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Біологічно активні імплантати на основі здатних до біодеструкції поліуретанів: Автореф. дис… канд. біол. наук / Р.А. Рожнова, НАН України. Ін-т біоо

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IAOe?IIAEUeIA AEAAeAI?ss IAOE OE?A?IE

?INOEOOO A?II?AAI?*II? O?I?? OA IAOOIO?I??

OAeE 678.664:577.15:616.3:615 .462

?IAEIIAA

??oa Aiaoie??aia

A?IEIA?*II AEOEAI? ?IIEAIOAOE IA INIIA? CAeAOIEO AeI

A?IAeANO?OEOe?? IIE?O?AOAI?A

02.00.10 – a?ii?aai?/ia o?i?y

Aaoi?aoa?ao

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

Ee?a – 1999

Aeena?oaoe?th ? ?oeiien

?iaioa aeeiiaia o a?aeae?e? a?inoi?nieo iie?ia??a iaaee/iiai i?ecia/aiiy
?inoeoooo o?i??

aenieiiieaeoey?ieo niieoe IAI Oe?a?ie

Iaoeiaee ea??aiee:

aeieoi? a?ieia?/ieo iaoe, i?ioani?

Ioaeaaeca Aai?a?e Ieaenaiae?iae/

Iaoeiaee eiinoeueoaio:

aeieoi? o?i?/ieo iaoe , i?ioani?

Aeoaie A?oae?e Aiae??eiae/

?inoeooo i?iaeai iaoa??aeiciaanoaa IAI Oe?a?ie

caa?aeoaa/ o?i?ei-aiae?oe/iiai a?aeae?eo

Io?oe?ei? iiiiaioe:

aeieoi? o?i?/ieo iaoe, i?ioani?

A?aeia Aiaoie?e Iao?iae/

?inoeooo o?i?? aenieiiieaeoey?ieo niieoe IAI Oe?a?ie

caa?aeoaa/ a?aeae?eo neioaco e?i?eieo iie?ia??a

aeieoi? a?ieia?/ieo iaoe, i?ioani?

?aaeaanueeee TH??e Eaii?aeiae/

?inoeooo a?ii?aai?/ii? o?i?? oa iaooio?i?? IAI Oe?a?ie

caa?aeoaa/ a?aeae?eo no?oeoo?e oa ooieoe?? a?eea

I?ia?aeia onoaiiaa:

?inoeooo a?io?i?? ?i. I.A. Iaeeaae?ia IAI Oe?a?ie, i. Ee?a

Caoeno a?aeaoaeaoueny “2” ea?oiy 1999 ?. i 10 00 aiaeei? ia can?aeaii?
niaoe?ae?ciaaii? a/aii? ?aaee

Ae 26.220.01 a ?inoeooo? a?ii?aai?/ii? o?i?? oa iaooio?i?? IAI Oe?a?ie,
253660, Ee?a-94, aoe. Io?iainueea, 1

C aeena?oaoe??th iiaeia iciaeiieoenue a a?ae?ioaoe? ?inoeoooo
a?ii?aai?/ii? o?i?? oa iaooio?i?? IAI Oe?a?ie,

253660, Ee?a-94, aoe. Io?iainueea, 1

Aaoi?aoa?ao ?ic?neaiee ” 1 ” aa?aciy 1999 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? a/aii? ?aaee
Ae.I. Oaaei?ye

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue oaie. Iaiao?aei?noue noai?aiiy a?ieia?/ii aeoeaieo
?iieaioao?a aeey ieanoeee e?noeiai? oeaieie iaoiiaeaia cia/iei
?iciianthaeaeaiiyi aeaaaia?a-oeaii-aeeno?io?/ieo caoai?thaaiue o?aaoa oa
aaeeeeo noaeia?a, ye? iio?aaothoue o??o?a?/iiai e?eoaaiiy, a oaeiae
ca?eueoaiiyi e?eueeino? oai?eo c e?noeiaeie aeaoaeoaie i?ney o?aaie,
iooeei, e?no oa ?ioeo caoai?thaaiue iii?ii-?ooiaiai aia?aoo.

Aeei?enoaiiy eiino?oeoe?e aiaeii?ioac?a c iaoae?a, aei- oa
enaiio?ainieaioao?a, neioaoe/ieo oeaiei ye e?noeiaiai ieiiaoaaeueiiai
iaoa??aeo iaiiaeeeaa a ca’yceo c ?o a?aeiiniith a?inoi?ni?noth oa
aenieith aonoeiith.

