LV10685B - Device for transdermal administration of dexamedethomidine - Google Patents

Device for transdermal administration of dexamedethomidine Download PDF

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Publication number
LV10685B
LV10685B LVP-93-1079A LV931079A LV10685B LV 10685 B LV10685 B LV 10685B LV 931079 A LV931079 A LV 931079A LV 10685 B LV10685 B LV 10685B
Authority
LV
Latvia
Prior art keywords
layer
dexmedetomidine
contact
skin
adhesive
Prior art date
Application number
LVP-93-1079A
Other languages
English (en)
Other versions
LV10685A (lv
Inventor
Kenneth J Colley
Donald R Wilson
Gary W Cleary
Lammintausta Risto
Jalonen Harry
Original Assignee
Cygnus Therapeutic Systems
Orion Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cygnus Therapeutic Systems, Orion Corp filed Critical Cygnus Therapeutic Systems
Publication of LV10685A publication Critical patent/LV10685A/lv
Publication of LV10685B publication Critical patent/LV10685B/lv

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

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  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

LV 10635
yCTPOftCTBO flJlfl TPAHCflEPMAJlbHOrO BBEflEHMfl flEKCMEflETOMMflUHA
OnncaHue Q6nacTb τθχημκμ 3T0 Μ3θ6ρβΤΘΗΜΘ OTHOCMTCB B OCHOBHOM K Η33Η3ΜΘΗΜΚ) fleKCMeTOMMflUHa flna ycnoKomenbHbix, γμποτ6Η3μβημχ, 6ojieyTonaiomMx Μ/ΜΠΜ TpaHKBMJIM 3MpyKDL4MX μβΠβΜ Μ, 6θnee ΚΟΗΚρβΤΗΟ, OTHOCMTCfl K cnoco6y m ycTpoiicTBy jļna ββθαθημβ neKapcTBa 4epe3 KO)Ky. Πρθπποοηπκμ κ co3aaHmo μ3ο6ρθτθημβ
MefleTOMMflMH UTĪM 4(5)-3ΡΒφ3-ΜΘΤΜΓΙ-213-ΑΜΜΘΤΜΡ6βΗ3ΜΡΜΜΜΑ330Γ1, MMeioaļMM CTpyKTypHyio 4>opMyjiy ir flBJIfleTCfl CpaBHMTePbHO HOBbIM J16KapCTB6HHblM Cpe^CTBOM, ΚΟΤΟρΟΘ
M3BecTHo xax noTeHiļMaPbHoe m ceneimīBHoe Bemecreo, o6jiaAaiomee cpoflCTBOM κ peLļenTopy anb<Ļa-2. Oho 6bino ΜΑβΗΤΜφΜμΜροΒβΗΟ b KaMecTBe 3ητμγμποτθη3μβηογο areHTa (ĒBponeiicKafl naTeHTHa« ny6nnKaLļMfl Ns 72615), BeTepnHapHoro ycnoKanBatoinero cpeflCTBa (EeponeiicKaH naTeHTHaa ny6jiMKaLļwi Na 187471) n TpaHKBHJiH3aTopa (ΠβτβΗΤ CLUA Na 4783477). MefleTOMMAMH, κθκ 3TO mojkho 33ΚΡΙομμτβ M3 ero CTpoeHMB (I), coflep)KMT cMecb οπτμηθοκμχ μ3ομθροβ; πρΜΓοτοΒ/ιβΗΜΘ, paaAejieHne μ oMMCTKa npaBOBpaiiļaioiiļiix m neBoepamaiomito M30MepoB onncaHa (cm. EBponeftcKyio naTeHTHyio ny6jiMKaLļnio Na 300652). Bbmo ycTaHOBneHO, mto npaBOBpaLAaK)LLļMM Μ30ΜΘΡ - "fleKCMeTOMUflHH" - PBfiaeTCfl aKTUBHblM 1 Μ30Μβρ0Μ, Β ΤΟ ΒρθΜΗ, ΚΘΚ Ι-Μ30ΜΘΡ ΠΒηΠΘΤΟΗ 3Η3ΜΜΤΘΠΒΗΟ ΜΘΗΘΘ fleiicTByioinMM. Β flononHeHne κ BbiiiiecKa3aHHOMy, πρΜΒΟΑητοπ cne,qyioaļMe ccbinKM, OTHOCflLUHeCfl Κ ΧΜΜΜΜ H φθρΜΘΚΟΠΟΓΜΜ ΜΘΤΟΜΜΑΗΗβ, ΘΓΟ ΟΟΠΘΜ H ΘΓΟ M30MepHbix κομποηθητοβ: A.Karjalainen, Acta Chim. Scand. (1988) 42:537-545; E.MacDonald m AP- Eur.J.Pharmacol. (1988) 158:119-127; E.MacDonald m AP-, Ann.Clin.Res. (1988) 20:298-310; R.Virtanen m AP·. Eur. J.Pharmacol. (1988) 150:9-14; R.G.Vickery m AP·. Anesth.Analg. (1988) 67:611-615; D.Stonberg m AP·, J.Vet.Pharmacol.Ther. (1987) 10:319-323; m M.Scheinin m AP·. Br.J.Clin.Pharmacol. (1987) 24: 433-451. flaHHOe Μ3θ6ρβΤΘΗΚΘ OTHOCMTCfl B HaCTHOCTM Κ ΒΒΘΑβΗΜΙΟ AeKCMeTOMUAMHa nepe3 KO>xy. Bbinn pa3pa6oTaHbi m ncnonb30Banncb MHoroMMcneHHbie ycTpoiicTBa a^a TpaHCAepManbHoro ββθαθημπ nexapcTBeHHbix npenapaToe; BBeAeHne neKapcTBa nepee κο>κγ xapaKTepn3yeTc« μηογμμμ npeMMymecTBaMM. Πρβ>κΑβ ecero, T3kom cnoco6 ββθαθημα BBrmeTcn cnoKOMHbiM, yAo6HbiM h aipaBMaTMMHbiM nyTeM ββθαθημπ neKapcTB. Β otom cnynae ycipai-meTcan3MeHflK3iAnecfl ckopoctm a6cop6L^MM m o6MeHa BeiiļecTB, xapaKTepHbie nnn opanbHoro npneMa, a TaiOKe McitnioHaioTCfl m APyrne HeoTbeMneMbie HeyAo6cTBa, HanpMMep, pa3Apa)KeHMe >KeAyAOHHo-KmiieMHoro Tpaicra m TOMy ποαο6ηοθ. TpaHCAepManbHaa noAana neKapcTBa C03AaeT βο3μο>κηοοτβ τθιοκθ β BbICOKOM ΟΤΘΠΘΗΜ ΚΟΗΤροηΠ KOHLļeHTpaiļMii B φΟΒΜ ΠΙθ6θΓΟ ΟΤΑΘΠΒΗΟΓΟ ΑΘΚβρΟΤΒΘΗΗΟΓΟ CpeACTBa. XapaKTepHblMM Π3ΤΘΗΤ3ΜΜ, KOTOpbie OriMCblBaiOT ycTpoiicTBa a*TpaHCAepManbHofi ποαθημ neKapcTB, flenatoTcn Πθτθητη CLUA NsNa 3,598,122; 3,598,123; 3,731,583; 3,797,494; 3,854,480; 3,923,939; 3,926,188; 3,964,482; m 4,717,568.
OAHaKO, HM B OAHOfi H3 Π pO LļMTM P0B3H HblX BbILUe CCbJTIOK Mm ΚΘΚΜΧ-nn6o Apyrnx, Μ3βθοτηβιχ 3anBMTennM, ηθ onncbiBaeTcn ycTpoMCTeo ftna TpaHCAepMaJībHoii noAaHM npu npneMe AeKCMeTOMMAMHa. Hm b oahom M3 M3BecTHbix pa6oT ηθ npuBOAflicfi AaHHbie no npoHMLļaeMocTM ko>km μπμ HopMaM TepaneBTMHecKoro npneMa β οτηοιιιθημμ α6κομθτομμαμη3. HaCKOJlbKO Μ3ΒΘ0ΤΗ0 33ΠΒΜΤθηΠΜ, Β T3K0M Cnysae, TpaHCAepMaJIbHblH πρΜΘΜ AeKCMeTOMUAHHa ηβπηθτοη noiiHOCTbio He3anBneHHbiMM ηθμ3Βθοτηβιμ β AaHHofi o6nacTH.
PaCKDblTHB Μ3θ6ΡΘΤΘΗΜΑ Γ/iaBHoft μθπβκ» μ3ο6ρθτθημπ nenneTca C03AaHne cnoco6a h ydpoMCTBa απ* TpaHCAepManbHoro npueMa αθκομθτομμαμηθ. flpyroii Lļenbīo H3o6peieHHH nenneTcn οο3Α3ημθ cnocoāa pņn ycnoKoeHna naiļMeHTa, κοτορωίί BK/nonaji 6w πρΜΘΜ naiļMeHTOM AeKCMeTOMUAMHa c ynacTMeM npeABapMTe/ibHO ycTaHOBneHHOM nnouļaAM ΗΘΠΟΒρβΧςηβΗΗΟΜ ΚΟ)ΚΜ Β ΤΘΗΘΗΜΘ ΟΠρθΑβΠΘΗΗΟΓΟ ΠθρΜΟΑΘ ΒρβΜΘΗΜ M C MCnOJ1b30BaHMeM HOpMbl ΠρΜΘΜΘ, AOCTaTOMHOM Α™ AOCTM)KeHMfl ycnoKOMTenbHoro θφφβκτθ.
