`
`IIPOCIDECCI/IOHAHLHOTO OBPABOBAHI/IH
`
`«BEIII/IKOHYKCKAH FOCVILAPCTBEHHAFI AKAILEMI/Ifl (DI/IBI/IT-IECKOI71
`
`KVHBTYPBI I/I CHOPTA»
`
`Ha npaBax pyxonncn
`\W/D
`
`BEJDIEB AHJIPEFI l‘EHHAlIBEBI/Iq
`
`BJII/IHHI/IE MAFHKTHOFI CTI/IMYJIHIII/II/I HA CI/IJIOBLIE
`
`BO3MOXCHOCTI/I CKEJIETHLIX MLIIIIH
`
`03.03.01 —- (bum/1011011451-
`
`flHCCBpTaHI/Ifl Ha COHCKaHI/Ie yquof/i CTCI'IeHH
`
`Karim/mam GKOHOFI/I‘IBCKI/IX HayK
`
`Hay‘iHLIfi pyKOBOlIPITeJIB
`
`,IIOKTOp 6nonomqecmx HayK,
`
`npocbeccop Fopozmmes P.M.
`
`Allergan, EX1083
`
`

`

`FHABA 1. OBBOP Ifl/ITEPATYPLI ......................................................................... 9
`1.1.
`06111251 xapamepncmxa MbIIIIC‘iHOfi 01mm .................................................. 9
`1.2. MCTOIIBI paBBI/ITI/DI MLImetIHoi/‘I 0mm .........................I................................... 18
`1.3. MaFHHTHafi CTHMymme B chnenonaflmx qenoaexa..................................27
`FHABA 2. OPI‘AHI/IBALII/IH I/I METOIILI I/ICCIIElIOBAHI/ISI.........................35
`2.1. KOHTHHreHT PI opraHnséuua Hccnenoaanm ................................................. 35
`2.2. MBTOJILI Hccnenoaanm ................................................................................. 36
`
`
`
`
`2.3. chomm perucrpaunn 3nempoxunorpa¢mecmx napamexrpon B0 BpeMx
`upOBenean 3KcnepnmeHTa..................................................................................40
`2.4. MSTOILBI maTeMaTqucxofi CTamchH.........................................................42
`FHABA 3. OCVOBEHHOCTI/I BLI3BAEJHI>IX MLILUELIHBIX OTBETOB HPI/I
`MAFHI/H‘HOI/I I/I BJTEKTPI/F-IECKOI/I CTI/IMVJIfllfl/H/I
`IIEPI/ICDEPI/ILIECKOI‘O HEPBA ...........................................................................43
`3.1. H3MeHeI-IPDI napamerpoa BBIBBaHHbIX MLImeqHLIX enema npn yBenmIeHI/m
`CPUILI OJIHOKpaTHofi MarHHTHofi u sneKTpnqecxofi CTKMyJIflIII/II/I n. tibialis ........44
`3.2. 1/13meHeHm1 Benntmnm BpamaTeJIbHoro MOMeHTa npn HOBBIIIIBHI/II/I qac
`n HHTechBHocm pn'rMImecmx cmmynxmdonflmx Bosneficranfi .....................
`3.3. annme MaanTHofi crumymmun Ha PIMIIyJIBCHyIO aKTIrIBHOCTI: OTJICJIBHBIX58
`mamaTenLHLIx emumu m. gastrocnemius ............................................................
`FHABA 4. BJII/IflHI/IE MAFHI’ITHOCTI/IMYJIHIMOEH—IOFI TPEHI/IPOBKI/I
`HA CI/UIOBHE BO3MO>KHOCTK CKEIIETHLIX MLIUJII
`4.1. I/IsmeHeHHe IIOKa3aTenefi Mblflleqflofi cmm npn MaanTHofi cmmynalmu
`MLIIIIIJ; .................................................................................................................... 63
`
`4.2. flHHaMHKa Mmmeqfiofi cmm nocne npexpamenm
`MaanTHocmMynmmonHofi TpCHHpOBKK ............................................................72
`FHABA 5. OBCYXCJIEHI/IE PEBVJILTATOB ...................................................... 80
`BBIBOILH ................................................................................................................ 89
`HPAKTI/ILIECKI/IE PEKOMEHlIALII/II/I ...............................................................91
`CIII/ICOK III/ITEPATVPBI ........................'.............................................................92
`
`Allergan, EX1083
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`ATCD — anenosnmpmbocdmpnax manna”
`
`BMO — BLISBaHHLIfi MOTopHLIi/‘I OTBeT
`
`LLB — anraTenLHaa emmuua
`
`MBM — Maxchaanmfi BpaIIIaTeJ'IBI-Iblfi MOMCHT
`
`ME ~ MOTOHefipOHHLIfi nyn
`
`MHC — Maxcmanmax npomBonLHaa anIa
`
`MC — MaerHasI CTI/IMYIIXHPIH
`
`PHK — pKGOHyKJIeHHOBafl mcnm‘a
`
`CTF — COMaTOTpongIfi ropMOH
`
`T —— TeCJILI
`
`LIHC -— IICHTpaJIBHaH HepBHax cucurema
`
`3MP - SHBKTpOMHOI'paMMa
`
`BMC — aneKTpOMHOCTnmynxunx
`
`3C —— aneKTmeecKax CTHMmenmI
`
`GM — HKpOHoxcHaz Mblnma
`
`SOL —- KaM6aJIOBHnHa5I Mblfllua
`
`TA — nepenwm Gonbmefiepuonafi MBIIIILIa
`
`
`
`Allergan, EX1083
`
`