No/ania o?i?y iie?ia??a iaaea? a?ieia?? oa iaaeeoeei? iaiaiaaeaiee
ani?oeiaio aeo?aeieo iie?ia??a, ye? iiaeooue aooe iniiaith aeey
aeaioiaeaiiy a?ieia?/ii aeoeaieo eiiiiceoe?eieo e?noeiaeo ?iieaioao?a.

Aaeueie aeooaeueii aeei?enoiaoaaoe a yeino? iin?y a?ieia?/ii aeoeaieo
?a/iaei ii?eno? iie?o?aoaie, ye? iathoue caeaoi?noue aei
a?iaeano?oeoe??, a oaeiae iie?ia?ecothoueny a aeaoaeoi?e ii?iaeiei?
i?eeiath/e ?? oi?io oa ooai?thth/e aaeaac?eiee ca’ycie ia iaae?
?iciiae?eo iie?ia? – e?noea.

Ne?ae a?aecia/eoe, ui eeoa aeaye? aeaiaioe a neeaae? iie?o?aoaiiaiai
?iieaioaoo iiaeooue neoaeeoe oeaio?aie ?aaaia?aoe?? oa iaoiiaethaaoe
iiaeaeueoa ?ioaineaia cai?uaiiy cacia/aiiai aiaeii?ioaco ?aaaia?iaaiith
e?noeith. Aei oaeeo a?ieia?/ii aeoeaieo ?a/iaei iaeaaeeoue
a?ae?ieneaiaoeo (AAI), yeee a?aeiineoueny aei eaeueoe?e-oinoaoii?
a?iea?ai?ee.

A oeueiio iai?yieo ni?eueieie coneeeyie iaaeee?a oa o?i?e?a-neioaoee?a
aeinyaioo? /eiae? oni?oe, aea caeeoa?oueny aeineoue aaaaoi iaae??oaieo
i?iaeai, o oiio /ene? ieoaiiy uiaei iiaeeeaino? noeioethaaiiy i?ioeano
?aaaia?aoe?? e?noeiai? oeaieie ca ?aooiie iaaeaiiy iie?ia?iiio
?iieaioaoo niaoeeo?/ii? a?ieia?/ii? aeoeaiino?.

Oi/a a na?oia?e i?aeoeoe? (J.J. Quist, 1995, W. Bonfield, 1998)
?ioaineaii i?iaiaeyoueny ?iaioe ii noai?aiith eiiiiceoe?eieo iie?ia?ieo
iaoa??ae?a aeey aiaeii?ioacoaaiiy, ye? i?noyoue a nai?io neeaae?
a?iea?ai?eo, aea a?ieia?/ii aeoeaieo iie?ia?ieo ?iieaioao?a ia iniia?
caeaoieo aei a?iaeano?oeoe?? iie?o?aoai?a, ye? iiaee a noeioethaaoe
i?ioean inoaineioaco c iaeii/aniei cai?uaiiyi e?noeiaei ?aaaia?aoii, ia
nueiaiaei? ua iaaeinoaoiuei.

Aea/aiiy caeiiii??iinoae i?ioean?a aca?iiae?? iie?o?aoaiiaeo
?iieaioao?a, iaiiaiaieo a?ieia?/ii aeoeaieie niieoeaie, c oeaieiiei
na?aaeiaeuai i?aai?cio ia?aaeaa/a? aeaoaeueia aea/aiiy ?o
o?ceei-o?i?/ieo aeanoeainoae in vivo oa in vitro.

Iiaeeea?noue iaaeaiiy aiaeii?ioaco e?eoaaeueieo aeanoeainoae
i?ieiiaiaaii? ae??, ni?yiiaaieo ia noeioethaaiiy ooieoe?e ee?oeiiiai
eaioethaa ?ioiii? nenoaie, ? oaeiae iaeiei c iniiaieo iai?yie?a o
i?iaeai? noai?aiiy a?ieia?/ii aeoeaieo ?iieaioao?a aeey i?oiiaae??.
Iniaeeai oea aaaeeeai i?e ieanoeoe? e?noeiaeo aeaoaeo?a, ooai?aieo
aiane?aeie iaoieia?/ieo i?ioean?a (inoaii??e?o, aanoean A?iae?, iooeeie
oa ?io?.).