Euļe oahom LļenbHD μ3ο6ρθτθημπ πβππθτοπ coaAaHMe cnoco6a TpaHCAepManbHoro npneMa α®κομθτομμαμη3 β οοηθτθημμ c γθηομ-ycnnnTeneM, npoHMLļaeMbiM απη ko>km. flpyrofi Aenbīo μ3ο6ρθτθημπ nenneTCB τθιοκθ co3AaHMe, TpaHCAepManbHoPi cMCTeMbi ņņn npneMa α3κομθτομμαμη3, KOTopan 2 LV 10685 ΒΚΠΚ)Η3βΤ MHOrOCnOMHbIM Κ0ΜΠ03ΜΤ M3 Ηβθγΐ11ΘΓΟ CJIOP, ΒΘρΧΗΘΓΟ, Heo6fl3aTexibHo cKperuifliouļero aflreaMBHoro cnon, ημ>κηθγο, κοητθκτηογο aflre3MBHoro cnon, κοτορωίί nepBOHananbHO coflep>KMT πθκθροτβθηηοθ cpeflCTBO, m bucoko nopMCToro cTpyKTypHoro npoMex<yTOHHoro cnon Mex<Ay flByM9 aflreaMBHbiMn cjioamm. ΚρΟΜΘ ΤΟΓΟ, B fla/lbHeMLUeM OnHCaHMM Μ3θ6ρβΤΘΗΜΡ> 6yflyT H3J10>KeHbl m flpyrne ο6ι>βκτω Μ3ο6ρθτθημα, κοτορωβ nnn cneiļnanMCTa 6yflyT OMeBMflHbi MacTMHHo m nocneAyK>u4MX ncnbīTaHuii linu CTaHyT ποηπτην m npaKTMMecKoro Mcnonb30BaHnn Μ3θ6ρβτβΗΜΗ. C oflHoii dopoHbi, M3o6pTeHMe npeACTaBnneT co6oii cnoco6 B03flBMCTBMfl Ha ΠβμΜΘΗΤβ CBflaTMBHblM CpeflCTBOM-nOCpeflCTBOM TpaHCflepMa^bHoro npneMa fleKCMeTOMMflMHa, to ecTb npneMOM γιβαηθητομ neKapcTBa nepe3 npeABapmejibHo ycTaHOB/ieHHyio nnoiiļaflb HenoBpe)KfleHHoii κοχοι, cnoco6, npeflnocbJ/ικοίί κ KOTopoMy nocny>KMno OTKpbITMe, MTO fleKCMeTOMMflMH, fleMCTBMTeilbHO, ΜΟ>ΚβΤ BBOAHTbCH Mepe3 KO>Ky c iļenbK) ΑοσποκβΗΜη >KenaeMbix o6iamx B03AeficTBMfl Ha opraHH3M. B ΠρΘ/1ΠΟ)ΚΘΗΗΟΜ Β0Πη0111βΗΜΜ napa/ie/lbHO C JieKapCTBeHHbIM CpeflCTBOM npMHMMaeTCfl TaioKe reH-ycnnnTenb κομηογο προημκηοβθημβ c τθμ, mo6bi AocTMHb ycKopeHHoCi nepe^aHU neKapcTBa. Tax Ka« CKOpocTb Bbieo^a AeKCMeTOMMflHHa m opraHM3Ma flocTaTOMHO BbicoKa, npeflnaraeTCfl, πτο6ω ΠρΜΘΜ ero pņvmca CTOJIbKO, CKOJIbKO 3TO ΗΘΟδΧΟΑΜΜΟ flJlfl ceflaTMBHoro B03fleiiCTBHfl.
CneflyeT οτμθτμτβ, hto xoth npeflCTaBneHHoe M3o6peieHne m HanpaB/ieHO Ha αθηοτβμθ αθκομθτομμαμη3 xax ceflaTHBHoro cpeflCTBa, HCn0^b30BaHHe B Μ3θ6ρβΤβΗΜΜ "Β03ΑβΜΟΤΒΜβ ΟΘΑΘΤΜΒΗΟΓΟ CpeflCTBa", 3aKHKmaeT b ce6e Bce ero noTeHi4nanbHbie Mcnonb30BaHna, BbrreKaiomne m ero aKTMBHOCTM b κθηθοτβθ BeujecTBa, o6naAatoiiļero cpoactbom k pei4enTopy anhdpa-2, HanpMMep, ero ncnonb30BaHne b KanecTBe ΓΜΠΟΤΘΗ3ΜΒΗΟΓΟ areHTa, TpaHKBnnn3Mpyiomero cpeACTBa, 6oneyTonnK)mero Μ.Τ.Π. flpyroM acneKT M3o6peTeHHB π peflycMaTpneaeT co3AaHne neneāHoii CHCTeMbl ΑΠΒ TpaHCAepMa/lbHOrO BBefleHMfl AaKCMeTOMHAHHa β φορΜβ κο>κηηχ HatcnaAOK (δηηιιιβκ). Ko>KHaa HaicnaAKa npeACTaenneT co6ofi MHOrOCflOMHblH Κ0ΜΠ03ΜΤ, COAepJKaUļMM ΒθρΧΗΜΜ M3HaHOHHb»fi CJIOM M ABa OTAeribHbix aAre3HBHbix cnon, hhjkhhm "κοητθκτηημ" aAre3MBHbiff cnofi cpaay roTOBMTCB TaK, hto coflep>KHT neKapcTBeHHbin npenapaT. llpeAnonaraeTCH TaiOKe, HTO MHOrOCnOMHblM Κ0ΜΠ03ΜΤ COflep>KMT BblCOKOnopUCTblH npoMe>KyTOHHbiM cjioh Me>KAy ABynn aflre3HBHbiMM cjioamh, HanpHMep, H3 ηθτκ3ηηογο MaTepMana hjim ποαο6ηογο eMy. 3τοτ npoMe>xyTOHHbiii cjiom 6/iaroAapfl ηθ/ιμημκ) nop rionHocTbio nponmbiBaeTCfl neKapcTBeHHbiM ΒθίμθοτΒΟΜ m nio6biM pacTBopHTeneM nrin conbBaTnpy»oinnM areHTOM, coAepMauļMMCfl BHyrpn ycTpoHCTBa, m csvņmr npex<Ae ecero b KanecTBe CTpyKTypnpyioiAero ycmiMBatoiAero cnoa, onpeAenntoiAero CKopocTb BbiAeneHHS neKapcTBa. ĶpaTKoe onncaHne dhcvhkob
PncyHOK 1 0Tpax<aeT nonepeHHoe ceneHMe ycTpoficTBa H3o6peTeHnn cpa3y nocne naMUHnpoBaHHn κομποηθητηβιχ cnoee. 3
PncyHOK 2 M3o6pa>KaeT nonepeMHoe ceneHHe ycTponcTBa, noKa3aHHoro Ha pncyHKe 1, nocne τογο, kbk cnon noflBepranMCb b τθμθημθ ΟΠρΘΑβηβΗΗΟΓΟ ΒρΘΜΘΗΜ B3aMMHOMy ΠρΟΗΜΚΗΟΒβΗΗΙΟ.
PncyHOK 3 Mnn(ocTpnpyeT ΓρθφΗΗβοκηβ pe3yjibTaTbi sKcnepnMeHTa, OnktCaHHOrO B ΠρΗΜβρβ 2.
Cnoco6 ocvmecTBneHUfl μ3ο6ρθτθημβ
TaKMM 06pa30M, Μ3θ6ρβΤβΗΜβ BBflfleTCfl HenOCpeflCTBeHHbIM pe3ynbTaTOM οτκρντμα 3aflBMTenen, ητο αθκομθτομμαμη mojkho BBOflmb ΗΘΡΘ3 KO>Ky flJlil flOCTM>KeHM« ΗΘΟδΧΟΑΜΜΟΓΟ oāuļero ΘφφθΚΤΘ 3ΤΟΓΟ JieKapcTBeHHoro npenapaia 6e3 KaKMX-nn6o πο6ομηνχ βο3αθμοτβμμ η οοποϊκηθημμ, KOTopbie HacTo ΒΒΠΒίοτοΒ pe3ynbTaTOM opanbHoro MJ1M flpyrnx BapnaHTOB CMCTeMamnecKoro npneMa. Cnoco6 Μ3θ6ρβτβΗηη BKntonaeT TpaHCflepMaJībHbiki npneM αθκομθτομμαμηθ c Lļenbto "ycnoKoeHnn" naLļneHTa, to ecTb ncnonb30BaHMSi ero b KanecTBe AePicTByK)aļero ceflaTUBHoro epeACTBa, ηπη απα πρΜΜβΗβΗΜΑ b κθηθοτβθ 3ΗΤΜΓΜΠΟΤβΗ3ΜΒΗΟΓΟ, 6oneyTOJ1BK)UļerO, TpaHKBHnM3MpyKDLlļerO epeACTBa M τ.π. Kax OTMeManocb Bbiiue, ece stu BapnaHTbi Mcnonb30BaHM« ββιτθκθιοτ H3 ΤΟΓΟ, HTO ΑβΚΟΜΘΤΟΜΜΑΜΗ OKa3blBaeT A^MCTBUe Ha θ^φθ-aApeHepreTHMecKoe cTHMynnpoBaHne.