`

`Amanwocn nccnenonanm. Cnnosme
`
`BoamoxcHocm qenoneKa
`
`noaBonmoT oxaBLIBaTL LICJIGHaIIpaBJIeHHOé 13111451131118 Ha oxpyxcalomyro cpeny PI
`
`Gondin et al., 2014).
`
`1.18an171
`
`psm I/ICCJIBIIOBaHI/Ifi
`
`cneHHaJmQTOB
`OBBIX Bo3Mo>1<HOCTefi quIOBeKa (VIII.
`
`IIOCBHHIEH
`
`KeneTHHx 1145111111 HOCpeJICTBOM 14x 3n
`
`oGecneanaTL anan'raumo opraHnsma Henonexa K pa3nanLIM YCJIOBHHM ero
`mnsnenemenbuocm Ha Bcex
`3Tanax
`IIOCTHaTaJIBHOI‘O 0HTOI‘BH63a
`BOp06BeB, 1989; ML. Foss, SJ. Keteyian, 2008; AB. CaMCOHOBa, 2011; AA.
`14). 00060 Baxmoe 3Haquu8 CI/IJIOBBIC BO3M0>KH00TH I/IMEIOT B
`Ilemaoxoxa, 20
`.
`cnopTHBHofi nezTeJILHocm, Tax KaK pCBYJIBTaTLI B pane 131mm; cnop'ra BO MHOI‘OM
`onpenenmoma CI/UIOBLIMI/I cnocofiHocmMH cnopTcmerB (B.M. Bannopcxnfi,
`2009; AM. Herp86a PI up, 2011).
`sxcnepnmemanbnmfi
`K HaCToxmeMy BpeMeHH Haxonnea 06prHBIfi
`MaTepHaJI 06 atbtbeKmBHocn/I paanqHLIx MeTozLOB H nonxonoa K pawl/1171410
`CPIJIOBBIX cnoco6nocren qenosexa (BC. UleumaH K 11p., 2006; M.H. Stone et al.,
`2007; BE. Hyper/men, 2011; 0.11. BI/IHOI’palIOBa H lip, 2014). I/IMeIOTcx CBCIIBHPISI
`0 (bK3I/IOJIOFPI‘ICCKI/IX M6X3HK3MaX, nexaumx B OCHOBC pa3BHTKH CI’UILI CKeJIeTI-IBIX
`Mam (RM Enoka, 1988;10..B Kopm‘HHa, 2003; PM. roponuuqea 2005; J
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`HeTpazmuHOHHbe MCTOILOB HOBLImeHm can
`1979; BY.
`(DBLIOTOBa, 2010; G. Attene 8t al., 2014), CpClII/I KOTOpLIX
`
`PaTOB,
`mar
`1c passm‘mo 8mm
`'HaIrI60JIee BCCCTOpOHHe oanaHLI Me'ronmecme nonxo
`
`empocmMymmH B coc'roslmm noxox n
`
`
`n8cHHKOB, 1977; A..A HHKOHaeB, 1999; J. Gondin et a1, 2005).
`'
`,3neKTpocmMyJImI/IOHH851 TpeHHpOBKa Mmmequfi 8mm nMeeT HeKOTOpBIC
`
`CBHBaHHBIe c IIOHBJIBHI/ICM 6OHBBBIX omymelmfi n macxomcbopTa,
`KTqueCKoro pasnpaxcemm. Tame
`
`Qa, ofioMépHo BBI3LIBaCMbIX Bo3nefi0TBneM 3H6
`
`
`
`Allergan, EX1083
`
`

`

`aneKTquecxofi cmmmem/m. B CBHBI/I c 3THM 61:11:11 HpOBelLeHBI nccnenoaanm no
`n3ytxe11mo 13111151111111 oncremamqecxofi maanTHofi CTnMynxunn 'cxeneTme M1:111111
`B cocmmmn IIOKOfl Ha IIpOXBJIeHI/Ie cunesmx cnocoGHocrefi y 3,110po131:1x 1101101151);
`1110116171
`(P.M. FoponHmieB 11 11p., 2007),, KOTOpBIe noxazam/I edgtbeKTHBHOCTI:
`MaerHocmMymanHofi TpeHPIpOBKH Ha cpmy cxene'mmx 1113111111. HpH TaKofi
`TpBHHpOBKe
`HBOGXOJIPIMO
`BOBflefiCTBOBaTB Ha MBIIIIHy
`O‘ICHI: MOIHHBIMK
`CTKMyIIaMPI, HO TCXHI/I‘ICCKHC
`BOBMOXCHOCTI/I
`JIEDKC HOBefiIIlI/IX MaFHI/ITHBIX
`CTHMYJ'ISITOPOB
`CHOCO6HLI
`I‘BHepI/IpOBaTB
`TOJILKO
`OHPCJIBJ'IBHHOC
`HHTechBHLIX CTHMyHOB. C yquOM 31010 O6CT051T6IIBCTBa 11 éHamrIsa CBeJIeHPIfi
`JIHTepaT'ypBI npeJICTaBJmIIOCI: OHpaBJlaHHBIM 1/13?me BosMomHocru nsMeHeHm
`CHJIOBLIX cnocoGHOCTefi M1:111111 HOCpeflCTBOM 601166 cna6oro no HHTCHCHBHOCTH
`
`
`
`
`
`
`
`
`
`
`
`
`
`'MaI'HI’ITHOI‘O BO3flefiCTBKfi Ha MBIUIHH-aI'OHKCTLI
`
`
`* HCHOCPBACTBBHHOI‘O BBIIIOJIHBHI/Ifl.
`Ofibem‘ nccnenonannsl -— MexaHHSMLI 13111151111151 MarHHTHofi cmmynfiuun
`
`
`7115qu 11a 11x (byHmHOHaJILHLIe cnoficma.
`IIpenmeT HOCJIBIIOBaHflfl —' ,IIHHaMHKa CHJ'IOBBIX BOBMOXCHOCTEi/i MBIIHH HpI/I
`
`JIBI/DKBHI/IH B 11130116006 CFO
`
`Mama, BBIBBIBaIOHIaSI axmaaumo nonoanTenLme llBI/II‘aTEJIBHBIX’eIIPIHI/IH, GyneT
`
`paGOTLI 3am1oqana01: B mayqemm BosMoxcHOCTefi HOBBIHICHPIH
`*V-Ilem:
`311111311110111 0111151 HoopeJlCTBOM puTMHtIecxofi marHHTHofi CTnMynquH M1:111111 Ha
`
`
`
`
`
`ocoGeHHocm pe¢1neKTopHLIx MLImeqHLIX
`fBLISIBI/ITI:
`1:11x Hanochoi/‘I Ha neanequecmi/i HepB onnoxpamon MarHHTHofi
`
`1‘z’1fip‘213m/1q110171 HHTBHCPIBHOCTI/I.
`
`Allergan, EX1083
`
`