Ae??oaiiy on?o oeeo ieoaiue aaaeeeaa ye a oai?aoe/iiio, oae ? a
i?aeoe/iiio aniaeoao. Oea, ianaiia?aae, oe?eani?yiiaaiee iiooe
a?ieia?/ii aeoeaieo niieoe, ye? iathoue inoaio?iiio, i?oiaaiio (H.S.
Cheunig, 1984) ae?th, oa e?ea?nueeeo ?a/iaei, ? noai?aiiy i?eioeeiiai
iiaeo ?iieaioao?a aeey aiaeii?ioacoaaiiy, caeaoieo ?ioaineaii
noeioethaaoe ?aaaia?aoe?th e?noeiai? oeaieie c iaeii/aniith
i?ieiiaiaaiith oa?iaeieia?/iith ae??th a i?noe? canoinoaaiiy.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie. Aeena?oaoe?eia
?iaioa aeeiioaaeanue a ?aieao oaiaoe/ieo ieai?a ?OAN IAI Oe?a?ie ca?aeii
c i?ia?aiith “Noai?aiiy iie?ia?ieo caeaoieo aei a?iaeano?oeoe??
?iieaioao?a, ye? ni?eythoue i?ioeanai ?aaaia?aoe?? a i?noe?
canoinoaaiiy, oa iie?ia??a, no?eeeo a na?aaeiaeuao i?aai?cio” (1993-1997
?.?.), iiia? aea?ae?a?no?aoe?? 0198U001263.

Iaoa ? caaea/? aeine?aeaeaiiy. Iaoa ?iaioe – ia iniia? i?iaaaeaieo
o?ceei-o?i?/ieo oa a?ieia?/ieo aeine?aeaeaiue aenia?eiaioaeueii
iaa?oiooaaoe iiaeeea?noue noai?aiiy iiaeo a?ieia?/ii aeoeaieo
iie?o?aoaiiaeo ?iieaioao?a aeey aiaeii?ioacoaaiiy, caeaoieo ?ioaineaii
noeioethaaoe i?ioeane e?noeiooai?aiiy caaaeyee aaaaeaiith aei ?o neeaaeo
a?ae?ieneaiaoeoo, yeee neoaeeoue iniiaith i?ioean?a inoaineioaco a
?aaaia?oth/?e oeaiei?.

Caaea/? aeine?aeaeaiiy:

1. Noai?aiiy a?ieia?/ii aeoeaieo ?iieaioao?a aeey ieanoeee e?noeiai?
oeaieie, caeaoieo ?ioaineaii noeioethaaoe i?ioean inoaineioaco.

2. Aea/aiiy aieeao iai?aai?/ii? neeaaeiai? iie?o?aoaiiaeo eiiiiceoe?e ia
?o o?ceei-o?i?/i? aeanoeaino? a oiiaao in vivo c aeei?enoaiiyi
o?ceei-o?i?/ieo oa a?ieia?/ieo iaoiae?a aiae?co.

3. Aeine?aeaeaiiy iiaeeeaino? iaaeaiiy i?ieiiaiaaii? e?eoaaeueii? ae??
iie?o?aoaiiaei eiiiiceoe?yi c a?ae?ieneaiaoeoii.

4. Aeine?aeaeaiiy no?oeoo?ii-ii?oieia?/ieo ci?i iie?o?aoaiiaeo
eiiiiceoe?e c a?ae?ieneaiaoeoii oa ?ioiiiiaeoeyoi?ii – eaaai?cieii (EAA)
i?ae aieeaii na?aaeiaeua i?aai?cio.

5. Aea/aiiy iiaeeeaino? aeoeaaoe?? inoaiaaiaco i?e canoinoaaii?
?ic?iaeaieo a?ieia?/ii aeoeaieo iie?o?aoaiiaeo eiiiiceoe?e.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. ?acoeueoaoii i?iaaaeaii?
?iaioe ? iaoeiaa iaa?oiooaaiiy aeioe?eueiino? noai?aiiy iie?o?aoaiiaeo
?iieaioao?a c a?iea?ai?eith oa aea/aiiy o?ceei-o?i?/ieo oa?aeoa?enoee
oeeo iaoa??ae?a i?e ?iieaioaoe?? a i?aai?ci.