Cnocoč ΒΚΠΚ)Μ3ΘΤ ΠρΜΜβΗβΗΜβ ΑβΚΟΜβΤΟΜΜΑΜΗΘ Μβρβ3 npeABapMTenbHO ycTaHOBneHHyio nnomaAb Henoepe>KAeHHOH ko>kh b τβηθημθ onpeAeneHHoro ΒρβΜβΗΜ ripu Hopiue npneMa, οφφβκτηΒΗοη pjm ceAaTMBHoro AeMCTBnn. Tax κβκ CKopocTb ohmctkm opraHM3Ma ot AeKCMeTOMMAMHa ββαβθτοβ αοοτθτοηηο BbicoKoii, πρβΑ/iaraeTCfl, πτοδω npneM neKapcTB npoAon>Kancfl b ύθηθημμ nepnoAa ΒρβΜβΗΜ, ηθο6χοαμμογο Arm ceAamBHoro AencTBnn. /ļnn AocTn>KeHHfl 3φφβκτηβΗ0Γ0 ypoBHB /īeKapcTBa β κροβη πρη πθγκομ οθαθτμβηομ B03AencTBnn, npeAnaraeMafl HopMa npneMa cociaBrmeT BennMHHy Me>KAy 0,10 m 200 MKr/nac, 6onee npeAnoHTMTenbHbiM αβπβθτολ nHTepean ot 15 ao 75 μκγ/ηθο, nepe3 ynacTOK ko)kh nnouļaAbK) ot 2,0 ao 90 cm2, 6onee npeAnoMTMTenbHO ot 10 ao 30 cm2. KonimecTBO neKapcTBa, nocTynaiomero Mepe3 KO>xy, mo>kho perynnpoeaTb PBAOM φθΚΤΟρΟΒ, BKJllOHaB ρθ3Μβρ Η3ΚΠ3ΑΚΗ, KOJIMHeCTBO nepBOHaMa/lbHO Βπο>κβΗΗθΓθ JieKapcTBeHHoro epeACTBa, ncnonb30BaHne reHa-ycnnnTenn προΗΜΚΗΟΒβΗΜίΐ ko>kh, ncnonb30BaHne pa3nnHHbix MaTepnanoB b npncnoco6neHnn atih noAann neKapcTBa n τ.π. 6 ΗβκοτορΗχ cnyHaax MenaTenbHbiM ηθηηβτοη ObicTpoe co3AaHne BbicoKon KOHLļeHTpaLļnn A®KCMeTOMHAHHa b nna3Me. 3το μο>κθτ 6biTb ocyuļecTBneHO πρηΜβΗβΗηβΜ BToporo, 6bicrpo ncTomaeMoro TpaHCAepMa/ibHoro ycTpoiicTBa - b Αοπο/iHeHne κ ycTponcTBy HyneBoro nopflAKa, cooTBeTCTBy to mēro n3o6peTeHHto. 3to AononHMTenbHoe ycTponcTBO noAaeT čonbtuoe nepBOHananbHoe KonnnecTBO AeKCMeTOMMAMHa απη ycTaHOBJieHMft y cy6teicTa βφφβκτηΒΗοη κοΗμβΗτρβμΜΜ, nocne nero KonnnecTBo ero naAaeT 3KcnoHeHnnanbHo ao Hynn β TeneHne nepnoAa BpeMeHM 0,5-2 naca. TaKMM o6pa30M, oāiiļee B03AencTBMe BicmoHaeT nepBOHaHanbHyto Bbicot<yto KOHiļeHTpaiļMto, KOTopan nocTeneHHO CHM>KaeTCB ao npneMa ycTofiMMBoro ypoBHH, co3AaeaeMoro noAatouļMM ycTpoiicTBOM Hyneeoro nop«AKa β οοοτβθτοτβμμ c Μ3θδρβτβΗΜβΜ. flononHMTenbHoe ycTpoiicTBO πρηΜβΗΗβτοη 4 LV 10635 npeflnoMTMTenbHO κ yMacTKy ko>km c βηοοκοΗ npoHMiļaeMocTbio, TaKOMy KaK no6. TaKap cncTeMa ocoāeHHo none3Ha απρ ncnonb30BaHMP b xnpyprnMecKofi aHecTe3nn, npn κοτοροΑ flononHmejibHoe ycTpoūcTBO b coneTaHMu c ycTpoficTBOM Hyneeoro noppflKa AaeT αοοτθτομηοθ κο/ιμμθοτβο AeKCMeTOMUflUHa απρ aHecTe3nn πβψιβΗτβ, nocne μθγο cneflyeT nepnofl 6oxiee ημ3κογο nocTonepaLļnoHHoro ceASTUBHoro bo3A6mctbmp, cosAaBaeMoro oahmm ycTpoficTBOM HyiieBoro nopPAKa. npeAnoHTmePbHofi χμμμμθοκοΑ φορΜοίί απρ TpaHCAepManbHoro ββθαθηιιρ AeKCMeTOMMAHHa ρβρρθτορ οβο6οαηοθ ocHOBaHue, TaK xax κοχο PB/ipeTcp 6onee npoHmļaeMoii απ* οοηοβηοΑ φορΜΒΐ neKapcTBeHHoro BeuļecTBa, μθμ pj\a ero conefi. Oah3ko, ripu μθγοηιλμ, MoryT πριίημMaTbcp TpaHCAepManbHO KucnoTHbie aAAMTMBHbie cojim neKapcTBa c yneTOM τογο, MToncnonb3yK)TCP coJiHD6nnn3MpyKDLAne areHTbi, a τβιοκβ, πρθαποητμτθπβηο, ycnnmēnu npoHMLļaeMocTM ko>km. Tāme Kuc/ioTHbie aAAMTMBHbie cojim MoryT 6biTb npuroTOBPeHbi, HanpuMep, c HeopraHMMecKMMM κμοποτ3μμ, T3KMMH, KaK XJ10pMCTOBOAOpOAHaP KMCPOTa, 6pOMMCTOBOAOpOAHaP KMCTlOTa, cepHap KMcnoTa, a30THap KMcnoTa, φοοφορΗβΡ KMcnoTa μ τ.π., m c opraHUMecKMMM KucnoTaMM, TaKMMM, KaK yKcycHap KMcnoTa, nponMOHoeap KMcnoTa, rriMKoneBap KMcnoTa, nnpoBMHorpaAHap KMcnoTa, uļaBeneBap KMcnoTa, PČPOHHap KMcnoTa, ManoHoeap KMcnoTa, PHTapHap KMcnoTa, ManenHOBap KMcnoTa, 0yMapoBap KMC/ioTa, βμηηβρ KMcnoTa, JiMMOHHap KMcnoTa, 6eH30MHap KMcnoTa, κορμμηθρ KMcnoTa, MMHAanbHap mciīoTa, MeTaHcy/^OHOBap KMcnoTa, οτθ^πβΦοηοβθρ KMcnoTa, n-To/iyojicyr^o-ηοβθρ KucpoTa, cajimļMOOBap KMcnoTa μ.τ.π. Χοτρ a^p TpaHCAepManbHoro npMeMa neKapcTBa HecyuļecTBeHHO npMHMMaeTCP m OHO B OCHOBHOM MJ1M COneBOii φορΜβ, ΠρβΑΠΟΜΤΜΤβΛΒΗΟ, ST06bi ΟΑΗΟΒρβΜΘΗΗΟ C HMM (īpMHMMaJlCP reH-yCMJlMTeJ1b npOHMLļaeMOCTM KOJKMK) fljlP 3ΤΟΓΟ MOryT 6blTb MCnOJlb30B3Hbl HeKOTOpbie M3 ΜΗΟΓΜΧ n3BecTHbix reHOB-ycnpnTepeii npoHULļaeMOCTii ko>km. llpMMepaMM ποαχοααιαμχ reHOB-ycn/iMTe/ieii pb/ipiotcp AHMeTM/icy/^OKCMA (DMSO), ΑΜΜΘΤΜΓίφορΜβΜΜΑ (βΜΦ), Ν,Ν-ΑΜΜβΤΜ/ΙβΑΘΤΘΜΜΑ (DMA), ΑΘΜΜΠΜΘΤΜΙΊ-cyr^OKCMA (CioMSO), MOHOJiaypaT ποπΜ3ΤΜΠβΗ-Γ/ΐΜκοπρ (PEGML), MOHo/iaypaT mmļepnHa, sTaHoii, 3BKaJinmOBbiM cnupT, neiļHTHH, 1-H-AOAenmiAMKjia3ai4mcnorenTaH-2-oHbi (n3BecTHbie ποα Toproeoii MapKofl AZCH, KOMnaHMU Nelson Research & Development, Mpbmh, LJemp. AMepuKa) m MOHOJiaypaT προπΜ/ιβΗΓχίΜκοίΐΡ (PGML). 0co6eHHO npeAnoHTmejibHbiMM reHaMM-ycMJiMTe/iPMM npoHMiļa-
eMOCTH ΚΟΧΟΊ βΠϋ MCnOJ1b30BaHMP MX B ΟΟΗβΤ3ΗΜΜ C TpaHCAepMa/lbHblM ΓφΜΘΜΟΜ AeKCMeTOMMAHHa PBJIPKJTCP 3φΜρΝ, φορί^Πω [CH3(CH2)mC02]nR. b κοτορορ m PB/ipeTCP LļenbīM mmcpom, hmbioiaum 3HaneHne ot 8 ao 16, n paBHO 1 V\m 2, a R PBPPeTCP Hkl3llJMM aJIKM/lbHblM (C1-C3) OCTaTKOM, TO eCTb 3φΜρ ΗΘ33ΜβΙΑβΗΗωίί MJ1M 33ΜβΙ1(βΗΗΝΡ OAHOM MJ1M AByMP rMAPOKCM/lbHblMM rpynnaMn. B npeAnoMTmeribHOM BapnaHTe npMBOAUMoro 3Aecb OCyUļeCTBJieHMP Μ3θ6ρβΤβΗΜΡ ΟφΜρΗΒΐίί ΚΟΜΠΟΗβΗΤ ΠρβΑΟΤβΒΡΡβΤ co6oft HM3UJHM ariKMii (C1-C3) JiaypaT, (το ecTb m paBHO 10, a n paBHO 1), a b oco6o npeAnoHTMTePbHOM cnyMae oh npeACTaBPPeT co6oR "PGML" mpm "npormneHmnKonbMOHonaypaT". Cnei4napncTy b AaHHOū o6nacTM ποηρτηο, hto κοΜΜβρΜβοκΜΜ npoAyKT, npoAaeaeMbiM KaK "PGML", πρβΑοτθΒ/ΐΡβτ co6om TnnnMHyio cMecb caMoro nponnpeHmnKOPbMOHonaypaTa c nponMJieH-rnnKOJibAnnaypaTOM v\ jim6o c nponupeHmuKoneM v\ MeTnrmaypaTOM, nn6o c 5 ΟβΟΜΜΙΙ. TaKMM 06pa30M, ΤβρΜΜΗ "PGML" ΜΠΜ "πρΟΠΜΠΘΗΓ/ΙΜΚΟΠόΜΟΗΟ-jiaypaT” iicnonb3yeMbiū 3/ļecb, oxeaTbiBaeT κβκ MiicToe coeAMHeHiie, τθκ m CMecb, nonysaeMyio τθχηοπογμμθοκμ. Mcnonb3yeMoe 3flecb "3φφβκτιΐΒΗ0β" κοπμμθοτβο reHa-yciiniiTenfl npoHMLļaeMOCTH ko>km 03HasaeT κοπμμθοτβο, κοτοροβ o6ecneHMT ηθο6χοαμμοθ ποβωιηβΗΐιβ npoHMLļaeMocTM ko>km, ii, οοοτβθτοτβθηηο, Heo6xoflMMyK) rny6iiHy προΗίικΗΟΒβΗΐιη, HopMy npiieMa 11 KonMMecTBO noflaeaeMoro nerapcTBaio 06bNHO, b ρβμβπτγρβ fleKCMeTOMMflMHa, Hapflfly c reHOM-yciiniiTeneM npoHmļaeMOCTM κο>κιι, npncyrcTByioT ηοομτθπμ linu CBii3yuniie BeuļecTBa. TaKa κβκ ocHOBamie αθκομθτομμαμηθ ββχιαθτοβ TBepflbiM BeuļecTBOM, pņn TpaHCflepManbHoro npiieMa neKapcTBa ηθο6χοαμμ Kaxoti-iiM6o co/ifo6nnn3npyK)iiļnii areHT. 3iy ponb μο>κθτ BbinonHMTb Bbi6paHHbiii γθη-ycmimenb npoHULļaeMocTM κο>κιι; linu >κβ κροΜβ reHa-ycnmiTena npOHMLļaeMOCTM KO)KI1 ΜΟΜΘΤ npi1CyTCTB0B3Tb OflMH 11Π11 HeCKOJlbKO conto6nnii3iipyiouļiix θγθητοβ. Moiyr npncyTCTBoeaTb TaioKe flpyrne Hocmejin linu CBB3y»oiiļMe: θτοτ TepMiiH Βκπιοπββτ BeiiļecTBa-HOCMTenM, κοτοροβ o6biMHo npMMeHBKDTCB fljifi TpaHCAepManbHoro npkieMa neKapcTBa II KOTOpbie «BJIBJOTCB HeTOKCMMHbIMM 11 Ηβ 833ΜΜΟΑβΜCTByiOT C APy™MM ΚΟΜΠΟΗΘΗΤΘΜΙΙ Κ0ΜΠ03Ι4Ι4ΜΙ1, pa3pyUJafl Ι1Χ. npilMepaMM HCnOJ1b3yeMblX 3flecb noAXOA$uiļiix HociiTeneii 11 cBB3yioiAMX BBnneTCB BOfla, MMHepanbHoe Macno, cuniiKOHbi, >Kii/ļKiie caxapa, bockii, Ba3eniiH n Apyrne Macna h noiuiMepHbie MaTepiianbī.