`

`paBflI/IanOHIBfiCH HO ‘IaCTOTe III HHTeHCI/IBHOCTH CTI/IMyJIOB, Ha CHJIOBLIB MLIHIC‘IHBIB
`
`cnoco6Hocm.
`némeHeHI/Ifi Mmmeqnofi
`OCO66HHOCTK
`3. Onpenenm‘b
`BosnefiCTBnH MarHHTHofi n aneKTqueCKofi CTKMynflum/I c uenmo pa3pa60TKH
`OHTI/IMEUIBHOI‘O pexcha MaFHPITHOCTI/IMYJIHIIPIOHHOfi TpeHHpOBKI/I
`JIJISI paBBHTI/IH
`
`cpmoamx cnoco6nocrefi MBIIIIIJ; ronenu.
`qumBeIca HOIL
`4. MCCJICLIOBaTI:
`IIIBMeHeHI/Ie
`CPIIIOBBIX cnocoGHocrefi
`BJII/IHHPICM Kypca pnmmecxofi mammuofi cmmynxnnu, HaHochOfi Ha MBIUIIIBI
`
`PI
`
`HHTCHCHBHOCTl/I
`
`‘IBM l'IpH 3J16KTpI/IIICCKOM
`nncxom¢opmmx
`
`HEHOCPBHCTBeHI—IO B X0116 PIX COKanIEI-IPISI.
`Haytman Honnsua. B pa60Te nonyHeHLI HOBBIC 0138116111151 06 H3MeHeHnK
`pedpneKTopHofi BoafiynnMocm MOTOHefipOHOB CHHHHOFO Mo3ra HpPI yBGJIPI‘IeHIrII/I
`KHTCHCHBHOCTH OILHO
`KpaTHofi marHHTHofi 01‘mean nepmbepmec
`Hue omem, Busbmaemue
`
`
`
`
`
`
`
`
`
`
`
`
`HoxasaHo, qTo maKcnmaanme pefbnex'ropflme Mbnneq
`
`BBICOKOPIHTCHCI/IBHBIM MaFHI/ITHBIM BOBJlefiCTBI/IGM,
`JIOCTHFaIOTCH I’IpI/I MCHBHICM
`
`
`HpeBBIHIeHPIPI nopora, qu
`HepBa.
`
`nepmbepI/Iqecmro »_
`BpaHIaTeIILHOI‘O MOMCHTa
`
`mmmecxoro marmamoro 1303
`
`III B T0 >I<e BpeMH OTCYTCTBI/Ie GoneBHx H
`
`‘ aSILanCCHI/II/I
`mynos. Bnemee yCTaHOBneHo,
`
`“CUIYIIIBHKI/I B YCIIOBI/ISIX HaHeceHm mammnmx CTPI
`T01 HfiTHa/CIHaTI/IIIHCBHBII/I 1(pr MaFHHTHOPI CTI’IMYJUIHI/IPI CKCJICTHBIX MBIIIIII,
`
`QOHC PIX HpOI/I3BOJIBHOI‘O COKpaIlIeHI/Ifl, IIOBBIIIIaeT CKIIOBBIC
`
`OCOfiHOCTI/I MLIIIJII, 0Tpa>1<a10nmecsx B npnpocre MaKCHMaJIBHOFO cnnoaoro
`
`HHI’I MOHIHOCTH HPICXOMIIICI‘O npafiBa Ha
`
`saxonomepHme
`OHPCZICIIBHLI
`CHI’IHHOI‘O MOBI‘a.
`CTPOB SHCKTpI/I‘ICCKOI’I aKTHBHOCTI/I MBIHIII, nemaume B OCHOBB HOBBIIIICHI/IH
`
`K3115 Kxc Kpamenm B pezynLTaTe MarHI/ITHOCTPIMyIIflIII/IOHHOfi TpeHHpOBKH.
`6px ‘anecxan 3Ha‘fllMOCTb. HOJIyquHBIe B pa60Te JIaHHBIe pacumpmo'r
`
`hgte upenCTaBnerm o Mexaflnamax BJII/IHHI/IX BLICOKOHHTechBHoro
`
`BBISIBJ'IGHO meHLmee
`m1
`qaCTOTLI
`
`IIOBBIHICH
`HpId
`RCHCTBI/DI Ha MLIIIIHBI,
`
`
`
`Allergan, EX1083
`
`

`

`TpeanOBKH Mme LIOI'IOJ'IHHCT cnemp HeTpallYIIII/IOHHBIX MeTOlIHK mm pasBHTwi
`
`,[IBHFaTCJIBHLIX CHOCOGHOCTCf/i 1IeJIOEeKa. MaanTHasx CTI/IMyJISIIIPISI Mme M0)I(eT
`
`6LITL
`
`PICIIOJIBBOBaHa
`
`B KJIHHquCKofi HpaKTHKe
`
`npn
`
`pea6HHHTaIIKOHHOM
`
`BOCCTaHOBIIeHHH anraTenLHle (bymumi’i HaHHeHTOB nocne ‘ nonpequeHI/m H
`3a6oneBaHni71 CHHHHOFO Mosra H CKCJ’ICTHBIX MLIHm. HOJIY‘IBHHBIC JIaHHBIe o6
`
`aKTIrIBHOOTI/I MLImu-amHHcmB
`
`B
`
`npouecce
`
`MLImequfi
`
`CPIJIBI
`
`non
`
`MBIIIIH KMCIOT 3Ha‘ICHHe
`211151
`paSBI/ITI/Ifl TeopeTqucmx npencmanennfi O
`(baKTopax, oupenemnomnx 3¢®eKTHBHocTL paanqHLIx no npnpone BHeman
`CTPIMyJISILII/IOHHBIX Bosneficrnufi Ha HepBHo—MLImeqHLIfi annapa'r quIOBeKa.
`flpamnqecxan anaqnmocTL. Paspa60TaHHLIfi Merom/Iqecxnfi nonxop;
`noaLxmeHwI MLImequfi
`0mm HOCpelICTBOM MamHTHoCmmynxunonHofi
`
`
`
`
`
`
`
`
`
`
`
`
`PIBMeHeHI/II/I petbneKTopHLIx MBIIHC‘IHBIX 0TBeTOB H cmnoaoro BpamaTenLHoro
`
`MOMeHTa npu yBeaneHnH CHJILI H qaCTOTLI maanHofi
`I/I aneKTpnqecxofi
`
`cmmynxunn nepmbepnqecxoro HepBa PI “cam/Ix Mme MOXCHO flpKMeHflTB 11pm
`
`*Monennpoaafiun
`HaIIpaBJIeI-IHOI‘O
`BO3H6fiCTBHfl
`01411013le
`TpBHHpOBO‘II-ILIX
`
`
`OCHOBHI-Je HOJIODKCHHH, BblHOCl/IMBIC Ha 3aum'ry:
`1.
`HOCTaKTHBaIIPIOHHBIfi 3cp¢eKL BLIBLIBaeMLIfi namanuamnneanofi
`
`
`
`Lkmpuqecxofi
`
`KénManLHoro ycnmm.
`
`VBenmeHHe
`
`
`'"Hocmmynxunomofi TpBHPIpOBKPI Mme conpoaomnaeTca HBMeHeHPIeM
`LTOpHofi
`8036yJII/IMOCTK MoronefipOHHLIx
`I'IyJIOB,
`06ecneananmm<
`
`
`"MaKCI/IMaJIBHaSI
`
`
`
`JIHeHHB )IBYIFaTeJIBHOI‘O neficmm.
`
`aMHJII/ITlea pecpneKTopHLIx MLImetIHLIX OTBCTOB,
`
`LIX BBICOKOHHTBHCHBHOfi marHHTHofi cmMymunefi n aneKTpnqecKnM
`M nepn¢epp1qecxoro HepBa, nocmnepHo He pa3nmaeTcx, qTo
`
`Allergan, EX1083
`
`

