’WPC ‡Sݤ÷1ÓcVĒS|®²åµ’ŚžbbķŠˆŗ&ŻdJßÖßfØäŽ”žbŅh6#?“Œ5€JÅK½QL—’[r(’0‚³Ų’Ÿ³b3ŪĒ ßČƝ¼×ōŌ¾źØŃA Ś_W{Y8.Ć|°åÓś„©ó I ŚÅ‚°‚¹v^9@—ņü}2»| ō'€H<™Č§_Fk“—”G_ /Ū5Ÿņ¾ĪŅ9²öÜzŃHę­Č =ŠŚƒ“ÉLIśn†°Ų°ā£Ū;Tyī“FJXæÅ'÷įčKUįDē'L/}2’”?„5’žæœ·+j\Ų±·M æėčVŗOüwXL‰÷Ąq7€TŲ›'éłMXD¶‹\’6Ś]2żŠŽĘ‚b‰} … žæn{ŒžÕ… ŗ£ōĘ ō€y”ĒGوLŁŚ”ŒšĪƒĆ¤Qō—ntĶ„+@½mJŖ¬É,OĻ&ģŃoJ’ ŽŃJ‘ėłRņ›1śŽŒū˜Ū›«w¤”Ųv/įzI9ŒsÄcŻĮb¤§2O ŅĖʋļwk }ĘsÕ*©B7ļüčšRŚ‸ÅaˆĮ <> ﺊ£]¦¤;„GĖßäVhŒāYŻšßbN¼½s*» źĻė…Ć5ęUNī %< 0(B jw@p#!° ŃU:Ż!'! 7!W )ē éļ"ģŲNÄ4Ę^ Śę mčU:’U:9Ęs9999999 0DAAA D+……………………………………… AY°Ę  0FĻ(ÖĆ9 Z ‹6Times New Roman RegularX($””’’H% £ æ¤ „ æ¦  § Ø D© Ŗ « E¬ ˜BIC7018P/ Library A–ś¦øø¦–ś0NgFLh,†r‰AZ‹"Arial Regular3|U¬ 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Š„#C°°’Xwøž’ž’ž’ž’ž’ž’ž’’’’’’’’’’’’’’’’’ž’ž’ž’ž’’’’’ž’ž’ž’ž’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’ž’ž’ž’ž’ž’ž’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’’³ØG%hŽe%ä’U‹’ĄĄĄ,ZżµAZ‹"Arial Regular,ZżµAZ‹"Arial RegularLevel 1Level 2Level 3Level 4Level 5 (3Æ$££Ż ƒ!ŻŻ  Ż'ČČČČdxd3 4#Mü’ << deUU…Level 1Level 2Level 3Level 4Level 5(n$––ņ ņ(Ś  Ś1Ś  Ś)ó óŻ ƒ!ŻŻ  ŻŌ_ŌŌ‡ X|ģXXXŌC:/Ō_ŌdmsoŌ_Ō/snore9.Ō_ŌwpdŌ_ŌŠ ° ŠĢMost€recent€update:€23€October,€1998,€3:00pmĢĢņ ņPHARMACOLOGIC€MANAGEMENT€OF€SNORING€BY€INTRA„ORALŠ H˜ ŠADMINISTRATION€(NON„NASAL)€OF€DIMETHYL€SULFONE€(DMSO2)ĢŌ#†XFHXX X|ģ+#ŌŌ‡ X|ģXXXFHŌó óĢSleep€disorders€arising€from€snoring€or€arousal€from€difficulty€in€breathing€due€to€upperĻairway€obstruction€(obstructive€sleep€apnea)€causally€related€to€snoring€affects€a€largeĻsegment€of€the€population€(Ō_ŌLugaresiŌ_Ō€et€al,€1989).€€This€patent€pertains€to€an€interventionĻagainst€snoring€by€introduction€of€a€water„based€solution€of€Dimethyl€sulfone€(DMSO2)Ļby€a€spray€onto€the€uvula,€soft€palate€and€proximal€tissues€in€the€oral€cavity.ĢŌ#†XFHXX X|ģƒ#ŌŌ‡ X|ģXXXFHŌĢņ ņThe€Mechanics€of€Snoringó óŠ jŗ  ŠĢThe€mouth€is€essentially€a€biological€wind€tunnel.€€The€Ō_ŌaerodymicŌ_Ō€principles€which€canĻexplain€snoring€were€worked€out€in€their€essentials€by€Bernoulli€in€the€17th€century€and€Ļdeveloped€continuously€since€then,€but€most€aggressively€since€the€late€19th€century€byĻphysicists€and€aeronautic€engineers.€ĢĢThe€mechanical€forces€operative€in€the€flight€of€a€bird,€a€glider€or€a€powered€aircraft€areĻthe€same€as€those€operating€in€the€mouth€during€breathing€that€causes€the€snore.€€BothĻare€concerned€with€the€aerodynamics€of€lift:€pressure€differentials,€drag,€laminar€flowĻand€turbulence€being€the€most€important€data€points.Ō#†XFHXX X|ģ#ŌŌ‡ X|ģXXXFHŌŠ l¼ ŠĢWhen€air€moves€over€any€surface,€it€changes€the€effects€of€air€pressure€that€impact€onĻthat€surface€compared€to€the€effects€of€a€calm€or€static€atmosphere€on€that€surface.€€€ĻThe€movement€of€air€over€a€surface,€when€confluent€and€laminar€ņņalwaysóó€€results€in€aŠ T Šlowering€of€atmospheric€pressure€impacting€that€surface.