Aaoi?ii aia?oa aeei?enoaii a?ieia?/ii aeoeaio ea?ai?eo (a?ae?ieneaiaoeo)
a neeaae? iie?o?aoaiiai? iniiae c iaoith iaaeaiiy ?e caeaoiino?
?ioaineaii noeioethaaoe i?ioean inoaooai?aiiy.

Aaoi?ii aia?oa iieacaii:

– aaaaeaiiy a?ae?ieneaiaoeoo oa eaaai?cieo a ??cieo ni?aa?aeiioaiiyo a
iie?o?aoaiiao iao?eoeth cia/ii i?aeaeuo? ?? caeaoi?noue aei aaeaac??;

– i?enooi?noue a?ae?ieneaiaoeoo a caeaoi?e aei a?iaeano?oeoe??
eiiiiceoe?? noeioeth? i?ioean iaeiie/aiiy iai?aai?/ii? neeaaeiai?
e?noeiai? oeaieie ii an?e ?? ian?;

– i?enooi?noue a?ae?ieneaiaoeoo a eiiiiceoe?? c eaaai?cieii ia ciaioo?
i?ioeaio aeoiaeo e?e?a a oiiaao in vitro ?, oaeei /eiii, ia ciaioo? eiai
oa?iaeieia?/io ae?th in vivo.

I?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a iieyaa? a noai?aii? iiaeo
a?ieia?/ii aeoeaieo iie?ia?ieo ?iieaioao?a, caeaoieo ?ioaineaii
noeioethaaoe i?ioeane ?aaaia?aoe?? e?noeiai? oeaieie caaaeyee
i?enooiino? a eiiiiceoe?? a?iea?ai?ee (a?ae?ieneaiaoeoo), yea ? oeaio?ii
inoaineioaco.

Iiaeaeueoa ai?iaaaeaeaiiy a iaaee/io i?aeoeeo aeuacacia/aieo ?iieaioao?a
a?aee?eaa? iia? iiaeeeaino? a oaeineiiaeaii? oaoi?ee o??o?a?/iiai
ao?o/aiiy, ui ianaiia?aae i?eaaaea aei ciaioaiiy /ano iia?aoe?e oa
i?neyiia?aoe?eieo oneeaaeiaiue.

Iie?o?aoaiia? eiiiiceoe?? c a?ae?ieneaiaoeoii i?ieoee oieneeieia?/i?
aei?iaoaaiiy ? iiaeooue aooe ?aeiiaiaeiaai? aeey ee?i?/ieo aei?iaoaaiue.

Iniaenoee aianie aeena?oaioa iieyaa? a noai?aii? a?ieia?/ii aeoeaieo
iie?ia?ieo ?iieaioao?a aeey ieanoeee e?noeiai? oeaieie, a oaeiae o
aeeiiaii? eaai?aoi?ieo aeine?aeaeaiue oa aenia?eiaio?a ia oaa?eiao.
Aaoi?o iaeaaeaoue ocaaaeueiaiiy, aiae?c io?eiaieo ?acoeueoao?a oa
aenoiaiiy a?iioac, ye? iiyniththoue iaoai?cie aea/aieo i?ioean?a.

Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??. Iaoa??aee aeena?oaoe?eii? ?iaioe
aoee i?aaenoaaeai? ia VIII Oe?a?inuee?e eiioa?aioe?? c
aenieiiieaeoey?ieo niieoe (Ee?a, 1996), 8 Iaoe?iiaeuei?e oeie?-nai?ia??
c i?aeia?iaeiith o/anoth “Niaeo?ineii?y iieaeoe ? e?enoae?a” (Noie,
1997), 3rd Seminar and Meeting on Ceramics, Cells and Tissues
“Bioceramic coatings for Guided bone growth” (Italy, Faenza, 1996);
International Surgery Congress: Wounds, Burns, Dressing (Tel-Aviv,
Israel, 1998). Iaoa??aee aeena?oaoe?? aeiiia?aeaeenue ia iaoeia?e nan??
A?aeae?eaiiy o?i?? IAI Oe?a?ie, i?enay/ai?e 80-??//th IAI Oe?a?ie
(Oa?e?a, 1998). ?acoeueoaoe ?iaioe aeiiia?aeaeenue ? iaaiai?thaaeenue ia
can?aeaiiyo a/aii? ?aaee oa iaoeiaeo nai?ia?ao a ?inoeooo? o?i??
aenieiiieaeoey?ieo niieoe IAI Oe?a?ie.