`

`a¢®epeHTH3m 11
`
`3cp¢epeHTHLIX HepBme
`
`BOJIOKOH an 0601111 Bunax
`
`
`CTI/IMyJIfiLII/IOHHOI‘O BosnefiCTBKa.
`
`Anpoéaunn pafioTbl. Ho MaTepnahaM nnccepraunn 0ny6nm<03aHo 9
`
`He‘iaTI-IBIX p360'1‘, B TOM 7‘II/ICJIB 2 CTaTBI/I wB )KYPHaJIaX, BXOIIHHII/IX B nepequL
`
`BCIIYIIII/IX pEIleHBPIpyeMBIX Haqu-IBIX )KypI-IaJIOB PI H3LI3HI/Ifi, pCKOMeI-IJIOBaI-IHBIX
`
`BAK MHHHCTepCTBa o6pa303a1m51 PI HayKn Poccnficxofi (Denepaunn. PesyJILTaTLI
`
`PICCJIBflOBaHI/ISI
`,ILOJ'IOXCGHBI H oficyxcnenm Ha: VII
`11 VIII chepoccnficxofi c
`
`MCXClIyHapOJIHBIM yqacmeM HlKone-Kombepemmn no (bl/1311011011111 MBIHIII H
`
`2‘
`~ M-Lnneqnofi nexrenbnocm «HOBBIB 110117101131
`1c KByqumo Knaccnqecmx
`
`(Mocxna,
`2013,
`2015); Bcepoccnficxofi Haquo—npaxmqecxofi
`«I/IHHOBaImOHHLIe
`Texnonomn
`1103311113an
`
`2013); XXII (meme (bnsnonomqecxoro
`
`' V POCCHfiCKOfi
`
`Kombepeuumd
`
`«VIIpaBJIeHHe
`
`
`
`PBBYJIBTaTLI PICCJICJIOBaHI/Ifi H MeTOJII/IKa OLICHKI/I CHHOBBIX BO3MOX€HOCT6§I
`HBI
`I/I HpI/IMCHfiIOTCSI B CHOPTPIBHO~
`JpOBIrITCJ'IBI-IOM KOMIIJICKCC «CTpeJIeu» OOO <<Fa3np0M TpchraB CaHKT-
`
`choncxoe
`IIHYW,
`MyHIIIIlI/II13JILHOM
`
`aHmI 1.1616171 «ILCTCKO-
`
`
`prmypa n 063%! nuccep'raunn. HuccepTam/m, O6’BCMOM 115 crpamm
`
`‘TeKCTa, COCTOI/I'I‘ K3 BBCJIGHI’IH III
`5
`I‘J'IaB, BKJHOanOHIm 0630p
`
`CHI/ICaHI/IC MCTOILOB HCCIIEIIOBaHI/IH, HBHOKCHI/Ie
`
`IIByX aKTOB BHeflpeHI/Ifi.
`PCKOMCHllaIII/II/I, CIIHCKa JIPITepaTypBI PI
`
`)1ch 13 pncyHKOB PI 12 Ta6nm1. BHGJIHorpacpI/m 1310110112161: 196
`PICTO‘IHI/IKOB (107 OTC‘ICCTBBHHBIX, 89 KHOCTpaHHbIX).
`
`nx
`
`o6cymeHHe,
`
`
`
`Allergan, EX1083
`
`

`

`
`
`2
`
`1.1.
`
`061mm xapamepncmxa beme'moii cnnu
`
`CHJIOBLIe BO3MO)KHOCTH qenonexa HmeIoT cymeCTBeHHoe 3HaquHe B are
`
`HOBCCZIHCBHOfi
`
`PI prnoaofi RBXTCJIBHOCTH. Oco6o BameH ypOBeI—IB pawl/mm
`
`
`
`
`
`
`
`,_
`_, CHJIOBBIX BosMoxcHoc'refi mm nocmxceHHx BBICOKI/IX pBSYJIBTaTOB BO MHOI‘HX
`Bnnax cnopTa (IO.B. Bepxomancmfi, 1993; EH. HHaTOHQB, 2004; AA.
`
`
`BHemHee COIIpOTPIBJIeHI/Ie mm npomBozzefichonaTL eMy 3a cqe'r aKTKBHOCTPI
`_MLIIIII.I (B.M. BauflopCKI/Ifi, 2009). B (bnanonorm/I pawn/mam": a6conIoTHon PI
`THbCI/ITeJILHyIO MBIIHe‘iHyIO cuny (P.V. Komi, 1986; C10. Bepmnumfi, 2005).
`comomofi cnnofi HaBHBaIOT amomemde MaKCHMaIILHofi MLImequfi emu K
`
`. BacnneHKo, 2006). H011 cnnofi HOHHMaeTCX cnocoGHOCTb "IBJIOBeKa npeononeBaTL
`
`
`
`
`
`
`(H/CMZ mm KP/CMZ). OTHomeHne MaxcuMaJILHofi Mmmeqnofi 0mm K 66
`MI/I‘IeCKOMy nonepetlnmcy - TOJIHIHHC B HeJIOM, OHPBflBHflCMOfi
`HHbfi omenLHLIx MLImeqHHx BOJIOKOH, HaBBIBaeTCfl omecmenmofi cnnofi.
`
`
`
`
`
`mnax
`
`MBIIIIB‘IHLIX
`
`coxpamennfi:
`
`uaomerpnqecxom,
`
`
`3:1
`~_KOM, BKCIleHTpW-IBCKOM n HsoKHHeTmeCKOM (HE. AHHCHMOBa,
`ripa‘yax, 1985; TJI. HeMHpOchax, 2003; H.M. Tap6eeBa, 2013).
`e' 3T0 COKanleI-IPIC MBIIJIIIBI, HPH KOTOpOM OHa pasnuBaeT
`
`
`Allergan, EX1083
`
`