TepaneBTimecKan ciicTeMa pj\f\ TpaHCflepManbHoro nptieMa fleKCMeTOMUfliiHa b οοοτβθτοτβμιι co cnoco6oM ιΐ3θ6ρβτβΗΐΐΡ npeACTaenneT co6oii MHorocnoftHbiM Κ0ΜΠ03Ι1Τ, npeACTaBneHHbiii Ha pncyHKax 1 u 2. yCTpoCĪCTBO (1) ΒΚΠΙΟΜΘΘΤ: (a) M3HaH04Hblii Cnoii, KOTOpblM Cny)KI1T B KanecTBe ΒβρχΗβϋ ποΒβρχΗοοτιι M3,qeniifl (10); (b) Heo6«3aTe/ibHo CKpennflfOLiļMfi aflre3MBHbiii cnoii (11), npiiMbiKaioiiļiiM κ H3HaH0HH0My cnoio; n (c) KOHTaKTHbiii aAre3iiBHbift cnoii (12), KOTopbiū npeACTaenaeT co6oft ocHOBHyra noBepxHocTb ycTpoficTBa n κοτορωϋ KOHTaKTMpyeT m npuKpenrmeTca κ κο>κθ b npoLļecce ncnonb30BamiR npeflnoMTiiTe/ibHbiM BBAseTCB TaioKe, mo6bi κομπο3Ιιτ coflep>Kari (d) - Heo6«3aTenbHo -nopucTbiCi npoMejK^oMHbiii cnoii (13) Me>Kfly CKpennniomiiM ιι κοητθκτηημ aflre3iiBHbiM crioeM, xyfla βκπιομθη CKpennnioiiļMii cno ii, - stot npOMe>KyTOMHblM cnoii o6bMHO rOTOBMTCB 113 aflCOp6eHTHOrO ΗΘΤΚ3ΗΟΓΟ MaTepiiana. Ilocne naMiiHiipoBaHiiB CKpennntoLHiiii aflre3MB h KOHTaKTHbiii aflre3iiB npocaMiiBaioTCB b npoMe>KyTOHHbiii cnoii c o6pa30BamieM Κ0ΜΠΟ311ΤΗ0Γ0 CJlOfl (14), ΒβρΧΗΒΒ MaCTb ΚΟΤΟρΟΓΟ (15) COflep>KMT npoMe>KyTOHHbiM cnoii n οκρβπηηκΐΐΑίιϋ a/ļre3MB, a HiDKHnn nacTb (16) -npoMe>KyTOHHbiū cnoū m KOHTaKTHbiū aflre3MB. B ynaKoeaHHOM Biifle, ao npiieMa, ycTpoūcTBO - x<enaTenbHO, flon>KHO TaioKe BKnioHaTb CBo6oflHbiū BKnaflbiuj (17), npuneraiouļiiū κ BHeujH6My KOHTaKTHOMy cnoio ποβθρχηοοτμ. M3HaHOHHbiū cnoū BbinonHneT φyHκ^n^o rnaBHoro CTpyiaypHoro aneMeHTa ycTpoūcTBa m coo6maeT ycTpoūcTBy 6onbUjyio nacTb ero rn6K0CTM, ποΑΧΟΑηίΑΘϋ cnocoāHOCTii κ "oāneraHiiio" 11, ecnii θτο ηθο6χοαμμο, οκκηκ>3ΐΐΒΗθοτιι. H3HaHOMHbiū cnoū Mo>KeT cny)KiiTb TaioKe b KanecTBe 3amiiTHoro noRpbieaiomero cnon pj\?\ npeAOTBpameHiin noTepii neKapcTBa ii/nnn Ηοαιτβηη nyTeM ero nepexoAa Mepea ΒβρχΗίοιο noBepxHOCTb ii3Aennn. M3HaHOMHbiū cnoū Μθ>κβτ ucnonb30BaTbcn απβ npiiAaHMB ιΐ3Αβηιικ) οπρβΑβηβΗΗοϋ crenemi okioik)3iibhoctii, τθκ κβκ πριι 6 LV 10685 annriMKaLļMM Ha κο>κγ nnomapb noKpbieaeMOM ko>km CTaHOBUTcn rkiApaTMpoBaHHoii. H3HaHOHHbiM cnofi iotobmtch npeflnoHTMTenbHO m mcra mam nneHKM npenMyuļecTBeHHO γμΟκογο anacTMHHoro MaTepnana, KOTopbiū nenneTca 3HaMmenbHO HenpoHMLļaeMbiM α©κομθτομμαμη3. npeAnoMTMTenbHO cnofi μμθθτ τοπιαμηυ noop^AKa ot 0,0005x2,254 cm ao 0,003x2,54 cm μ Μθ>κβτ 6biTb Heo6fl3aienbHO πμγμθητμροβθη, MeTannn30BaH mam noeepxHOCTb ero Μθ>κβτ 6biTb MarmpoBaHa απ« HanMcaHMA. npeAnoMTUTeiibHO cnoii iotobmtca m τθκογο MaTepnana, KOTopbiii πο3Βοη«θτ M3Aennto no>KMTbcn Ha KOHTypy ko>kh, 6biTb KOH<ļ>opTa6enbHbiM b HOCKe, τβκ, hto6w Ha yMacTKax κο>κη, κοτορωβ oābNHo noABep>KeHbi μθχθημμθοκμμ Hanp«>KeHMAM - cyciaBbi mam Apyrne MecTa crn6oB - Bepo^THOCTb oTCTaBaHMfi H3flennH ot koku 6bina 6bi MMHMManbHofi n3-3a HeOonbLiiofi pa3HHLļbi b γμ6κοοτμ m anacTMHHOCTH Me>KAy μ3Αθαμθμ m KOMeft. llpuMepaMM anacTOMepHbix nonHMepoB, npnroAHbix απ& n3roTOBneHvw μ3Η3Ηομηογο cnoa, flenmoTcn . δηοκ-ποηΜΜβρω nonn3TnneHaMMAa, TaKHe, κβκ ΡΕΒΑΧ-ποπΜΜβρω, δηοκ-nonnMepbi nonn3TnneHMeTnnMeTaKpnnaia (EMA) τθκμθ, κθκ NUKREZZ-nonMMepbi, nonnypeTaHb», TaKHe, xax PELLATHANE- mam ESTANE-nonHMepbi, CHHHKOHOBbie SfiaCTOMepbl, nonH3<£npHbie 6nOK-nonHMepbl, COCTOflLLļMe M3 TBepAblX Μ ΜΑΓΚΜΧ ΟΘΓΜΘΗΤΟΒ (HanpMMep, HVTREZ-nOAMMepbl), ΡΘ3ΜΗΟ-ποΑοδΗΒΐϋ nonnn3o6yTnneH, CTHpon h cTnpon6yTaAneHOBbie m CTnponnonnM3onpeHOBbie cononmviepbi. Γμ6κμθ nonHMepbi BīcntonaioT ποαμθτμαθη, ποαμπροπμαθη, ποηΜΘφΜρω (HanpMMep, ποπΜβφΜρτθρβφτβηθτ, "PET") H.T.n., KOTopbie MoryT Mcnonb30BaTbCfl κβκ b BHpe πηβΗοκ, τθκ m naMMHaTOB. Ucnonb30BaHne KOHKpeTHoro nonMMepa aah μ3Η3ηομηογο cnoa 33BHCHT ot MaTepna/ia, BxoAniiļero b mflenue, Bicmonan HOCHTenb, conto6nnn3npyK)U4Mii areHT, reH-ycnnnTenb npoHHLļaeMocTH m t.a. npeAnoHTHTenbHO npepnameMbifi γη6κηη M3HaHO*-iHbifi MaTepnan npeACTaenneT co6ofi 0,0254 mm πon^ι^φ^1pHyκ) nneHicy c MaTTMpoBaHHofi οδρβδοτκοίί noBepxHocTn, npnroAHyio pj\n η3απμομ, nocTaBnneMyio φιιρΜ3ΜΜ Du Pont (Mylar) m ICI Americas Inc. (Melinex). ,CļpyrnM npeAnoHTMTenbHbiM MaTepnanoM nenņeTcn MeTannM3MpoBaHHbifi nonu3φΜρ (3M N&1109). Unu >xe npeAnaraeMbifi M3HaHOHHbifi MaTepuan npeACTaBnneT co6ofi npo3paHHbiū ποηιιοφΗρ (3M Ne 139).