€€In€the€case€where€turbulentĻcurrents€arise,€such€as€vortical€currents,€there€can€be€fluctuating€increases€of€pressure.€ĻRecall€that€air€pressure€is€the€sum€result€of€billions€and€trillions€of€impacts€of€theĻgaseous€mixture€on€a€surface.€The€force€value€given€for€this€pressure€is€measured€byĻmeans€of€a€small€diameter€Ō_ŌcollumnŌ_Ō€of€mercury€inverted€in€a€bath€which€is€open€to€theĻatmosphere.€€At€sea€level,€the€atmosphere€impresses€on€a€static€body€a€force€of€760ĻmmHg/si.Ō#†XFHXX X|ģ£#ŌŌ‡ X|ģXXXFHŌ€€By€virtue€of€the€movement€of€air€over€a€surface€there€are€less€impacts€perŠ P# " Šunit€of€area.€€This€equates€to€lower€pressure€on€that€side.ĢĢThe€tongue,€uvula€and€bifurcating€flaps€of€skin€forming€the€soft€palate€and€whichĻseparate€the€sinal€cavities€from€the€oral€cavity€approximate€the€profile€of€a€wing.€ĻAssuming€that€air€pressure€is€lowered€above€the€tongue,€for€example,€the€air€pressureĻbelow€the€tongue€will€now€act€without€a€counteracting€force,€and€thereby€the€tongue€willĻrealize€a€differential€on€one€side€and€the€tongue€will€move€in€the€direction€of€the€lowerĻpressure.€€This€is€lift.€€This€effect€is€especially€pronounced€and€observable€in€the€softĻpalate€and€uvula,€and€in€some€cases€the€vocal€chords€and€related€tissues€themselves.€ĻThe€same€basic€concept€explains€the€movement€of€weather€patterns:€from€a€highĻpressure€zone€into€a€low€pressure€zone.Š 2-‚(- ŠŌ_Ō‡In€the€normal€mouth,€the€act€of€breathing€actually€should€enlarge€the€cross€section€ofĻthe€oral€cavity,€€making€breathing€easier,€not€more€difficult,€and€the€ability€to€inspireĻfresh€oxygen,€and€dump€CO2€can€proceed€uninhibited.€€There€are€three€fundementalĻparameters€to€consider€in€the€complications€of€breathing€that€result€in€snoring:ĢĢ1)€increased€surface€resistance,Ģ2)€the€controlling€muscles€become€exhausted€and€relax,€causing€constriction,Ģor,Ģ3)€inordinant€swelling€altering€the€soft„tissue€conformation,ĢŌ#†X…ĄXX X³“§ #ŌŌ‡ X³“XXX…ĄŌĢUnder€these€conditions,€alone€or€in€combination,€lift€characteristics€can€change,€and€likeĻa€flag€in€the€wind,€the€uvula€and€surronding€leading€edges€of€the€soft„palate€can€result€inĻflapping.€€Sometimes€these€alterations€can€reach€a€very€high€rate€of€vibration.€€EvenĻwith€a€comparatively€massive€organ€as€the€vocal€or€oral€tissues,€up€to€1000€vibrationsĻper€second€have€been€measured€(€)€reaching€volumes€comparable€to€a€jack„hammer€(€).ĢĢAlthough€all€mouths€follow€the€same€general€plan,Ō#†X…ĄXX X³“v#ŌŌ‡ X³“XXX…ĄŌ€each€mouth€is€essenially€unique,€andŠ ` Šas€of€yet,€no€predictive€standard€has€stood€the€test€of€clinical€application€in€judgingĻwhether€one€will€be€a€snorer€or€not.€€And€not€all€snoring€can€be€taken€care€of€by€anyĻsingle€therapeutic€application.ĢĢFactors€affect€surface€resistance€and€that€impinge€on€and€may€play€more€or€lessĻimportant€roles€muscle€tone€and€states€of€tissue€shape€are€hydration€and€texture,Ļfundemental€cavity€conformation,€states€of€turgor,€tumescence€and€relative€flaccidity€ofĻthe€invovled€tissues.