`

`Hanfionee 3Ha‘II/IT6JIbHaSI cuna B cpaBHeHHH c prrI/IMH THHaMH MLImequro
`coxpameHIrm. I/IsomneTI/mecxocxoe -— 3T0 coxpameHHe MBIIHHLIOGecneqHBaromee
`H3MeHeHHe
`cyCTaBHoro yrna c HOCTOXHHOf/i cxopocrmo an KOMfieHcaHHH
`
`HanpxxceHI/m
`
`MBIIIIH
`
`nocpeJICTBOM perynqu/m BHemHero
`
`MBHBIHB Hanpsnxem/m MHIHIILI. BKCHeHTquecxoe cdxpameHI/Ie nponcxozmT B TOM
`cnyqae, 601111 BHCHIHSUI Harpy31<a 6011mm: passnBaeMoro Mblmuefi ycnnm, a caMa
`Mmuua leII/IHSICTCSI. HpH TaKOM name MLImeHHoro coxpameHHH pa33HBaeTca
`
`
`
`
`
`
`
`
`meHsuomero
`
`
`L'_‘ COHpOTI/IBJIBHHX. Coxpamenne TaKOI‘O TI’Il'Ia IIOCTI/Il‘aeTCfl TOIIBKO an/I HOMOUIH
`CHCHKaJIBHBIX HHHaMOMeTpHHeCKHX yCTpoiz’ICTB.
`211151 oGecnequHx HocIoaHHofi
`
`'cKopoc'rH HepeMCIIIeHPI}! BHeUlHflX Harpysxa Bospacrae'r B Tex OyCTaBHBIX yrnax,
`
`flme Mmmua MOXCCT paBBI/IBaTB 3HaqHTeJILHoe HanpaxceHHe H, Hao60p0T, Harpysxa
`
`yMCHLLIIaeTCH npn Tex yrnax, B KOTOpBIX, MLqua pasBHBae'r MCI-1511186 ycmme
`
`WCKymexac 1988; RM FOPOJIHI/I‘IBB, 2005, CA. MOHCBBB, 2010).
`
`_- OnpeneneHHe MBIIHe‘iHOfi ovum y Henonexa ocymecTBnHeTcsi B npouecce
`
`pommnmoro yer/mm, CTpeMJICHI/Ifl MaKCKMaJIBHO COKpaTI/ITB PICCJICJIYCMBIB
`L H (101/1. FpanHa 2012). B 3T0M cnytiae paBBmaaeTca MaKCHMaHbHaSI
`" ”3Boana51 cnna (MI'IC). Hpn paCCMOTpeHHH CI/IJIOBBIX BOBMOXCHOCTef/i KaK
`
`
`
`QTHO HJIOBBIMI/I CHOCO6HOCT$IMH I'IOHPIMaeTCSI yMeHne Henonexa paBBKTL
`eycmme B KpaTqafimnfi HpOMexcyTOK BpeMeHH (ILB. HOIIOB H up,
`
`
`
`mieme Mbmm, mm 060Hx KOMHOHeHTOB. O6LIHH0 Hal/16011511114171 HpHpOCT
`
`HBHHIQTCH «asmeHax cuna» (B. POHHOHOB, 1966; AB. (DaneeB,
`
`
`
`Allergan, EX1083
`
`

`

`HpOHBJIeHKH _ szbnanofi 0mm Baxma He cromaxo Benz/mafia cymm, cxomsxo eé
`
`HapacraHHe B0 apemenn, T.6. r'pannem‘ chLI. PGSYJIBTaTI/IBHOCTL anonHeHm
`CKOpOCTHO-CI/IJIOBBIX ynpaxcHeHnfi TeM “BBIHIC, qu Menmfie mIHTenLHOCTL
`HapaCTaHI/IH cmm no eé MaKCHMaHBHOFO anaqemm. B Kaqecme cneumbnqecxoro
`
`
`
`
`
`(baKTopa HCKOTOpBIX CKOpOCTHO-CI/IJIOBBIX cnocoSHOCTeIVI Cl'IopTCMeHa lenemo'r
`
`peaKTI/IBHBIC caofiCTBa MBIUIII. OHI/I HpOfiBJIflIOTCSI B anxceHfixx, BKJIIO‘iaIOIlII/IX
`
`MFHOBeHHOC nepexmoqenne OT yCTynaromero K npeononenammemy pCXCI/IMy
`
`pa60TL1 anm, H xapazcrepnzymrcx TBM, ‘ITO Benntha npeozxonesaronmx ycnnnfi
`
`cyIIIeCTBeHHO BospacraeT non
`BIII/IHHPICM
`IIpeIlBapI/ITCJILHOI‘O
`
`(<l'IpI/IHyILHTeJILHOI‘O» paCTSII‘I/IBaHI/ISI pa60Tanumx MBIUIH' 3a crieT mnemqecxofi
`
`3Hepr1m nepeMemanmeficx maccm (EA. HIHpKOBeu, 2003).
`
`MaKcnmanLHax
`npomnonman
`cnna
`sasucm OT MLImetIme
`(nepmbepI/Iqecmx) n KooanHaumHme (IICHTpaJIBHO-HepBHBIX ¢aKTopOB) (ELM.
`
`K011, 1986). K MblmeqHLIM (HepmbepI/I‘ICCKI/IM)
`(lJaKTOpaM, onpenenmomHM
`
`nponaaonsno pasnuaaemyro MaKCHMaJIBHyIO cnny omocarcx cnenymmne: 1)
`
`mm MBIIIIII, nocKoany ycmme Mmumm sasncm OT 66 ILJIHHBI; 2) ycnomm
`
`
`
`
`L ymemMLImequfi KoomeHam/m. CIpyKTypHo-tbyHKunonaHLHax
`
`fipOHaJIBHBIX CeTefi FOJIOBHOI‘O I/I CIIPIHHOTO MOBI‘a OGBCHG‘II/IBaeT
`
`
`
`Allergan, EX1083
`
`