KpennaļMft cnofi Heo6«3aTenbHO ajerinneTcn c M3HaHOMHbiM m KOHTaKTHbIM ΟΠΟΘΜ. B HaCTHOCTM, ΓφΜ Μ3ΙΌΤΟΒΑΘΗΜΜ yCTpofiCTBa ΚρβΠΑ111βΓΟ cnon Hcnonb3yiOT ycnnnTenn npoHMiļaeMOCTM, a ycnnnTenb 6yAeT CnOCOOCTBOBaTb pa3AeneHHIO M3H3HOM HOrO H ΚΟΗΤΘΚΤΗΟΓΟ aAre3MBHbtx cnoee. KpenfliiļHM aAre3MB αοπ>κθη 6biTb οοβμθοτμμ c αβκομθτομηαηηομ m c πρμμθηαθμμμ HocHTeneM. ripeAnonaraeTcn, ητο αθκομθτομμαμη μμθθτ HM3Kyio pacTBopMMOCTb b κρβπηιμβΜ cnoe m οοο6θηηο, mto oh ηθ nepexoAHn 3HaMMTenbH0 M3 κοητ3κτηογο cnoii b KpennuļMŪ cnoū. Οοοτβθτοτβθηηο, KOHKpeTHbIM 8ΑΓβ3ΜΒ, Bbl6paHHblM A^^ ΚρβΠ5>111ΘΓΟ ΟΠΟΡ, 6yAeT M3CTMMH0 3aBMceTb ot κοητθκτηογο cnon κομπο3μαμμ m MaTepnana, BbiOpaHHoro Rnn Μ3Η3ΗΟΗΗΟΓΟ CnOfl, M HaCTMHHO OT OTHOCMTenbHOrO ΚΟΟφφΜμΜΘΗΤβ pacnpeAeneHMjļ Me>KAy κοητθκτηημ μ κρβπηιμΜΜ οποβμμ. Ποαχοα^ιαμμμ aAresMBaMM a^^ Kpennu^ero cnon nenmoTcn nonncnnoKcaHbi, nonMM3o6yTMneHbi, ηοηΜθκρΜηβτω, nonMypeTaHbi, πη30ΤΜφΜΐ1ΜροΒ3ΗΗΗθ 3TMneH-BMHMnai4eTaTHbie cononMMepbi, HM3KOMoneKynnpHbie δηοκ-nonMMepbl Π0ηΜ3φΜρ3ΜΜΑ0Β (Η3ΠρΜΜθρ, ΡΕΒΑΧ), KneŪKMe KayMyKM, Τ3ΚΜΘ, 7
Kax nojiMM3o6yTMneHOBbie, nonMCTMpon-M3onpeHOBbie cononuMepbi, nonncTnpoji-6yTaflneHOBbie cononiiMepbi μ ιιχ cMecii. ΠρβΑηο>ΚΘΗΗΝβ 3flecb KpenfliiļMe a/ļre3MBbi npe/ļCTaBnaioT co6oft nonwi3o6yTMneHbi, aKptinaTbi m CMDMKOHbl, OCOāeHHO ΠΟ/1 MM306yTMJieHbl. KpenflLlļMii CilOM 06bMH0 ΜΜΘΘΤ
TonuļMHy ot 10 flo 75 ΜΜκροΜβτροΒ (0,001 - 0,075 mm), npeflnoMTUTenbHO OKOJIO 50 ΜΜκροΜβτροΒ 2x0,0254 MM. 06blHHO OH flOJOKeH 6blTb TOHbUJe, ΗβΜ KOHTaKTHbiM aflre3MBHb)M cnoii: 3to noMoraeT οβθοτμ flo MMHMMyMa KonunecTBo neKapcTBa, npoiuefliuee b KpenniuMfi cnoii.
KoHTaKTHbiii aflre3MB npe/ļCTaBnneT co6oii HyBCTBMTenbHbiū κ flaBJieHmo aflresnB, ποαχοαηι^μμ ann λοπγοβρθμθηηογο κοητθκτθ c κο>κθμ.
Oh βΟΠ)ΚΘΗ 6blTb TaiOKe φΐ13ΜΜΘΟΚΜ M ΧΜΜΜΗΘΟΟΙ COBMeCTMM c fleKCMeTOMMflMHOM M npilMeHfieMbIMM HOCMTeJlflMlI II CBfl3yUļMMI1K) flanee, neKapcTBO αογοκηο 6biTb flo Ηβκοτοροϋ οτθπθημ pacTBopiiMo b aare3MBe, Tax, HTo6bi oho ηθ nepexoflMno b Kpen^nļiiM cnoii (ηθ yfla/ifl/iocb c ko>km), a flon>KHO npoHiiKaTb b Kox<y. Maiepnan TaiOKe αο/ιμθη μμθτί» BbicoKiiii Κ03φφΜψ1βΗΤ fl^1φφy3^1^1 AJlfl fleKCMeTOMMfllIHa. KOHTaKTHbliī cnoii o6blHHO ΜΜβΘΤ TOmiļMHy npM6nM3MTenbHO OT 10 flO 100 ΜΜκροΜβτροΒ (0,01 - 0,1 mm), npeflnoHTMTenbHo οκοηο 75 ΜΜκροΜβτροΒ (0,075 mm). Ποαχοαηιμμθ aflre3MBbi βκπ(0Μ3Κ)τ noniicMnoKcaHbi, nonMM3o6yTMneHbi, noniiaKpMnaTbi, nonnypeTaHbi, πηθοτΜφΜμιιροΒβΗΗΝβ 3TM/ieH-BMHiinai4eTaTHbie cononiiMepbi, βηοκ-ποηιίΜβρω ποηΜοφΜρβΜΜ^οΒ ημ3κογο Mone«ynnpHoro eeca (HanpiiMep, ΡΕΒΑΧ), κπθΗκμθ KaynyKM, eaKiie, xax nonmi3o6yTMneH, nonMCTMpon-M3onpeHOBbie cononMMepbi m mx cMecM. ripeflnoMTMTenbHbiMM KOHTaKTHbiMM a,qre3MBaMM ceMHac ηβηηιοτοη aKpunaTbi, cMnMKOHbi m nonMypeTaHbi. ripoMe)KyTOMHbiM cnoPi npeflCTaenaeT co6ofi τοηκμμ γμ6κμμ aflcopāeHTHbiii cnoii, κοτορωϋ cny>KMT απη MMMo6MnM3ai4MM xax κρβπηιμβΓΟ, τβκ μ κοητθκτηογο cnon, npeflOTBpaman CMopuļMBaHMe, paccnaMBaHMe m χοηοβΗοβ τθηθημθ coāpaHHoro M3,qenMfl. llpeflnoHTMTenbHo, ho ηθ a6coniOTHo ηθο6χοαμμο, BKmonaTb npoMe>KyTOHHbiM cnofi. Προμθ^τοηηημ cnoii BKmonaeTCB TonbKO b τθ M3flennn, κοτορωθ coflep>xaT κρβπηιι^ΜΜ cnoii. B npoLļecce M3roTOBneHMB M3,qenMR KpennuļMŪ aflre3MB μ κοητθκτηνμ aflre3MB MMrpMpyeT b npoMex<yTOHHbiū cnoii, coeflMHnncb b ηθμ. l1poMe>KyTOHHbiM cnoii flon>xeH 6biTb nonHOCTbio npoHMLļaeM flnn ecex κομποηθητοβ M3flenMfl, m TaKMM o6pa30M, ηθ ,qon>KeH MrpaTb ponb orpaHMHMBaiouļeū CKopocTb MeM6paHbi. Cnoū npeflnoHTMTenbHo M3roTaBnMBaeTcn M3 ηθτκθηηογο MaTepnana, τθκογο, xax ποηΜβφΜρ, ποηΜ3ΤΜηβΗ, ποηΜπροπΜηβΗ, nonMaMMflbi, BMCK03a vim χηοποκ, οοο6θηηο 100%-HblŪ H6TKaHHblŪ ΠΟηΜθφΜρ. HjlM >ΚΘ MOryT 6blTb ΠρΜΜΘΗΘΗΝ ΤΚβΗΗΘ M3flenMB, HO OHM ΜΘΗΘΘ npeflnOMTMTenbHbl. npOMe>KyTOHHblŪ cnoū oGbMHO μμθθτ TonuļMpy ot 0,0254 flo 0,254 mm. CBo6oflHaa npoKnaflKa (BKnaflbiiu) npeflCTaBnneT co6oū yflanneMbiii sneMeHT, κοτορωϋ cny>KMT TonbKO flnn 3aiflMTbi M3flenMfl flo ero Hano>KeHMn. 06νμηο, cBoāoflHaa npoKnaflKa γοτοβμτοα M3 MaTepnana, HenpoHMflaeMoro flnn neKapcTBa, HOCMTenn m aflre3MBOB, oHa nerxo οημμθθτοβ c κοητθκτηογο aflre3MBa. CBo6oflHbie npoīcnaflKM o6bNHO o6pa6aTbiBa>OTCB cmtimkohom linu φτopyΓnepoflaMM. B HacTomiļee BpeMn npeflnoHTMTenbHbiM «enneTcn Mcnonb30BaHMe ποκρωτοΓΟ cmtimkohom ΠΟΠΜθφΐΐρθ.