ĢĢA€wet€mouth€offers€less€resistance€to€air€flow€than€a€dry€mouth.ĢTexture€of€the€mouth,€whether€wet€or€dry€is€a€distinct€factor,€and€can€vary€depending€on:ĢĢ1)€genetic€disposition,Ģ2)€nutritional€states,Ģ3)€dehydration,Ģ4)€infectious€and/or€parasitic€vectors,Ģ5)€mechanical€injury,Ģ6)€dentition,Ģ7)€hygeine.ĢĢFundemental€cavity€conformation€as€conceived€in€this€paper,€is€a€genetic€conditionĻpertaining€to€the€bone€substrate,€muscle€and€tendon€disposition€and€soft€tissue€overlay.ĻIt€is€not€known€to€what€extent€such€genetic€dispositions€contribute€to€the€overallĻincidence€of€disease,€butŌ#†X…ĄXX X³“£#ŌŌ‡ X³“XXX…ĄŌ€in€some€people€the€received€or€heritable€characteristics€mayŠ  (š#( Šbe€such€as€to€require€adjustment€surgically€or€mechanically€for€any€significant€beneficialĻeffect€towards€amelioration€of€snoring.Ō#†X…ĄXX X³“L#ŌŌ‡ X³“XXX…ĄŌ€€Since€genetic€issues€and€surgical€andŠ l*¼%* Šmechanical€methods€of€intervention€lie€outside€the€domain€of€the€claims€of€this€patent,Ļthey€will€not€be€discussed€in€any€further€detail.ĢŠ -n(- ŠNutritional€issues,€mechanical€injury,€dentition€and€hygeine€will€not€be€discussed€to€anyĻextent€herein.€€However,€hydration€and€muscle€tone€are€pertinent€to€the€claims€of€thisĻpatent.ĢĢIn€aerodynamics,€and€hydrodynamics,€when€we€wish€to€increase€the€velocity€of€aĻstream€of€air€or€water,€we€constrict,€narrow€or€decrease€the€cross„section€or€diameter€ofĻthe€wind€tunnel,€nossle€or€what€have€you.€€This€method€of€increasing€velocity€withoutĻaltering€source€pressure€or€medium€volume€is€called€the€Venturi€effect.€€The€volume€ofĻair€remains€constant,€but€the€rate€of€flow€increases,€and€when€you€have€a€significantĻrate€of€increase,€you€also€increase€the€possibility€of€lift€with€itššs€various€sequalae€ofĻš šflappingšš€due€to€turbulence,€and€the€resultant€snore.Ō#†X…ĄXX X³“b#ŌŌ‡ X³“XXX…ĄŌŠ ¬ ü  ŠĢTurgor€of€tissues€affects€surface€texture,€but€perhaps€most€importantly,€the€mutableĻstates€of€conformation€of€the€oral€cavity.€€Normal€turgor€is€what€we€may€see€in€a€healthyĻbabyššs€mouth.€€In€the€elderly,€a€preponderance€of€whom€are€usually€dehydratedĻ(Batmangheldji,€1996),€we€most€often€see€flaccid,€parchment€thin€tissues.€Turgor€isĻnormal,€but€there€is€a€condition€of€swelling€that€we€will€term€tumescence,€because€thisĻterm€is€more€closely€related€to€the€Latin€word€for€swelling:€tumor.€Tumescence€canĻresult€from€various€conditions.Ō#†X…ĄXX X³“~#ŌŌ‡ X³“XXX…ĄŌ€€There€may€be€inflammatory€effects€due€to€local€or€distalŠ Ü, Šinjury€with€subsequent€increased€vasodilator€effects€due€to€prostaglandin€secretion;Ļsystemic€loading€of€histamine,€etc.€This€lies€outside€the€domain€of€claims€for€this€patent,Ļand€will€not€be€discussed€in€any€further€detail.