`

`IKE OHPBHCJIHIOT KOJ'IH‘IBCTBO I/I I13.0TOTy HepBHBIX PIMITYJILCOB, HOCTYI'IaIOIIlI/IX B
`1/1
`CKCJICTHBIB MBIIIIIIBI
`0T MOTOHefipOHOB CHHHHOI‘O MOSI‘a,
`
`OILI/IHO‘IHBIX coxpamennfi PIX BOJIOKOH K
`
`o6ecneqHBaI0T nepexon OT cna6mx
`TaHmeCKHM. C HOMOIHBIO naHme MeXaHI/IBMOB mome'r nocmraTch
`MOLIIHBIM Te
`MaxcmanLHoe 3Haqune nponssonbao meHBaeMofi MLImequfi 01mm. Bennqmia
`L1H I:ICJIOBCKa 32131101111“ 0T WCI/IJIBI coxpamenm
`
`
`
`
`
`
`
`MHC OTHBJIBHOfi CKeJIeTHofi MBIHI
`I/IMaJIBHafl cnna Konxpemofi MLIIJIIIBI passnnae'rcx mama npu
`
`npymx MBIHIH. Marco
`cosepmeHHofi MemMLImequir’I KooanHam/m, o6ecneananmei71 onTnMaJILHLIfi
`
`1351601) MBIIJIII -- CHHepFHCTOB, nonnxcenne aKTHBHOCTH MBIIJIII, -— aHTaI‘OHI/ICTOB H
`
`HOBBIHICHHC ycmmfi MHUJII, @nxcnpyloumx coorBeTCTBonmne cmexcnme cycraBLI
`
`[(IO.C. CaHIIHHCKaC, 1990; EH. Romance, 1994; EH. KprIcL, 2004; LLB.
`
`
`
`MeflBeILSB, 2007).
`Cnenyer nonqepKHyTL,
`
`two ynpaBneHHe MBILIILIaMPI, Korna Tpe6yeT051
`fiBJIiIBTCH CJIOXCHOfi 33113‘16171
`
`
`
`1115111111 Menbme B cpaBHeanI 0 xx
`ocmmynmmo caMnx MBIHILI. Paammy mequy
`a10T CPIIIOBLIM nechuHTOM
`
`yCHIIPISIMH, pQBBI/IBaeMBIMPI B OTBCT Ha
`
`
`:T'aH-qucxyro aneKTp
`014110171, BBIBBIBaeMOf/i anexpocmMynHuuei’i, HaBLIB
`
`M. 'Kou, 1986).
`
`1160 neHTpanLHoe ynpaBJIeHHe MBIIIIe‘II-IBIM annap
`qu coBepmeH
`
`0 01411030171 nednmm naHHofi MLImequfi rpymm. BequuHa cunmaoro
`
`SMOIIKOHaJIBHOFO
`ncnxonomqecxoro,
`112121
`3a13n0m 0T:
`
`a onHoneMeHHo aKTHBpreMLm MBIUquHBIX rpyrm;
`émoro; KOJII/I‘ICCTB
`
`Ty MBIIIIIIaMI/I (RM.
`CCBepHIeHCTBa ynpaBneHI/m BOBJIe‘ieHHBIMH B pa60
`
`6 M..H Stone eta1., 2007; DJ. KidgelletaL, 2010).
`
`pememm JIBHFaTeJIBHLIX sanaq, Tpefiyromnx HpOiIBJIeHI/Ifi paBIIHqHBIX
`
`
`' rynmmsl qaCTOTLI nMnyJILcauun MOTOHefipOHOB;
`
`1415111
`
`
`
`Allergan, EX1083
`
`

`

`prdmnxenb, IO.C. HCBPIK, 1985; RM. Enoka, 1988).
`1. Kommecrao aKTPIBHBIX nanra'renmmx BHKHI/III. HOCKOJILKy Kaxmaa
`T051 MHOI‘I’IMI/I MOTOHefipOHaMI/I, I’IMGIOUII’IMH paBHBIe HOpOFPI
`HefipOHOB (11E) HBHHCTCX
`
`MBIIIIIIa I/IHHCPBPIpye
`
`Konmecma aKTHBHBIX
`
`peryTI’IpOBaHI/ISI, HBMBHEHHB ‘II/ICJIa aKTI/IBHBIX MOTO
`BaXCHBIM CHOCO6OM pCI'YJIHLII/IH CHJIBI coxpamemm MBIHIII. C YBBJII/I‘ICHHCM
`11E BospacraeT n paaBnBaeMax )IaHHOfi Mblmuefi cana.
`eHo, VITO He6onbume
`
`
`
`
`
`
`
`
`B Ha‘anIe 30—x ronoa npomnoro Bexa 6mm yCTaHOBJI
`MOTOHCfipOHI-JI, HHHBpBPIpyTOIIII/Ie MBIUIBHHBIC MBIIIIIIBI, aKTI/IBI/IPYIOTCEI Heme, 116M
`
`LI, cocrammonme 6BICTpI>Ie 11E. Bonpoc o nopanxe
`60.1168 prIIHBIe MOTOHefipOH
`
`,ZIE Hau6onee 110mm szqaflcx 3. XeHHéMaHOM,
`
`peryTnpOBaHm
`opxmca
`aKTHBaunH ,IIE
`1'1
`CTepeOTI/IHHOCTB
`PI
`noxaaan
`HBHBMBHHOCTL
`
`COOTBeTCTBI/IYI
`c
`pa3Mep0M nx MOTOHefipOHOB (E. Henneman,
`
`HCHBHOCTH 13036y>1<na10mux BJIHHHI/Ifi Ha MOTOR
`
`'yBeJnmeHneM nHTe
`(pepnqecxnx peuenTopOB
`f‘c'roponm ueHTpanLme MOTOpI-ILIX CprKryp p1 nepn
`
`,npemxe Bcero aKmBnpymTcs MaHeHBKI/Ie, MEMBHHBIC HE. Hp»: naJILHefimeM
`,yCmIeHuu Boz6yx<11a10mnx maxim/1171
`B
`pa60Ty
`BOBJIeKaIOTCX
`
`yCTofiqHBLIe
`K
`yTomneHmo
`JIE.
`BBICTpBIe,
`6L10Tpo
`y’I‘OMJDIeMBIe
`
`aKmBnpymTca nocneanMK, npm nocrmKeHun cmm coxpamemm B 20 —'- 25
`
`upOHeHTOB OT Maxcnmanbnofi.
`
`CneJIOBaTeJILHo, nopmox amalgam/In 11E onpenenxercx‘ CO6CTBCHHLIM
`
`”- qu meHLme pa3mep MOTOHefipOHa,
`
`, Hume H0p01" ero aKTHBamm
`HaBBIBaETCSI npnmmnom pasMepa mm npnmmnom XeHHemaHa.
`caMLIe mansle ILE MBIUIIILI awn/11311131 11pm J11060M 66
`
`e, GLICTpLIe HE, onmeme E COCTaB naHHOfi
`
`naéfio 3T0My anHuuny,
`
`6mm, Toma KaK 60115111121
`my: npn 60115111le ycnmmx. HoaTOMy y 02m
`11E no CpaBHeI-IPIIO c
`
`_'_:7’aKTI/IBHBI JIPI
`
`TBIICHB KCIIOJIBBOBaHI/ISI Gonbmnx, 61,101?me
`
`enneHHHMpI eflKHI/IHaMIrI, MeHLme (RM. Snow, 1998).
`
`
`
`Allergan, EX1083
`
`

