationm

TheincidenceofSDin

infants(cradlecap),improvementafterinfancy,riseinadolescenceandpost—puberty,anddeclineagainlatersuggestacorrelationbetweenSDandsebumMoreoveLsebum—richareaslikethescalp,nasolabialfolds,ears,eyebrows,chestandbackaremorepronetoSD㈣PatientswithneurologicaldiseasessuchasParkinson’shaveahighertendencytodevelopSDduetotheincreaseinmalesexhormonesandtheireffectsonthesebaceousglandsWhenthesepatientsarctreatedwithlevodopafortheirParkinson’sdiseaseanimprovementinSDisalsoseon㈣24】Patientssufferingfromneuroleptic—inducedParkinsonism,familialamyloidoticpolyneuropathy,cerebrovascularaccidents(CVA),traumaticbraininjury,eraniosynostosis,traumaticspinalcordinjury,epilepsyandfacialnerveparalysisalsoshowahigherincidenceofSD[2530]

TherealsoseemstoexistastrongcausallinkbetweenSDandskincolonizationwiththeyeastsofthegenusMalassezia㈣ThesearenormalskineommengalsbutinSDtheyshowanabnormalimmuneresponseThevastmajorityofrecentdataadirectlinkbetweenSDandthismicrobialawide

硕士学位论文Chapter1:INTRODUCTION

ofdrugs,suchaSpyrithionezinc,seleniumsalts,andspecificazolesresultinmajorimprovementofSD,withtheonlyknownfunctionallinkbetween

thesematerialsbeingantifungalactivity.【31JThesecondsupportingargumentisthatimprovement

inscalpSDoccurshand—in-hand

withreductioninlevelsofMalassezia.【32’33JManystudiesweretryingtofindoutthespeciesofMalasseziamostprevalentinSD.AmajorityofM.furfur(35%)wasfoundinastudydoneonSDpatientsbyNakabayashieta1.【34,351However,Rendiceta1.foundagreaterconcentrationof

M.globosa(67%),followedbyM.缸furandM.sympodialis.。刈Asimilarfindingwasalso

reportedbyGuptaandGaltanis.‘37'381

TajimawastheonlyauthortoreportM.

restrictaasbeingmostprevalent.[39]

Malasseziamaycontributethroughitslipaseactivityonlipidsfoundontheskinsurface--releasinginflammatorysaturatedandunsaturatedfreefattyacids--andfromitsabilitytoactivatethealternativecomplementpathway.【17'40,41]ThequantityofMalasseziaisnotconsideredasadeterminingfactorforaninflammatoryreaction.p纠DespitethefactthatMalasseziaiSaknownskincommensal,somepeoplearemorepronetodevelopingSDthanothers.Itishypothesizedthatindividualsusceptibilitymightplayaroleinthateffect,butthespecificdifference

betweentheseindividualsremainsunclear.SDisalsocommonlyaggravatedbychangesinhumidity,changesin

seasons,trauma(eg,scratching),andemotionalstress.¨刈

1.2C!linicalfeaturesofSD

TheclinicalpictureofSDdiffersaccordingtotheagegroupaffected.Theinfantileformpresentsmostcommonlyonthescalp(cradlecap)andisseenaserythematousflakingpatchesofvaryingextentsandintensity.【4驯Othersiteswhichcarlbeaffectedaretheface

andthebodyfolds,suchastheretroauricularregion,neck,axillaeandinguinalregion.Theadultformischronic,asopposedtothe

infantileformwhichisself-limiting.[44】ItCanrangefromamildtomoderateerythematopapular,exudativeand/orsquamouslesions,whichWaXandwaneovertimeandmaybeexacerbatedbvstressandfatigue.【15’45】Theareasaffectedareasfollows:face(87.7%),scalp(70.3%),chest(26.8%),lowerlimbs(2.3%),upperlimbs(1.3%)andothersites(5.4%)suchasbodyfolds.[46]Thelesionsconsistofpoorly—definedmaculesorthinplaqueswithoverlyingwhite,oryellowgreasyscales.Itchingmayormaynotbepresent.Thescalplesionsrangefrommilddesquamation(pytiriasissimplexcapitisordandruf0toyellowcrusts

affixedtothescalpandhair(pseudo

tineaamiantacea).Inthebodyfolds,thelesionsmayacquireamaceratedappearanceandmayalsoleadtofissuresandsecondaryinfection.