ĢŌ#†X…ĄXX X³“ō#ŌŌ‡ X³“XXX…ĄŌĢIn€some€cases€swelling€can€be€non„inflammatory€and€due€rather€to€a€laxation€of€theĻmuscles€controlling€blood€volume€through€the€arterioles€and€capillaries€feeding€theĻtissues,€by€which€means€the€oral€cavity€becomes€inordinantly€constricted.ĢĢņ ņPhysical€Causesó óŠ ņB ŠĢDesfonds€(1998)€and€his€group€showed€that€part€of€the€airway€resistance€arises€strictlyĻfrom€anatomical€effects€that€pertain€to€position.€€While€individuals€show€higher€airwayĻresistance€in€the€reclining€position,€regardless€if€they€are€snorers€or€nonsnorersŌ#†X…ĄXX X³“g#ŌŌ‡ X³“XXX…ĄŌ,€snorersŠ  ß Šespecially€have€higher€than€normal€nasal€airway€resistance€in€the€supine€positionŌ#†X…ĄXX X³“É!#ŌŌ‡ X³“XXX…ĄŌ.Š u!Å  ŠŌ#†X…ĄXX X³“z"#ŌŌ‡ X³“XXX…ĄŌĢSleep€induced€apnea€is€distinguished€from€obstructive€or€peripheral€apnea€in€that€theĻlatter€condition€is€due€either€to€obstruction€or€inadequate€respiratory€muscleĻactivity.(PDR„Med.€Dict,€1998).€€We€will€not€discuss€apneas,€but€the€same€condition€isĻrelevant€in€snoring.ĢĢŌ#†X…ĄXX X³“Ņ"#ŌŌ‡ X³“XXX…ĄŌņ ņTreatments€of€snoringó óŠ æ'#' ŠĢCurrently€methods€of€intervention€against€snoring,€as€well€as€apneas€are€comprisedĻprimarilly€in€surgical€or€mechanical€devices€to€insure€jaw€position€and€tongue€position,Ļmouth€closure,€or€enlargement€of€cross-section€of€the€nasal€pharyngeal€cavitiesĻincluding€tonsillectomy€and€uvulectomy.€€Anti„inflammatories,€decongestants€orĻantihistamines€have€no€positive€effect€on€snoring,€and€often€exacerbate€it€(Jacob,€1996Š (-x(- Špatent,€#5,569,679).Ō#†X…ĄXX X³“'$#Ōń¢ ńŌ‡ X³“XXX…ĄŌń¢ ńŠ ° ŠĢń£ ńŌ‡X³“XXX…ĄŌń£ ńNose€strips€have€been€looked€at€adjunctively€and€alone,€and€found€to€have€noŠ Ļ Šsignificant€affect€on€snoring,€whatever€else€may€be€said€for€their€role€as€an€aid€to€freerĻbreathing€during€the€conscious€state.ĢĢIn€a€prior€patent,€it€was€described€that€Jacob€and€associates€performed€a€trial€studyĻń¦ ńagainst€snoring€by€ńž ńinńž ńń  ńtranasal€spray€ń  ńń¦ ńusing€a€16%€solution€of€Dimethylń£ ńŌ#†X…ĄXXX³“©&#Ōń£ ńń„ ńŌ‡X³“XXX…ĄŌń„ ń€Sulfoneń„ ńŌ#†X…ĄXXX³“š(#Ōń„ ńń¤ ń€ń¤ ńŌ‡ X³“XXX…ĄŌń§ ńas€the€sole€ń§ ńńØ ńpharmacologic€ńØ ńinterventionń© ń€ń© ńńŖ ńagainst€snoringńŖ ńń« ńńŖ ń€by€intranasal€spray€ńŖ ńń« ńń¬ ń€ń¬ ńńŖ ńŌ#†X…ĄXX X³“ž(#ŌŌ‡ X³“XXX…ĄŌńŖ ń.€€InŠ ż M Šthe€current€invention€the€claim€covers€only€and€onto€the€soft€palate€and€uvulaĻŌ#†X…ĄXX X³“×)#ŌŌ‡ X³“XXX…ĄŌintervention€and€carried€out€this€study€for€a€period€of€one€month.€€Of€(12€patients€with€8Š Ģ   Šrelief€of€snoring,€occured€in€the€first€2€evenings,€using€the€nasal€spray€See€patent€1;€2/3Ļexperienced€relief€10€patientsTable€1€summarizes€these€findings.ĢŌ#†X…ĄXX X³“‡*#ŌŌ‡ X³“XXX…ĄŌņ ņĢŌ#†X…ĄXX X³“Õ+#ŌŌ‡ X³“XXX…ĄŌBibliographyó óŠ i¹  ŠĢCohn€M,€Hesla€PE,€Kiel€M,€Nay€KN.€€Vibration€frequency€of€snoring€in€obstructive€sleepĻapnea€syndrome€(Abstract).€€Chest€1986;€89(suppl):529.ĢDesfonds€P,€Planes€C,€Fuhrman€C,€Foucher€A,€and€Raffestin€B.