`

`32111211111 (11.11. Kym/ma, 1983; A.IL>K. MaK-KOMac, 2001; RM. CamTOB, 2001).
`E01111 11pm BBII'IOJIHCHI/IPI JIBPIXCCHPUI MBmma 1101mm pawl/1'11: HeGOanym cmry, TO
`K 66 MOTOHefipOHaM Hocrynaer 011216131171 HOTOK HepBI-IBIX HMIIyHLCOB. B 01351314 0
`"IBM, 1110 B COCTaB 111060171 1111111111131 onmn PI Gunpme, u MemeHHBIe 11E,
`omnqammueca pasMepaMn csonx MOTOHefipOHOB, peaKmm LIE 11a 3101: HOTOK
`HepBHBIX HMHyHBCOB pa311mxa. AKTPIBHOCTB BOBHYIKaeT 11111111: B MeJIJIBI-IHLIX 11E,
`KMeIOIlII/IX 11660115111146 pasMepLI MOTOHCfiPOHa, a, CJIelIOBaTeJILI-IO,
`
`
`
`
`
`
`
`
`
`
`noporn peryTHpOBaHmI. BBICTpLIe 1113 y 112111110171 MLIIJmLI B STOM cnyqae He
`’aKTI/IBprIOTCH. HoaTOMy 1114311313011 cna6mx ycmmfi MBImuBf ofiecneqHBaeTcx
`
`aKTHBHOCTLIO TonLKo MBILJIBHHBIX, ycrofianHx K yTOMJIeHmo 2113 (11111 S).
`
`11pm BLInonHeHHH nBHmeHm, Tpe6y10mero 601151110171 0111151 corcpamennx
`
`eé MoronefipOHBI
`IIOllBCpI‘aIOTCSI
`303116120131110
`Raflfiofi MBIIHHLI,
`
`1976). 3170 HpHBOlIKT K
`Ki—iTCHCI/IBHOI‘O HOTOKa HepBHBIX HMHyJILCQB (P.C. Hepcon,
`
`CHI/FICHI/IIO 1E11/101121 aKmBprIOmecx LLB. KpOMe MenneHHBIX, Hnsxonoporonmx
`
`I; I_BBKmOIIa10T051 B pa60Ty H 65101311316 Bmcoxonoporoame 11E.
`
`capaCTaeT HHTCHCHBHOCTB 13036y>1<11a1011111x BIIYUIHPII/I Ha MOTOHeYIpOHBI, TBM
`
`ee prnHBIe r10 pazmepy JIE BOBJIeKaEOTCSI B pa601y.Cnen013aTenLHo,
`
`L
`“113115112151 0111121 coxpameHwI 113111111121 o6ecneanae'rcs aKTHBHOCTBIO 11E Bcex
`
`eX-‘TIIHOB (S, FR, FF).
`
`11pm cna60M coxpamemm
`'qaCTOTa HMnynBcamm MOTOHefiponon.
`
`'1'me MHIIIII qacrora HMnyJILcauHH coccraBmIeT 5— 10 F11. B TaKOM
`21301-16txaCTOT 11a>Ke MeJIJIeHHLIe ILE 6OHI>HIPIHCTBa MBIHIII paGOTaIOT B pexche
`
`
`
`‘ 1011116012510)- aKTI/IBHOCTI/I pa3H1>1x 11E.
`
`
`
`
`111.1 qacrora 1321313512103
`51/1.fimaHHHac, 1983). 11pm cane coxpamean, paBHofi 30 % — 60 %
`Q12; iqacmra HMnynBcaImH )IE 11001111391 20 ~— 30 F11, a 11pm
`
`Allergan, EX1083
`
`

`

`
`
`
`,ILOKaSBIBaIOT y‘IaCTI/Ie ‘MexaHI/I3Ma HBMGHBHHSI
`F11. HSJIOXCCHHBIB BBIIIIC (baKTBI
`
`qaCTOTLI HMnyJILcauHH 11E B perymum/I emu coxpamenm MBILIIII. qu BBIHIC (no
`
`TeM GOHLIUe
`onpeneneHHoro upenena) ‘IaCTOTa I/IMIIlebcaHI/IPI OTJIeJILHofi DE,
`
`
`65 small B passnBaeMoe
`cnna coxpameHna 6'6. MBIIIIC‘IHBIX BOJIOKOH I/I TBM 6031121116 e
`
`13er MLImuefi ycmme. mm Kaquofi omenLHou 11E xapaKTepHo onpeneneHHaa
`
`I/I KOTOpOI/I CI/IJIOBBIB B03MODKHOCTI/I BCBX ee MBIIIIC‘JHBIX
`
`- BOJIOKOH peam/Iayro'rcz I'IOJ‘IHOCTBIO. Perymmm 01mm coxpamennx anmm ny'reM
`
`-I/I3MeHeHI/IS{ ‘IaCTOTBI nMnynbcaImn 11E HaH6onee BLIpaxceHa'y 6mcrpmx 21E.
`
`qaCTOTa 3036y>1<nemm omensnofi LEE onpeneme'rcx I/IHTCHCHBHOCTLIO
`
`,'__anxo,u51mer0 nomlca HepBHBIX PIMl‘IyIIBCOB, Bosneficmyromero Ha MOTOHei/‘Ipon
`
`
`giaHHoi/i
`IKE. ECJIH HHTBHCHBHOCTL 3036mm
`
`He memleHHbIe IEE, KOTOpBIe nmnynbcnpylo'r c
`BKJIIO‘IaIOTCfl JIKIIIB HHBKOHOPOI‘OB
`
`CBBICOKOI/I
`‘IaCTOTOI/I,
`
`THOCPITCJIBHO H
`nHHquoro coxpamerm PI 3Y6‘IaTOI‘O TeTaHyca. T
`
`
`cnnofi
`_’ycneanaeT
`coxpameHHe Mmumm c
`ymepeHHofi
`
`QnOnmnTenLHoro BpeMCHI/I.
`I/IMeHHo
`B STOM nuana30He pa60TamT HE
`
`
`
`lIOCTaTO‘IHOI/I LUIS! 0660116qu
`aKaSI qacrora uMnynLcaunH HE
`
`qaC’I‘OTa PIMIIyIIBCOB, IIp
`
`mnx BJII/ISIHI/Ifi HeBeJmKa, TO
`
`3151 T6113.
`
`COKanleHI/Ifi MLIHIIIBI
`
`nocmrae'rcx
`
`
`
`
`aKofi cnnofi He
`
`Allergan, EX1083
`
`