OSbNHO, M3flenMe Μ3ο6ρθτθημα γοτοβμτοα c Mcnonb30BaHMeM cnoco6oe, CTaHflapTHbix b αθηηομ o6nacTM - οτηΜΒΚοϋ nneHKM nyTeM 8 LV 10685
McnapeHMR pacTBopmenfl, jiaMUHMpoBaHueM tohkom ππθηκκ m Bbipy6HOM ιυτβΜποΒκοϋ. npefl/iaraeMoe 3,qecb ocymecTBJieHi4e μ3ο6ρθτθημη npoM3BOflMTcn cneflyK)UjļMM o6pa30M: Γotobhtca pacTBop fleyx coeflMHeHHbix nojiMMepoB BMHunaLļeTaT-aKpunaTa b oTunaL^eiaTe, Tonyone (mjim M3onponaHone) μ θτθηοπθ B3BeiiiHBaHneM Kax<Aoro pacTBopa nonuMep/pacTBopuTejib b cooTBeTCTByiouļeM cocyfle m nocne^romnM cMeiueHMeM nx flo paBHOMepHOTO ΓΟΜΟΓΘΗΗΟΓΟ COCTOBHMfl - απη oāpaaoeaHtifl pacTBopa, npeAHa3HaMeHHoro ρ,ηη κοητθκτηογο cjiob, Ecjim ηθο6χοαμμο, μο>κηο 3aM6HMTb aAre3MB, no/iyMeHHbiM Ha ocHoee boahom 3MyjibCMM aKpunaia, Ha pacTBop, coAep>KaiAMii pacTeopmenb. floOaenfleTCfl ηθο6χοαμμοθ KOJiMMecTBo AeKCMeTOMMAMHa m ece TiiļaTenbHo nepeMeuMBaeTCfl. Ha stom 3Tane Ao6aBJiaeTC - Heo6«3aTejibHo - reH-ycunnTejib (HanpiiMep, PGML). 3aTeM, roTOBMTCB pacTBop nojii4i43o6yTMneHOBoro m nonn6yTnneHOBoro ΠΟΠΜΜβρΟΒ B reKCaHe B3B6LUl4BaHM6M nojiMMepoB M reKCaHa B ΟΟΟΤΒβΤ-CTByK)UļeM COCyAe Μ ΟΜβΙΙΙΘΗΜΘΜ Ι4Χ AO paBHOMepHOrO 14 ΓΟΜΟΓΘΗΗΟΓΟ coctohhhh c o6pa3oeaHi4eM pacTBopa pj\a otjimbkm CKperuiHiouļero cnofl. 3aTeM, pacTBop ρμη cKpennmoiiļero aAre3HBa πρΜκρβπχΐΗΘΤοΗ κ Heo6pa6oTaHHOH οτοροΗβ cbo6oahoh npoīcnaAKH c Mcnonb30BaHneM ΤΘΧΗΟΠΟΓΜΜ: 3KCTpy3HOHHOrO npeCCOBaHHH, o6pa30BaHI4H nOKpbITHfl c noMoiiļbio paicejifl mjim βθπμκοβογο ποκρωτΜΗ. Γθκοβηοβμη pacTBopmenb yAaiineTCH nponycKaHneM ποκρωτΜΗ nepe3 cyuiH/ibHyio nenb. 3aTeM, M3HaHOMHblH CJlOft ΠρΜΚρβΠΠΡΙΘΤΟΗ B Β14ΑΘ JlHCTa K BbiCyUieHHOMy CKpenjiHioiiļeMy aAre3HBy c coxpaHenneM paBHOMepHoro αββπθημη Banma. 3aīeM ceoOoAHaH npoīcnaAKa CHHMaeTCfl (nonocon) v\ Ha ee μθοτο npHKpennneTCH nneHKa 143 ηθτκθηηογο βο/ιοκηθ - npn paBHOMepHOM AaeneHHH eana. l1onyHaK)iAHHCH πθμμηθτ ηθμθτβιβθθτολ Ha ponm. 3aTeM, pacTBop - neKapcTBo/KOHTaKTHbiM aAre3i4B - ηθηοομτοη Ha CBo6oAHyio npoicnaAKy, a pacTBopHTenb yAa/i«eTCH nponycKaHneM cnon Hepe3 cyunuibHyto nenb. nocne 3τογο, npH paBHOMepHOM αββπθημκ eana, npOM3BOAMTCH ΠρΜΙφΘΠ.ΠΘΗ14Θ BblCyiūeHHOrO ΚΟΗΤβΚΤΗΟΓΟ CflOH K B0J10KHI4CT0M ΠΟΒΘρΧΗΟΟΤΗ Χ13ΜΜΗ3Τ3: M3HaHOHHblĪ4 CJlOH/CKpenJIHlOLAllPi CJlOft/BOJlOKHMCTblii CJIOH, AOnyCKaH npH 3T0M ΠΘρβΤΘΚ8ΗΙ4Θ KpenflLlļerO H Κ0ΗΤ3ΚΤΗ0Γ0 3ΑΓΘ314ΒΟΒ B npOMe)KyTOHHblii BOfiOKHHCTblH CJIOH. HaKOHeLļ, jiaMHHaT pa3pe3aeTca Bbipy6HbiM uiTaMnoM Ha oTAenbHbie H3Aenna, npoBepaeTCB h ynaKOBbiBaeTca b πθκθτν, 3anai4BaeMbte nocpeflCTBOM o6orpeea. 9 npuMeDbi. npeflCTaBJieHHbie ημ>κθ npMMepbi npe^CTaBnaraT co6om AanbHeMiuee pyKOBOflCTBO A/ifl cneLļiia/nicTOB b flaHHOM o6nacTM m hm komm oSpaaoM He MoryT paccMaTpueaTbca κβκ ογρθημμμββιοιαμθ μ3ο6ρθτθημθ. Πρμμθρ 1 ycTpoiicTBo M3roTOBriflJiocb cneAyK>mnM o6pa30M:
KoHTaKTHbiii aflre3MBHbiM cnoii ΓοτοΒΜ/icfl CMeuueHMeM αβομηογο nonMMepa BMHMnaLļeTaT-aKpunaTa (18,84% Gelva 737 m 75,36% Gelva 788) c MOHOJiaypaTOM προπμ/ιθηγ/ιμκοπα (PGML, 4,96%, nonyHeHHbiM ot Gatefesse) μ αθκομθτομμαμηομ (0,84%, b βμαθ οβο6οαηογο ocHOBaHun, nonyMeHHbiM ot Farmos) m nepeMeiuMBaHMeM μχ b τθμθημθ 24 Macoe Ha Bn6pnpy(oinnx Ba/ibiļax M3 ηθρχοβθιοιαθμ ciānu flo αο^τμ>κθημη OflHOpOflHOCTH Μ ΓΟΜΟΓΘΗΗΟΟΤΜ. Κοηθηηνμ pacTBop omneancn Ha 3x0,0254 mm cbo6oahom nnomaAKe H3 CMnMKOHH3MpoBaHHoro ποπΜΘφΐφθ (Polyslik®, HP Smith). OinmoMy pacTBopy npHflaBanM TOHHyio TonuļMHy b 10x0,0254 mm (ToniLļMHa, npeflLnecTByK)inafl cyuuKe) c ncnonb30BaHneM pņn o6pa30BaHM« ποκρωτΜη pyHHoro pa«enn Gardner. Ilocne θτογο, pacTBopmenn yflan«ioTcn BbicyujMBaHneM οτηΜτοϋ πηβΗΚΜ b cyujnnbHoii πθημ πρπ 65 °C b τθηθημθ 20 MHHyT. CKpennniOLLļMH aAre3MBHbifi cnoii roTOBMncn ομθιιιθημθμ nonn6ymneH/nonnM3o6yTnneHOB (4,50% Vistanex L-100 PJB m 22,50% Vistanex LM-MS-SC PJB, nonyMeHHbtx οτ Εχχοη) c nonn6yTnneHOBbiM icneeM (9,00% Indopol H1900 PB, nonyMeHHbiM οτ Ameco) m reKcaHOM (64%). CMecb nepeMeuiMBanacb β τθμθημθ 60 Macoe flo paBHOMepHoro ΓΟΜΟΓΘΗΗΟΓΟ COCTORHMR. rionyMaK)L4HHCR pacTBop OTnMBanca Ha (3x0,0254 mm) cbo6oahom nnoaļaAKe H3 cnnMKOHH3npoBaHHoro ποηΜΘφΜρβ (Polyslik®, HP Smith). OTAMTOMy pacTBopy npMAaiOT TOHHyio TonmMHy 5 aiommob (5x0,0254 mm) (ToniiļHHa, npeALuecTByHDLLļan cyuiKe) c Mcnonb3oeaHMeM Ana o6pa3oeaHMa noKpbiTHfl pyHHoro paKenn Gardner, a pacTBopnTenn yAann>OT cyuJKOH οτηΜΤοϋ πηβΗΚΜ b cyujMnbHofi πθμμ πρπ 65 °C β τθηθημθ 20 MMHyT. 3aTeM, M3HaHOHHbiii cnoii naMMHMpyeTca Ha BbicyweHHbiM CKpennnioiAMtf aAre3MBHbifi cnoii, ceo6oAHan npoioiaAKa yAanaeTC« m npMKnaAbiBaeTcn npoMe>KyTOHHbiM BonoKHMCTbiM cnoii (Reemay 2250). rionyHaK)LLļMMCR npoAyxT HacnaMBanca Ha κοητθκτηημ aAre3MBHbiM cnoii npM ocyiiļecTBneHMM pyHHoro AaeneHMn Ha BanMK, αοογθτομηογο απη τογο HTo6bi, HTOČbl 3aCT3BMTb ΚρΘΠΗίί|ΜΜ 3ΑΓΘ3ΜΒ M KOHTaKTHbIM 3ΑΓΘ3ΜΒ ΒΟΜΤΜ B conpKOCHOB6Hne b npeAenax cTpyicrypHoro cnoa c o6pa30BaHMeM κοηθμηογο naMMHaTa. 3θτθμ naMMHaT pa3pe3anca Ha npaMoyronbHMKM 20 cm2 c 3aKpyrneHHbiMM yronKaMM, MapKMpoeanca m 3ananBancR b nneHOHHbie MeUJOHKM. 10 LV 10685 ΠρυΜβρ 2 (OnpefleneHMe BbifleneHMfl in vitro) flepMaTOMMpoBaHHbiii flepMMC.ariMflepMMC (oTTorpHyTbiii pna κο>κηομ TpaHcnnaHTaLļnn) 6bin πο/ιγΜβΗ 113 ο>κογοβομ κπμημκμ. 06pa3iļbi nonyHanncb OXTia)KfleHHblMM nnn 3aMOpO>KeHHbtMM (COXpaHfleMblMM B >KMflKOM a30Te). Bce o6pa3iļbi po ncno/ib30BaHMfl 3aMopa>KiiBanMCb npw - 20 °C. 3nn,qepMMC CHMMajicn c aepMMca pyMHWM cnocoOoM nocne HarpeBaHua b BOfle npn 60 °C B ΤΘΜΘΗΜβ 2 MMHyT. SnMflepMMC ΠΟΜβίμβ/ΙΜ Ha ΠΟΒβρΧΗΟΟΤΒ BOflbl, 33ΤΘΜ BbiHMManM m yKnaflbiBann cnoeM Me>Kfly flByM« cjioamm π/ιθηκμ M3 aiļeTaia Lļe/uiiojicttbi. 3tm npenaoaTbi ncno/ib30Bajincb cpa3y we mv\ 3aMopa>KHBanMCb pj\n τογο, πτο6ω Mcno/ib3oeaTb no3flHee.