1.3TreatmentofSD

Effectiveandlong-termtreatmentsarenecessaryforSD

patientssince

Malasseziaarecommensalmicrobeswhichwillreturn

uponcessationoftherapy.Thetherapyshouldalsobeusedaspartofaroutinecareregimen,whilebeingcosmeticallyacceptable,inordertoimprovepatientcomplianceandensureremissionforalongperiodoftime.Currently,thetherapeuticarsenalforthecontrolofSDiSextensive.1151TopicalandsystemicantifungalsarebeingusedsuccessfullytodecreasethecolonizationoflipophilicMalasseziaspeciesandalleviatethesymptoms

andsignsofSD.However,comparedto

topicalsteroids,antifungalsshowarelativelyslowonsetofanti.inflammatoryeffect.[47,48】TopicalsteroidsarealsowildlyusedtoreduceinflammatoryreactionofSDpatients.【321Frequentrelapsesafterthecessation.highcostandsideeffectsonlong-termusage(1ikeskinatrophy,hypertrichosisandsteroid-dependentdermatitis)restricttheuseofcorticosteroids.

Inordertoavoidthesideeffectsoftopicalsteroids,calcineurininhibitorslikepimecrolimusandtacrolimus,duetotheirs仃onganti-inflammatoryandanti—fungaleffects,havebeenrecommendedinSDtreatmentinrecentyears.1491However-theprofileforlong—termuseoftacrolimusandpimecrolimusremainscontroversialbecauseofthepotentialdependencyandsideeffectsafterlong—termuse,andmorestudiestostudylong-termtherapyareneededforthisclassofdrugs.【50]Therefore.wet11i11kitisnecessarytodevelopasafeandeffectivealternativetreatmentforSD.

1.4SDandtheskinbarrier

ThevisiblesymptomsofdesquamationanderythemainSDareinfact

reflectionofanunderlyingdisturbedskinbarrier,t51】OneofthemainfUnctionsof

theskin,thatistoactasabarrierprotectingthemammalianorganismagainsttheexternalmilieu,islargelycarriedoutbythestratumCOiTleum(sc).Whenwerefertotheskinbarrier,wewanttoputemphasisontheepidermisandthestratumcomeum(sc).ThequalityoftheSC,afactoroftenleftout,maybeimportantindrivingindividualsusceptibilitytoSD.【52]

Innumerabledefinitionshavebeenproposedtotryto

demystifyandshedlighton

theanatomyoftheskinbarrier.Radical

changeshavetakenplaceoverthepast50

硕士学位论文Chapter1:INTRODUCTION

yearsontheconceptt11attheskinbarrierISamere”mantle”thatseparatestheinternalmediumfromtheenvironment.Thebeliefthattheskinbarriercomprisesonlyoftheupperlayersofthestratumgranulosum,andnottheSC,wasmodifiedbytheanalysisofCristopherandKlingmaninthe1960s.【53]Ataroundthesametime,studiesonthepermeabilityoftheskinbarrierwerecarriedoutbyBlank[54】,andScheupleinandBlank[551,demonstratingtheimportanceofthechemicalparticularitiesofthemoleculeandthethicknessoftheSC.Theexternalfactorofenvironmentalhumidity,whichalsoplaysaroleinthepermeabilitybarrierhomeOStasis.wasanalyzedbvSatoeta1.almost30yearslater.【56]

The‘’bricksandmortar”concept,nowadaysviewedasthemostappropriatemodelfortheunderstandingofcellulararrangementintheskinbarrier,wasproposedin1975byMichaelseta1.【57】,andvalidatedin1997byJohnsoneta1.嗍Accordingtothisanalogy,theCOrrleocytesformthebricks,andtheintercellularlipidsformthemortar.Thematrixlipidsarecomprisedoffreefattyacids,cholesterol,andceramides,whichareorganizedintolamellaurmembranes.[59,60]

Indeed,theSCisadverselyaffectedbythepathologicalmechanismsgivingrise

andexhibitsuncontrolledtoskindiseases.ItshowsahyperproliferativestateinSD

growthandmaturationofcomeocytes,whicharenotreadytobeshedfromtheskinsurface.[61]TheSCalsoplaysacrucialroleintheinflammatoryresponseofSD

andangiogenesis.Anelectronthroughmelanocyteactivation,flbroplasias

microscopicstudyofSD-affectedSCshowedfeaturesconsistentwithhyperproliferationsuchasparakeratoticnucleiretention,intracellularlipiddroplets,areducedquantityofdesmosomes,irregularcomeocyteenvelopestructure,intercellularMalasseziayeasts,andmassivequantifiesofunstructuredintercellularlipids.[511