`

`YBGJ‘II/I‘IBHI/ISI qaCTOTm I/IMIIyJ'IbcaIlI/II/I ILE c yBennquneM ycum/m MBIIIIHBI Tpe6yeT
`
`qaCTOTe HMnyJILcaunu (mamcoro TeTaHyca), noxaaano, qTo nocnemmx B
`HGCKOJIBKO pas 60111511113. CJIelIOBaTeJILHO, peryTnpOBaHpie Bcéx ILE an Hnsxofi
`HaCTOTe HMHyJILcauKH o6ecnermBaeT MeHLmHfi npnpocr CHJILI, tIeM TOT, KOTopLIfi
`
`3HaHm71 o MachIManLHHx BOBMOXCHOCTHX KEDICJIOI‘O n3 HHX. Conocramerme 01mm
`coxpameHmI MBIIIILI
`IIpH caMofi Hnsxbfi
`qaCTOTe
`PIMHyfibcaIIPII/I HX IIE
`(ycpenHeHHofi 0mm 3y6anoro TeTaHyca) c canofi, passnBaeMofi npn Bmcoxofi
`
`
`
`
`
`
`
`
`r1T0 B paBBI’ITI/Ie CHJILI coxpamemm
`nae]: YBGJIPI‘IBHI/IC I{EICTOTBL 3T0 03HaHaeT,
`
`" MaKCHMaJIBHLIB BOBMOKHOCTI/I "IaCTOTHOI‘O MCXaHH3Ma 6031121116 MaICCHMaJIBHLIX
`
`
`BosMomHOCTef/i MexaHmMa peryTPIpOBaHI/ISI. B paanqHLIx nuana30Hax CI/IJ'IBI H B
`
`paSHBIX yCJIOBKSIX coxpam’eflm BOSMOXCHO KaK napannenLHoe HCHOJIBBOBaHPIC
`OGOI/IX MexaHI/ISMOB LUIX yBeHPI‘ICHI/IH CPUIBI MLIIIIC‘IHOI‘O coxpamennx, TaK PI
`
`H BHMYIIICCTBBHHOB HCIIOIILSOBaHKe OJIHOI‘O K3 HKX. B peaJIBHBIX YCJIOBI/IHX
`
`
`
`n‘anawHe OT 0 % no 50 % MaKcnmanLHofi cunm cOKpameHmI, nocne qero
`BHeKaeTcx
`III/11111:
`HC6OJIBIHOC
`(oxono
`10 %) Konnqecmo Hanfionee
`
`
`coxonoporwmx EB,
`21 yBenuqune (:14an OT 75 % no 100 % nocmrae'rcsx
`cmquTenLHo 33. war pOCTa qaCTOTbI KMIIyJILcanHH (AA. FHAHKOB, 1975, P.C.
`
`CQH, 1985; BC. prqJKHKenL, ICC. 116an, 1985; ILA. HBTPOB, 2001).
`
`3 CHpronnsaum coxpamenm MblmeqHLIx BOJIOKOH omenbnmx 1113 B0
`
`Mefin. . CoxpameHHe MBIIIIIIBI Bcema ocymechJme'rcx npn aKTHBHOCTH
`'11 max mm MHorpIx 11E. XapaKTep BpeMeHHofi B3aHMOCB5I3PI aKTnBHocm'
`
`
`
`
`
`[O‘VIHOI‘O coxpamennx, T0 COKpaIHeHHe MBIIIIC‘IHBIX BOJ'IOKOH KWOI’I
`T; c COKpaIIICHHeM prrl/IX 11E. CJIBIIOBaTeJILHO, coxpamenpm Tpex
`
`Allergan, EX1083
`
`

`

`omenmmx IE 14 MLIIIIIIa pasmmaeT CpaBHFITeJIBI-IO Gonsmyro cmy. Hao6op0T,
`
`ecnn Tpn 11E COKpaIIlaIOTCfi aCHHXpOHHO (He omioapemeHHo), TO cymmaunn He
`nponcxozmT PI MBIIIIIIa
`pa3BHBaeT MeHbmym cnny. B yIIBpBOM cnyqae
`HaGJIIOJIaIOTCSI 3Haqmenbnme KoneGame 01mm Mblmequro coxpamenm, BO
`
`
`
`
`
`BTOPOM 01m cymeCTBeHHo MeHLIIIC. 3T0T anMep CBI/IJIB’I‘BJIBCTByeT o TOM, qTo
`
`npn pa6o're IIE B pemme onuHquoro coxpamenm abnnxpOHHocrb FIX
`
`~aKTI/IBHOCTI/I
`oGecneqHBaeT
`cmaxceuHOCTL
`COKpameHHfi
`Bcefi MLIIHHBI.‘
`
`
`,ijeJII/I'LICHFIE rmcna aCHHXpOHHO pa60Tammnx HE npuBozm'r K yMeHBIIIeHI/IIO
`,Kone6aHI/Iiz'1 B Hanpxxcennn MBIIIIIIBI,
`1L11:0
`cnoco6cn§ye1r 6onee
`
`a-BBIIIOJIHeHI/IIO PI TquOMy nomepxcanmo T0171 mm 14110171 1103131: B eCTeCTBeHme
`
`yéhOBHxx mnanenexTenLI—Iocm GoanKHCTBo [1E MLIHIIIBI pa60Ta10'r aanxpOHHo.
`
`3 (:qu 3mm nocmfaemx ornameHHOCTb coxpameHm MBIUJIJ; B ycnommx, Roma
`
`’LImeqHHe Bonoxna 11E 143-3a Hnsxofi qaCTOTLI nmnynbcaunn MOTOHefipOHOB
`_zpa66;ranT B pexcume ommoqnoro coxpamemm mm 3y6qaroro TeTaHyca.
`
`HopManLHax
`BpeMeHHafi
`0135131,
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`
`Allergan, EX1083
`
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`
`
`Allergan, EX1083
`
`

`

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`Allergan, EX1083
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`
`Allergan, EX1083
`
`

`

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`
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`
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