HcnbiTyeMbie \\pvs\apm roTOBu/rncb c ncno/ib30BaHneM c/ieflyK)iiļMX peiļemyp: A: Cm"inKOHOBbiPi KOHTaKTHbiū aAre3MB: Dow Corning 2920; ΑβκοΜβτοΜΜΑΗΗΟΒΟβ ocHoeaHMe: 1,8-2,2% (MHTepean cyxofi Harpy3KM = 0,5-3,0%); PGML: 8%; ΠοπΜΘφΜρΗΒίΜ HeTKaHbiū c/ioft: Reemay 2250, CKpen/iJuoiiļMM cjiom: norMM3o6ymneHOBa;i CMecb, M3HaHKa: 0,5x0,0254 mm npo3paHHbiM πο/ΐΜοφκρ (3M Ns139). B: AKpu/ioBbift κοΗτβκτΗωίί aflre3MB: CMecb Monsanto Gelva 737 m 788; fleKCMeTOMMflMHOBoe ocHoeaHMe: 1,8-2,2%; PGML: 8%; rionnacjDMpHbiM HeTKaHbiii c/ιοίί: Reemay 2250, CKpenjiflfOLLļnii cnofi: nonnn3o6yTnneH, n3HaHKa: 0,5-fliOMMOBbiii 0,5x0,0254 mm Π0ΠΜ3φΜρ. C: ΑκρΜηοΒωίί Komaicmbifl aflre3MB: CMecb Gelva 737/788; ΑβκοΜβτοΜΜΑΜΗΟΒΟβ οοηοβ3ημθ: 1,8-2,2%; PGML: 12%; ΠοηΜθφΜρΗωίί HeTKaHbiPi c/ioii: Reemay 2250, cKpenn«tou4nfi cnofi: nonnn3o6yTnneH, M3HaHKa: 0,5x0,0254 mm npo3paMHbift πο.πΜ3φΜρ (3M Ns139). D: CminKOHOBbifi κοητθκτηνμ aflre3HB: Dow Corning 2920; ΑβκοΜβτοΜΜ^ΜΗΟΒΟβ ocHOBaHi/ie: 1,8-2,2% (MHTepBan cyxo(i Harpy3KM = 0,5-3,0%); PGML: 8%;
HeT npoMe>KyTOHHoro cjioh,
KpenmiļMM cnotf: nonnM3o6yTM/ieHOBaii CMecb, M3HaHKa: 0,5x0,0254 mm ποπΜΘφι/ιρ (3M Ne139). E: AKpmioBbiii κοητθκτηημ aflre3MB: Gelva 737/788-CMecb; fleKCMeTOMMflMHOBoe ocHOBaHiie: 1,8-2,2%; PGML: 12%; Ηβτ npoMe>KyTOHHoro cnoa, 11
Kperminkiii cnofi: nonnM3o6yTmieHOBafl CMecb, M3HaHKa: 0,5x0,0254 mm ποπμθΦμρ (3M Ns139). H3 annflepMa/ibHbix npenapaioe c Mcnonb30BaHneM LirraMna Arch Bbipe3anncb xpyrn κοχαι, noMema/incb Ha noeepxHocTb boan, BbicytuMBanMCb προμοκθημθμ Ha πηβΗκβ M3 aLļeTaia L^enniono3bi npw προββρκθ Ha npocaHHBaeMocTb. HaKnaflKM, npnroTOBneHHbie xax 6bi/io onucaHo Bbiiue, Bbipe3a/iHCb KpyraMM τβχ >κθ paaMepoe h cocnanBajincb c KOKHbiMM npenapaiaMH (no τρΗ Ha Kaxcfly»o peiļeriTypy). 3aTeM «ax<flbiM naMHHaT noMeiiļancn b βθρχηθη nacTH μ3γοτοβπθηηογο pyHHbiM cnocoāoM flHφφy3MOHHOΓO ΗΜΘΜΗΗΟΓΟ ΟΤΒβρΟΤΜΡ - ΠΟ TMny ΑΜφ^3ΜΟΗΗΟΗ ΒΜβίίΚΜ Franz (ropM30HTaxibHan nnocKocTb ko>kh) m 3aKpennnncn. 3ia nneHKa MMena o6~beM pe3epeyapa 7,5 mji, fl^1φφy3HOHHy^o nnoiiļaflb 0,689 cm2 m OHa noflBepranacb HarpeeaHmo c Mcno/ib30BaHneM TepMocraTa - npn 32 °C. >KnflK0CTb b pe3epeyape npeflCTaenfma co6om μ3οτοηκηθοκμμ coneeoH pacTBop, 6yφφepnpoBaHHbι¢ί φοοφβτΗΝΜ 6yφφepoM - MMeiouļMM pH 5,0 m coflep>Kaii^MM 0,1% reHTaMHLļMHa. OO'beMbi o6pa3Lļoe cocTaBrmnn 1,0 mji, ohm Bbiflep>KHBanMCb b yKa3aHHbix ycnoBnnx b τθμθημθ 0,5; 1IO0; 1,5; 2,0; 4,5; 17,0; 21,0 m 25,5 Hacoe. KoHLļeHTpaiļiin fleKCMeTOMHflMHa onpe/ļermnacb μθτοαομ ΒωοοκοθφφβκτΜΒΗΟΜ jkhakocthoh χροΜβτοφβφΜΜ (B3>KX).
PncyHOK 3 flaeT KyMyn«THBHoe κο/ιμμθοτβο fleKCMeTOMHflHHa (b MHKporpaMMax/cM2), npoiueflLuee Mepe3 o6pa3iļbi ko>km nna Kamoli ρΘμΘπτγρω (KBaflpaTbi c tomkom = A, TeMHbie poMābi = B, ceembie KBaflpaTbi = C, CBeTJībie poMābi = D m TeMHbie KBaflpaTbi = E). noflCMmaHHbie BbifleneHHJi flaHbi b Ta6nmļe 1. ΤΑ5ΠΜΙ4Α 1
CpeAHMe BbiaejietiMfl PeLļenTypa BbifleneHMn (MMKPOrpaMMbl/CM2/HaC JlaTeHTHbiii nepnofl (nacbi) A 3,9 1,0 B 3,5 1,7 C 4,4 0,9 D 3,4 1,1 E 4,6 1,9 llpHBefleHHbie pe3ynbTaTbi noKa3biBa»OT, hto M3flenn« n3o6peTeHMH cnoco6HbinponycKaTb ΘφφΘΚΤΜΒΗωβ b TepaneBTMHecKOM οτΗουβΗΜΜ κο/inMecTBa fleKCMeTOMMflUHa nepe3 MenoBeHecKyro xox<y b onbuax in vitro. 12 LV 10685 ΦΟΡΜΥ/ΙΑ M30BPETEHMJ1 1. yctpoūctbo pj\a TpaHCAepManbHoro npneMa fleKCMeTOMU/ļMHa nepe3 npeABapme/ibHO onpefleneHHyK) nnouļaAb 3Aopoeoii κο>κμ, OTnunaiomeecfi τβΜ, hto oho BKntoMaeT: (a) M3HaHOMHblM Cnoii, KOTOpblfi ΟΠρΘΑβηΗΘΤ ΒβρΧΗΙΟΙΟ ΠΟΒβρΧΗΟση» M3Aennaμ (b) cnoii, MyBCTBMTenbHbiii κ /ļaeneHUK), φβρΜβΑθΒΤΜΜβοκΜ npnevmeMbiM κοητθκτηημ aAre3MBHbiii cnoii, ΜΜβιοιιμιϋ nnouļaAb, no cytAecTBy paBHyio η33Ββηηοη npeABapuTenbHoii nnouļaAM 3Aopoeoii κομοί, BKniOMaioiAHM Marepuan, κοτορωϋ nenne tca npoHtiqaeMbiM βηη Α©κομθτομμαμη3 μ otot cnoii npeACTaBfifleT ocHOBHyio noBepxHocTb yCTpOMCTBa, KOHTaKTMpyeT Μ ΠρΗΚρβΠΧΙΒβΤΟΒ Κ ΚΟ>ΚΘ ΠρΜ MCnonb30BaHMM ycTpoiicTBa1 β κοτοροΜ α©κομθτομμαμη pacnpeAenneTcn nepe3 Ha3BaHηνμ κοητθκτηημ aAre3idBHbin cnoii nocne ycTaHOBneHnn paBHOBecnn b Η33Β3ΗΗΟΜ Μ3Α©ηΜΜ. 2. ycTpoiicTBO no nyHKTy 1, OTnHnaioineecn τθμ, hto oho, κροΜβ τογο, Βκηιοπθβτ: (c) CKpennaiouļHM aAre3MBHbifi cnoii, pacnono>KeHHbiii Me>KAy KOHTaKTHbIM 3ΑΓΘ3ΜΒΗΒΙΜ ΟΊΟΘΜ M M3HaHOHHblM ΟΊΟΘΜ, H naMMHHpOBaHHblfi C HMM. 3. ycTpoūcTBO no n.2, OTnMHaiomeecfl τθμ, hto oho, κροΜΘ τογο, coAep>KMT: (d) nopncTbiū npoMe>KyTOHHbiti cnoii Me>KAy Ha3BaHHbiM CKpennfltooļHM aAre3MBHbiM cnoeM v\ κοητθκτηβιμ aAre3HBHbiM cnoeM, KOTopbiū nenneTcn npoHULļaeMbiM flrm fleKCMeTOMUflMHa. 4. ycTpoūcTBO no n.3, OTnMHaromeecfl τθμ, hto nopiiCTbiū npoMe>xyTOHHbiū cnoū coAep>KHT HeTKaHHbiū MaTepnan. 5. ycTpoūcTBO no nyHKTy 2, oTnHHatomeecn τθμ, hto β ηθμ Ha3BaHHbiū KOHTaKTHbiū aAre3MBHbiū cnoū, κροΜβ τογο, coAep>KHT reH-ycnnnTenb npoHmļaeMocTH ko>km. 6. yctpoūctbo no nyHKTy 5, OTnuMaioineecn τθμ, hto reH-ycnnnTenb npoHmļaeMocTH ko>km βκπιοηθθτ 3φκρ φopMynbι [CH3(CH2)mCOO]nR, b κοτοροϋ m «Βηηβτοη ijenbīM HiīcnoM b MHTepeane ot 8 ao 16, n paBHo 1 v\m 2, a R npeACTaenneT co6oiiHM3iiJMii anKHnbHbiū (C1-C2) ocTaTOK, to ecTb Unu He3aMeiiļeHHbiū hjim 3aMeu4eHHbiū oahoū hjih A©yMn rnAP0KcnnbHbiMM rpynnaMM. 7. ΥοτροιίστΒΟ no nyHKTy 6, OTjiMMatoineecn τθμ, mto Ha3BaHHbiM γθη-ycmiMTenb npoHMLļaeMocTM ko>km βκπιοη3ΘΤ MOHonaypaT nponmieHrnuKonn mjim MOHonaypaT προπΜ/ίΘΗΓ/ΐΜκο/ιη b οομθτθημμ c flM/iaypaTOM ΠρΟΠΜ/ΙΘΗΓ/ΙΜΚΟϋΑ. 8. ycTpoiicTBo no nyHioy 1, OTjiMHaK>meec« τθμ, hto Ha3BaHHafl nnouļaflb KOHTaKTHoro aflre3nea pacno/iaraeTcn b MHTepeajie npn6nn3MTejibHO ot 2 flo 90 cm2 m CMCTeMa npMcnoco6/ieHa aπλ noganu AeKCMeTOMMflMHa πρΜ ckopoctm npneMa b MHTepea/ie npn6riM3mejibHO ot 0,10 flo 200 MMKporpaMM b Mac. 9. yCTpoiictbo no nyHKTy 2, OTnuMaioiiļeecfl τθμ, mto αφκηιΐΗΐοιΐ1ΜΜ a,qre3MBHbM cjiom BīcnioMaeT nonMM3o6ymneH. 10. yοτροίίctbo no nymcry 1 mjim 9, oTnuMafouļeecn τθμ, mto κοητθκτηνμ aflre3MBHbiii cnoii βκπιομθθτ aKpmiaT. 11. ycTpoCicTBo no jiw6oMy M3 nymcroB 1, 5, 9 mjim 10, OTJiMMaiomeecfl ΤΘΜ, MTO ΑΘΚΟΜΘΤΟΜΜβΜΗ HaXOflMTCfl B OCHOBHOM φορΜΘ. LV 10685