Hence,disruptionoftheskinbarrierplaysacriticalroleintheinflammatory

abnormaldesquamation,responseinSD.Compromisedskinbarrier,reflectedby

xerosisanddiminishedskinhydration,hasbeenrecognizedasoneofthemostimportantfactorinthepathogenesisofSD.【62】AnytreatmentwhichCanfl】nllerdisturbtheskinbarriercaileventuallyexacerbatethedisease.Moreover,sincetheskinbarrierremainsthetargetsitefortopicaldermatologicaltherapy,itisofutmostimportanceto

minimumofinsult.

encouragetherapieswhichexposesittoa

TheSCprotectstheinternalmilieubyactingasabarrieragainstexternalinsultsandtoxins.【631However.themostimportantfunctionoftheSCistoretardwaterloss

fromtheskin,actingasanepidermalpermeabilitybarrier(EPB),tomaintainhydration,flexibility,integrityandhealthoftheskin.163】Lossofthisfunctioneventuallyleadstodecreasedfunctionalityoftheskinbarrier,evidencedbythedramaticallyincreasedTEWLinSDsufferers.[64]

TheSCmaintainsitsintegritythroughcorneodesmosomes,whichlinkadjacentcorneocytes.[651Thesecorneodesmosomesarecontrolledbythecoordinatedactivityofvariousclassesofhydrolyticenzymes,[66,67,681whichareinturncontrolledbywateractivityandpHoftheSC.[691Tomaintaintheelegantprocessofdesquamation,andhenceproperskinturnover,skinsurfacehydrationisofutmostimportance.Sebum,whichcanpartitionintotheintercellularlipids,mayalsoperturbthedesquamation

processanddisruptintercellular

lipidorganization.[701

WethinkthatallidealSDtherapyshouldbeabletoabatetheinflammationaswellasrestoretheskinbarrierfunction.Existingtherapies(1ike

antifungals,topicalsteroids,andcalcineurininhibitors),despiteprovidingrelief,maynothaveasignificantroleinrepairing

theskinbarrierdefectspresentinSD.Previousstudieshaveshownthatshortaswellaslongtermtherapywithtopicalsteroidsnegativelyimpactontheskinbarrierbyinhibitingformationofepidermallipids[71】anddecreasingepidermalproliferationanddifferentiation.【72】

Similarly,topicalcalcineurininhibitorsliketacrolimusandpimecrolimus,nowextensivelyusedasareplacementfortopicalsteroidsininflammatoryskindiseases,canimpactnegativelyonthefunctionsoftlleSC.aswellasitsintegrityandpermeability,asshownbyastudyrecentlyconductedbyMinjeongeta1.(73】Thecorrectuseofmoisturizersandcleansersisimportantinpatientswith

dermatologicaldisease.Forthepurposeofprimarilyimprovingtheskinbarrier

functionwhileabatingthesignsandsymptomsofSDatthesametime,weused

moisturizercontainingextractsfromPortulacaoleraceaandavocadoin

ourstudy.1.5Themoisturizerunderstudy

Moisturizers,representingagroupofproductsdesignedforskincareandhygiene,areatypeofcosmeceuticals.CosmeceuticalsarecosmeticsWithbiologicallyactiveingredientspurportingtohavepharmacologicalbenefits.Theyrepresentamarriagebetweencosmeticsandpharmaceutics.Cosmeceuticalsareusedfornourishing,hydratingaswellaSimprovingtheappearanceoftheskin.Theyarealsodocumentedaseffectiveagentsfortreatingvariousdermatologicconditions,like

atopicdermatitis,psoriasisandSOon.[741Cosmeceutical

preparations丘omherbalon91n,beingmostlynon-toxic,areverypopularamongcons啪erS.【75]Theboo觚ng

marketofcosmeceuticalsinrecent

yearsisbeingdrivenbyconsumerinterestandmesabype.