€Nasal€Resistance€inĻSnorers€with€or€without€Sleep€Apnea:€Effect€of€Posture€and€Nasal€Ventilation€withĻContinuous€Positive€Airway€Pressure.€Sleep,€1998;€21(6):625„632.ĢHoffstein€V,€Is€snoring€dangerous€to€your€health?€[Review][34€refs],€Sleep.€€19(6):506„¼16,€1996€July.ĢĢLavie€L,€Perlman€A,€Pillar€G,€Lavie€P.€Plasma€Homocysteine€levels€in€obstructive€sleepĻapnea,€Abstract€of€paper€delivered€at:€Associated€Professional€Sleep€Societies,€12ĻAnnual€Meeting,€June€18„23,€1998,€New€Orleans,€Louisiana;€published€in:€Sleep,Ļ21(Supplement):240(160.k1).ĢLezoff€A,€Haight€JS,€Hoffstein€V.€Reversible€Obstructive€sleep€apnea€caused€byĻoccupational€exposure€to€guar€gum€dust.€Am€Rev€Respir€Dis€1986;€133:935„936.ĢLugaresi€et€al,€Snoring:€Pathogenic,€Clinical€and€Therapeutic€Aspects€(1989);€In:ĻPrinciples€and€Practice€of€Sleep€Medicine€(Kryger€et€al,€Eds.)pp:€494„500.ĢLugaresi€E€and€Plazzi€G.€Heavy€Snorer€Disease:€from€snoring€to€sleep€apnea€syndromeĻ„„€an€overview.(Respiration,€1997,€64€Suppl€1:11-14;€[Review,€15€references].ĢMcNichols€WT,€Tarlo€S,€Colle€P.€Obstructive€apneas€during€sleep€in€patients€withĻseasonal€allergic€rhinitis.€Am€Rev€Respir€Dis€1982;€126:625„628.ĢSinclair€AS,€Roach€MR.€€Effect€of€vibration€on€isolated€dog€bronchi.€€J€Appl€PhysiolĻ1975;€38:780„785.ĢTelescu€D,€Medical€Hypotheses€(1998)€50,€125„129.ĢUlfberg€J.:€Snoring€and€headache:€an€important€association€[letter;€comment].€ĻComment€on:€Arch€Neurol€1994€Sep;51(9):937„42;€Arch€Neurol€52(11):1043,€1995€Nov.ĢUlfberg€J,€Carter€N,€Talback€M,€and€Edling€C.€Occupational€exposure€to€organicĻsolvents€and€sleep„disordered€breathing.€Neuroepidemiology,€1997€16(6):317„326.ĢZwillich€CW,€Pickett€C,€Hanson€FN,€et€al.€Disturbed€sleep€and€prolonged€apnea€duringĻnasal€obstruction€in€normal€men.€Am€Rev.€Respir€Dis€1981;€124:158„160ĢĢŌ#†X…ĄXX X³“,#Ō„„„„Š .-~(- ЇNotes:ĢĢKakitsuba€N.€€Sadaoka€T,€Kanai€R,€Fujiwara€Y,€and€Takahashi€H>€Peculiar€snoring€in€patientsĻwith€multiple€system€atrophy:€its€sound€source,€acoustic€characteristics,€and€diagnosticĻsignificance.€€An€Otol€Rhin€&€Laryng.€€106(5):380„4,€1997€May.ĢĢSome€forms€of€snoring€are€due€to€abductor€paralysis€of€the€vocal€folds€as€occurs€in€MultipleĻSystem€Atrophy€(MSA).Ģ„„„„„„„„ĢStrike€sentences:ĢĢŌ‡ X³“XXX…ĄŌObstructive€effects€due€to€inflammation€can€represent€an€end„point€in€a€chain€ofŠ ³  Šreactions€to€organic€solvents,€organo-€and€chloro-€phosphates,€heavy€metalĻparticulates,€some€inert€particulates€(some€forms€of€asbestos),€pollens€and€plantĻaerosols,€particulates€(especially€saw€dust€of€dried€resinous€woods)€and€food€derivedĻallergens€(Ulfberg€et€al.,€1997).€ĢŌ% € ŌŌ#†X…ĄXX X³“‘5#ŌĢĢŌ‡ X³“XXX…ĄŌSleep€induced€apnea€may€arise€from€the€lack€of€activity€in€the€respiratory€centers;€whileŠ S Šperipheral€apnea€may€arise€from€lack€of€effective€muscle€response€to€signals.Ō#†X…ĄXX X³“]7#Ō