Cnocotf 2 Ζ3Λ9.ΊΚ0 jyiil ΤρδΗΟΛΘβΜδΛΒΗΟΓΟ npnerja ΑθκοΜθΑθτοιηζιιβ Ρβφθρετ
OrtHCUBaeTca TpaHcaepMajīBHHfi πρκθΜ ΑθκοωθΉβτοΜΒΉκκβ, npaBOEpamaitīiiero H30Mepa MeaeToaEumHa. CnocoO BKJito?aeT ycnoKOH-Τβ,ΕΒΗΟΘ Β03ΛΘ20ΤΒ2Θ 23 ΠβΙΙΗΘΗΤβ ΠρΗΜβΗΘΗΗΘΜ βΘΚΟΜΟβθΤΟΜΪΪβΠΗδ HS ΠρΘ.Ι033ρΗΤβ JH>20 ΟΠρθΛΘΛβΚΗΟϋ ŪJIOIIia^H KOKU npH CICOpOCTH BBeseBES 2 B ΤΘΗΘΗ2Θ HpOM9KyTKa ΒρβΜΘΗΗ, ΟόθΟΠΘ^ΕΒΒΚΧφΙΧ ΚβΟόΧΟΛΗΜΗΖ ypOB9HB 0ΘΛ3Τ2ΒΗ0Γ0 Β03ίθϋθΤΒΠ«. Πρβ,ΐρίθΓθβΤΟΗ ΤΘΚΒβ TepaH9BTII-TjecKaa οζοτθμβ λπη TpaHc^epMajīBHoro npneMa JieKapcTsa. TepaneE-TE^ecKan cncieMa peajni3yeTca b φορΜθ HarjiajccH, KOTopaa npejicTaB-JIH0T C000Ž JiaM2HHpOBaHKHa Κ0ΜΠ032Τ Η3Η3Η0^0Γ0 CJI02, ΗΘΟ(5ίΐ33ΤΘΛΒ-HO - CKpeiUIiHOIHOrO am*e3HBH0r0 CJIOH, Κ0ΗΤ3ΚΤΗ0Γ0 ajCTQ32BH0r0 CJIOH Η ΟΑΗΟΓΟ HJm ΗΘΟΚΟΛόΚΗΧ ΛΟΠΟΛΗΗΤΘΛΒΗΗΣ CJI09E.

Claims (11)

  1. LV 10685 Izgudrojuma formula 1. Ierīce deksmedetomidīna transdermālai ievadīšanai caur iepriekš noteiktu veselas ādas laukumu, kas atšķiras ar to, ka tā ietver: (a) oderes slāni, kas veido izstrādājuma virsmu; (b) pret spiedienu jūtīgo lipīgo slāni, kas veido farmaceitiski pieņemamo kontakta adhēzijas slāni, kura laukums ir būtībā vienāds ar jau minēto iepriekš noteikto veselas ādas laukumu, un kas ietver materiālu, kurš ir caurlaidīgs attiecībā pret deksmedetomidīnu, pie kam minētais slānis veido ierīces galveno virsmu, kas nāk kontaktā ar ādu un tiek piestiprināta pie ādas ierīces izmantošanas laikā, pie kam ierīcē esošais deksmedetomidins pēc līdzsvara iestāšanās izplatās caur minēto adhezīvo kontakta slāni.
  2. 2. Ierīce saskaņā ar 1. punktu, kas atšķiras ar to, ka tā vēl papildus ietver: (c) saistošo adhezīvo slāni, kas izvietots starp adhezīvo kontakta slāni un oderes slāni, un saistīts ar tiem.
  3. 3. lence saskaņā ar 2. punktu, kas atšķiras ar to, ka tā vēl papildus ietver: (d) porainu starpslāni starp minēto saistošo adhezīvo slāni un minēto adhezīvo kontakta slāni, kurš ir caurlaidīgs attiecībā pret deksmedetomidīnu.
  4. 4. Ierīce saskaņā ar 3. punktu, kas atšķiras ar to, ka porainais starpslānis satur neaustu materiālu.
  5. 5. Ierīce saskaņā ar 3. punktu, kas atšķiras ar to, ka minētais kontakta adhezīvais slānis tajā vēl papildus satur nesēju - ādas caurlaidības palielinātāju.
  6. 6. Ierīce saskaņā ar 5. punktu, kas atšķiras ar to, ka nesējs - ādas caurlaidības palielinātājs ietver esteri ar formulu [CH3(CH2)mCOO]nR, kur m ir 1 vesels skaitlis intervālā no 8 līdz 16, n ir 1 vai 2, bet R ir C^-alkilgrupa, neobligāti aizvietota ar vienu vai divām hidroksilgrupām.
  7. 7. Ierīce saskaņā ar 6. punktu, kas atšķiras ar to, ka minētais nesējs -ādas caurlaidības palielinātājs ir propilēnglikola monolaurāts vai propilēnglikola monolaurāta un propilēnglikola dilaurāta maisījums.
  8. 8. Ierīce saskaņā ar 1. punktu, kas atšķiras ar to, ka minētā kontakta adhezīva laukums ir robežās aptuveni no 2 līdz 90 cm2 un ierīce ir piemērota deksmedetomidīna padevei ar uzņemšanas ātrumu aptuveni no 0,10 līdz 200 pg stundā.
  9. 9. Ierīce saskaņā ar 2. punktu, kas atšķiras ar to, ka saistošais slānis satur poliizobutilēnu.
  10. 10. Ierīce saskaņā ar 1. vai 9. punktu, kas atšķiras ar to, ka adhezīvais kontakta slānis satur akrilātu.
  11. 11. Ierīce saskaņā ar 1., 5., 9. vai 10. punktu, kas atšķiras ar to, ka deksmedetomidīns ir bāzes formā. 2
LVP-93-1079A 1989-08-18 1993-09-22 Device for transdermal administration of dexamedethomidine LV10685B (en)

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US07/395,717 US5124157A (en) 1989-08-18 1989-08-18 Method and device for administering dexmedetomidine transdermally
PCT/US1990/004575 WO1991002505A1 (en) 1989-08-18 1990-08-14 Method and device for administering dexmedetomidine transdermally

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AU6183490A (en) 1991-04-03
FI100857B (fi) 1998-03-13
HU9200517D0 (en) 1992-05-28
IE902993A1 (en) 1991-02-27
DE69019628D1 (de) 1995-06-29
PL165023B1 (pl) 1994-11-30
JP3043064B2 (ja) 2000-05-22
LT3753B (en) 1996-03-25
DK0413487T3 (da) 1995-07-17
DD297066A5 (de) 1992-01-02
ATE122899T1 (de) 1995-06-15
UA26988C2 (uk) 2000-02-28
AU639015B2 (en) 1993-07-15
BG95935A (bg) 1993-12-24
PL286525A1 (en) 1991-05-20
CA2064687A1 (en) 1991-02-19
LTIP1773A (en) 1995-07-25
EP0413487B1 (en) 1995-05-24
LV10685A (lv) 1995-06-20
WO1991002505A1 (en) 1991-03-07
NZ234749A (en) 1992-03-26
NO920521D0 (no) 1992-02-10
PT95002A (pt) 1992-02-28
IE67127B1 (en) 1996-03-06
PT95002B (pt) 1997-10-31
NO920521L (no) 1992-02-10
CN1049450A (zh) 1991-02-27
NO300408B1 (no) 1997-05-26
ZA906539B (en) 1991-06-26
DE69019628T2 (de) 1995-09-28
EP0413487A1 (en) 1991-02-20
US5124157A (en) 1992-06-23
HUT64223A (en) 1993-12-28
RU2098083C1 (ru) 1997-12-10
CA2064687C (en) 1998-04-21
JPH05503916A (ja) 1993-06-24
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CN1035922C (zh) 1997-09-24
FI920576A0 (fi) 1992-02-11

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