AmoisturizerISall

agentdesignedtoincreasethesoftnessandpliabilityoftheSC?Moisturizers,attimes,arereferredtoashumectants,锄01lients,1ubdcants,oils.

alldgreases;however,thesetermsarenotinterchangeable.Moi曲uIizers

arepossibly

memostcommon

productprescribedbydermatologists,andhavebeenthesubjectof

mucntiascinationmrecent

yearsregardingtheirtherapeuticeffects.Withthe

l(110wledgethattheSCisadynamicandinteractivetissue,muchemphasisis

being

placedonsubstancesthatCanactuallyabletopreventskindamage.moisturizetheskin,sincethisis

thoughttobe

1hemoisturizercontainingextractsfrom

Portulacaoleracea(PurslarIe)aIld

avocadoasitsmajoractivecomponents,isa

productwhichiswildlyusedinC11ina.IIl

recentresearches,ithasbeenshownthatPurslaneisrichinvariousbioactive

and

phenolicanti’oxidants,aswellasOmega-3fattyacids,whichhelpin

strengthening

theimmunesystem.u…Researchhasalsoshown

significantanalgesicandanti-inflammatorybenefitsontopicalapplicationofPurslane.【77]Ithasalsobeen

snownthattheothermaincomponent,avocadohasvarious

healingproperties.suchasanti。inflammatory,analgesic,rapidre-epithelializationandanti.o虹d础.【78】

Othercomponentsofthemoisturizerinclude

hyaluronicacid,water.s01uble

licoriceextractandSOon.Hyaluronicacidis

awidelydistributedglycos砌noglyeall

whichlikely

playsamulti-facetedroleinthemediationofthecellularandmatrix

eVentsofinflammationintheskin.Ithasa

pro-inflammatoryrole,byenhancing

cellularinfiltrationandhence

promotingwound.healing.[79,80】Italsohelpsmoderate

the1nflammatoryprocess

bystabilizingthegranulationtissuematrix.[79】Presentin也e

extracellularmarxofbasal

keratinoeytes,hyaluronicacidplaysacmcialrolein

maintainingtheintegrityofthedermalcollagenmatrixandin

promotingkeratillocvte

proliferation.州Hyaluronicacidalsohashighwater.retention

abilityandisimportantinmaintaininghydrationandelasticityoftheskinbarrier.[811Thesebenefitsmake

nyaluronicacidanidealhumectant;indeed,its

efficacyhasbeenproveninthe

仃ea:n11entofvariousskindisorders

presentingwithxerosis.【821Another

componentof

oIll"moisturizerlSlicoriceextract,whichhasshown

benefitsininhibitionofmelanogenesisandinflammation.[831

Duetothemoisturizing,non—toxic,anti-inflammatoryandanti-allergyeffectsoftheactivecomponentsinourmoisturizer,weproposedthatitcouldbeusedinthelong—termtreatmentofSD.Despitethemanybenefitsofmoisturizers(cosmeceuticals),nostudieshavebeendoneyettoassessitsactiononSD.【841InOurstudy,weusedittotreat98SDpatients.

1.6Measurementofskinbarrierfunetion

InadditiontodeterminingtheeffectofmoisturizeronSD

patients,wealsoaimedatmeasuringitsimpactontheskinbarrierduringtreatment.SomemoisturizersCallimpairtheskinbarrierevenwhilemakingtheskinappearlessdry,whilesome

ideal臼.e咖entCanrepairtheskinbarrier.[851Asmentioned

earlier,wethinkthatan

shouldalsorestoretheskinbarrierbycounteractingthedisruption

broughtaboutbythedestructivepathogenicprocessesofSD.

Thereliabilityofaclinicalskinexaminationisprecludedbyitssubjectivecomponent.Furthermore,manysubclinicalchangespresentCallbeinvisibletothe

nakedeye.Itis,therefore,becomingmoreandmore

importanttodevisemethodstoincreaseobjectivityinOurmeasurements.Laboratoryskinphysiologystudies,inparticularitsmechanicalproperties,havebeencarriedoutsincethe1960s.In1966,

andWrightpublishedoneofthefirstresearchesbasedonthissubject.[86】TheseRidge

methodologies,alsoknownasskinbioengineeringtechniques,allowforthemeasurementofparameterssuchas1evelofmoistureintheskin,elasticityindex,microcirculationandSOon.【87,88】Equipmenthavebeendevisedinordertoensure

standardizationofthesemethods,andmakereproducibility

possible.[89,901Forthe

sakeofourresearch,weusedtheCourageandKhazaka

multi.probeadapterMPA5systemfromCologne,Germany.Wewereattractedbythefollowingadvantages:a)Objectivequantificationofbiophysicalskinparameters

b)Non—invasivenessandreliability

c)Reproducibilityunderstandardconditions(environmentalhumidity,temperature,time)[911

d)Non—interferencewiththeparticipants’conditionorothertreatments

theymightbeundergoing.[921

Measurementofbiophysiologicalskinindicessuchashydration,TEWL,sebumcontentandpHprovidesameansofassessingtheintegrityoftheskinbarrierinSD.

