中图分类号
UDC
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:
学位论文版权使用授权书
本人了解中南大学有关保留、使用学位论文的规定,即:学校有权保留学位论文并根据国家或湖南省有关部门规定送交学位论文,允许学位论文被查阅和借阅;学校可以公布学位论文的全部或部分内容,可以采用复印、缩印或其它手段保存学位论文。同时授权中国科学技术信息研究所将本学位论文收录到《中国学位论文全文数据库》,并通过网络向社会公众提供信息服务。
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
a
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
a
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