[891Wealsoassessedtheskin

elasticity,melaninanderythemacontemoftlles姑nin

oIll"patientstoexploreanyothereffectsofthemoisturizer.The

biophysicalindices

aredescribedbrieflybelow.

SkinhydrationindexandTEWL:Skinhydrationisa

quinteSSentialDartofthenormalfunctioningoftheskin,andits

regulationismainlyorchestratedbvthe

complexnatureoftheSC.TheretentionofwaterintheSCis

dependentontwomajor

factors:(1)naturalmoisturizingfactors,whicharelow.molecular

weighthygroscoDicagentspresentwithinthecorneocytesand(2)theorderlyarrangementoftheSCintercellularlipidstoformabarriertoTEWL.[93,94】TherearealsotooleculesDresem

intheSC,whichareconduciveto

maintaininganoptimumlevelofhy蝴ion,suchasglycerol,hyaluronan,andwater-transportingproteinaquaporin.3.【93】Skinhy姗ion

index1SinverselyrelatedtoTEWL.Compromisedskinhydrationand

increasedTEⅥ一in

manyinflammatoryandhyperproliferativedermatologicalconditions

resultsindisturbanceofthemanyprocesses

influencingdesquamation,leadingtotheclinicalappearanceofdry,flakyskin.1941

Inourstudy,tomeasureskinhydration,weusedthe

probeCorneometerCM825.

basedonthecapacitancemethod,whichinturnrelies

onthecompletelydi妇隆rent

dielectricconstantofwamr(81)andothersubstances(usually<7).

Valuesaredisplayedinsystem-specificarbitraryunitsbetween0and130.[95】

ForthemeasurememofTEWL,thetewameterTM300wasused,andisbasedondiffusioninanopenchamber.Thevaluesareexpresseding/m2/h.[961

Sebumcontent:Sebumforms

partoftheSSLF(skinsurfacelipidfilm).whichcomprlsesofsecretionsfromthesebaceousglandsmixedwithlipidsf.romt11ekeratinizingepithelium.PreviouslyviewedaSSClipids,triglyceridesandShon.chajn

ta姆acidshavebeenrevealedasbeingsebaceousin

origin,andratherthanprotecting

theepidermalpermeability

barrier,theymaydisruptthedesquamationprocessbvdisturbingintercellularlipidarrangements.【701InOUrstudy,weusedtheSebumeter

SM815.This

probecomesintheformofasebumcassette,whichisbasedontheprincipleofgrease-spotphotometry.[97】

SkinpH:Asmentionedearlier,theacidic

pHoftheskinmaintainstheintegrity

oftheskinbarrier.Varioustheorieshave

proposedanexplanationfortheoriginof也e

“acidmantle”.Exogenousandendogenousmechanismsall

playacrucialr01e.Threeendogenouspathwaysreleasingurocanicacid‘98】,freefattyacidsfromphospholipids

即’andanonenergy。dependent

sodium-protonexchanger0qI-IEl)[100lhavebeen

showntocontributetothe

acidityoftheskinbarrier.StudieshaveshoⅥmt|1atacute

硕士学位论文Chapterl:INTRODUCTION

increasesinskinpHcanadverselyimpactontheskinbarrierfunction.169]Inourstudy,wemadeuseofthepH-meterPH905toassessthechangeinpHduringthetherapy.ThisprobeusestWOcombinedelectrodes(oneglass矿ionsensitiveelectrode,andonereferenceelectrode、placedinonecompartment.[101]

Melaninanderythemacontent:TheskincolorlargelydependsontheinterplaybetWeenmelaninandhemoglobin(erythema)totem.Ithaslongbeenknownthat

onethehallmarksofinflammationis‘’rubor”,thatistheredcolor.TomeasurethesetWoindices,wemadeuseoftheprobeMXl8,whichisbasedontheabsorption

principle,thatis,lightofthreedifferentwavelengthsisemittedbytheprobe,andthequantityoflightabsorbedbytheskiniscalculated。[102]

Elasticityindex:Skinelasticitydependsonthecollagenamount,aswellasonotherfactorssuchasage,sex,anatomicalsite,tonalTleafew.[103'104,105lAgoodtherapyshouldmaintaintheelasticityoftheskin,whichiscriticalforitsprotectivefunction.Forthemeasurementoftheskinelasticity,wemadeuseoftheprobeCutometerMPA580.Itpullstheskinintotheprobebyusingnegativevacuumpressure,andmeasurestheskindeformationbycomputersoftwarebeforeexpressingtheresuItinarbitraryunits.[]061

Usingtheprobesdescribedabove,wewereabletoquantifythechangeinbiophy’sicalindicesoftheskinbarrierduringthetreatmentofSDusingthemoisturizer.

Chapter2:MATERIALSANDMETHODS

2.1Patients

Amtalof98patientstookpartinthestudy,including52femalesand46males诵t11ameanageof45.5yearsold(range:15-83yearsold)andameandurationofSDof1.8years(range:0—13years).Thesubjectswerechosenbasedonthefollowinginclusioncriteria:

?ClinicalevidenceofSD,asdiagnosedbyadermatologist,basedonthe

andpruritus.Thepatientshadtypicalfeaturesoferythema,papules,scales

mild-moderateSDbasedontheclinicalfindings.

?Excellentcompliancetothestudyprotocolandself-applicationofthemoisturizertwicedailyduringtherequiredperiodoftime.

?Absenceofanyotherconcurrentsystemicortopicaltherapies.

2.2Studyprotocol

Patientsinvolvedin廿1estudywereinformedaboutthestudyandawriReninformedconsentWasobtained.ForeverypatientsufferingfromSD,theage,gendeLmodeofonsetofthediseaseandconcomitantmedicationswererecordedontheirarrival(DO).111eSDpatientsusedthemoisturizertwiceperday(everynightandmorningafterwashingtheirface)for4weeks.Theseverityofthelesionswasestimatedandscoredbyadermatologistandthepatients’self-assessmentwasalsorecordedonD0,D7,D14andD28.

Signsofskinbarrierfunctionlikesebumcontent,skinhydration,TEWL,pH,erythemaandmelanincontent,aswellaselasticitywerealsoassessedbydermatologists、^,imstandardcapacitancemeasurementsateachvisit.Being

andobjective,theCourageandKhazakamulti?probeadapternon-invasive,precise

MPA5systemwasusedforthispurpose.rnleprobeswereusedasfollows:

?sebumeterSM815forsebumcontent,

?comeometerCM825forskinbydration,

?tewameterTM300forTE、vL.

?skin—pH-meterPH905forskinpH,

?cutometerMPA580forskinelasticity,and

?mexameterMXl8formelaninanderythemacontent.

Thesitesexaminedweretheglabella,nasolabialfold(cheek)onthemost

involvedsideclinicallyandthechinsincethesearemostcommonlyaffectedareasin

thetemporo-mandibularjoint(TMJ)asaOUrpatients,aswellastheskinoverlying

contr01.Allsubjectswererequiredtowashtheirfaceproperlyusinganinertcleanser,andremaininactiveat20-22。C,andatarelativehumidityof55—60%foratleast30rainbeforemeasurementsweretaken.Themeasurementswerenotdoneunderanydirectlamplightordirectsunlight.

AllstudieswerecompletedbetweenthemonthsofMarch-May2012,correlating

andearlysummerinsouthernChina.ThestudyprotocolWasapprovedby、析也spring

theInstitutionalReviewBoardatXiangyaHospital,CentralSouthUniversity.Duringthe4-weekstreatmentperiod,theSDpatientswereinstructednottouseanyothermoisturizerordrugs,andtocomplybythestudyprotoc01.

2.3Efficacyandsafetyassessments

FourtypicalclinicalmanifestationsofSDinclude:erythema,scales,papuleandpruritus.Thesewerescorednumericallyfrom0to3ontheforehead/eyebrows,nasolabialfolds,perioralareas/chinandposterioraspectoftheears.

?O:absent,

?1:mild.

?2:moderate

?3:severe

Themaximumscoreforeachofelinicalmanifestationswas12(4×3)andforeachpatientwas48(4x3×4).EvaluationwasperformedonDO,D7,D14andD28.111epatients’self-assessment[bad,nochange,littleimprovement,improvement,majorimprovementandtotalcure]ofthetreatmentWasassessedontheD7,D14andD28,andeachtimeitwasscoredfrom0to5.

?O:bad.

?1:nochange,

?2:littleimprovement.

?3:improvement,

?4:majorimprovement.

?5:totalcure

Localsideeffectsofthemoisturizersuchastingling,burningsensation,painor

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