Ioae?eaoe??. Iaoa??aee aeena?oaoe?eii? ?iaioe aeeeaaeai? o 10
ioae?eaoe?yo, c ieo 6 noaoae a iaoeiaeo aeo?iaeao ? a iaoa??aeao
iaoeiai? nan?? oa 4 oace eiioa?aioe?e. No?oeoo?a oa ianya ?iaioe.
Aeena?oaoe?eia ?iaioa aeeeaaeaia ia 146 noi??ieao iaoeiiieniiai oaenoo ?
neeaaea?oueny c? anooio, 3 ?icae?e?a: iaeyaeo e?oa?aoo?e, iieno
iaoa??ae?a ? iaoiae?a, ?acoeueoao?a oa iaaiai?aiue, cae?i/aiiy,
aeniiae?a, oa nieneo aeei?enoaieo e?oa?aoo?ieo aeaea?ae, ui i?noeoue 163
iineeaiue ia ?iaioe a?o/eciyieo oa ca?oa?aeieo a/aieo. Iaoa??aee
aeena?oaoe?eii? ?iaioe ?ethno?iaai? 23 ?enoieaie oa 10 oaaeeoeyie.

Iaoiaeieia?y oa iaoiaee aeine?aeaeaiiy. Ia’?eoaie aeine?aeaeaiiy aoee
iie?o?aoaiia? eiiiiceoe?? c a?ieia?/ii aeoeaieie niieoeaie –
a?ae?ieneaiaoeoii oa eaaai?cieii. A?noioiene/i?noue ?ic?iaeaieo
eiiiiceoe?e aecia/aee iaoiaeii eoeueoo?e oeaiei (Aaeaoaiei I.A., 1979).
Ii noaiaea?oi?e iaoiaeeoe? aecia/aee i?oei?noue ia cnoa iie?ia?ieo
eiiiiceoe?e c ??ciei ai?noii a?ae?ieneaiaoeoo. Aieea a?ieia?/ii aeoeaieo
iaiiaithaa/?a ia o?ceei-o?i?/i? aeanoeaino? iie?o?aoaiiaeo eiiiiceoe?e a
oiiaao in vivo aea/aee ca aeiiiiiaith iaoiaeo ??aiiaaaeiiai iaa?yeaiiy
O. ?aia?a (Flory R., 1953), iaoiaeii aaaaoie?aoiiai ii?ooaiiiai iiaiiai
aioo??oiueiai a?aeaeaaiiy (AIIAA) niaeo?ineii??, ?aioaaii-no?oeoo?iei
aiae?cii. I?e ?iieaioaoe?? caoaa?ae?eeo eiiiiceoe?e a i?aai?ci
aenia?eiaioaeueieo oaa?ei aeoeai?noue eeneeo oa eoaeieo oinoaoac a
niieo/iioeaieiieo eainoeao aecia/aee iaoiaeii Aannay-Eio??-A?aea
(Eiia?ia O.?., 1976). Ai?no a?eea aecia/aee ca A?aaeoi?aeii (Bradford
M.M., 1976). I?iaiaeeee a?noieia?/i? aeine?aeaeaiiy niieo/iioeaieiieo
eainoe i?e noaeooaeuei?e ?iieaioaoe?? iie?o?aoaiiaeo eiiiiceoe?e c
a?ae?ieneaiaoeoii oa i?e ieanoeoe? e?noeiaeo aeaoaeo?a
aenia?eiaioaeueieo oaa?ei, caaa?aeaiiy oeaiei ii Aiii??. Aeo?ae e?e?a
(eaaai?cieo) c iie?o?aoaiiaeo eiiiiceoe?e aecia/aee ca aeiiiiiaith
aeno?aoe?eii-oioiiao?e/iiai iaoiaeo (Ei?aiiai E.I., 1977, Ia/a?aa E.TH.,
Aaeaoaiei I.A. 1989). No?oeoo?ii-ii?oieia?/i? ci?ie a ?iieaioaoao c
a?ae?ieneaiaoeoii oa eaaai?cieii aeine?aeaeoaaee ?aioaaii-no?oeoo?iei
iaoiaeii aiae?co. Iaea?aeai? aenia?eiaioaeuei? aeai? ii?aoeueiaai?
noaoenoe/ii (Iiioeaae/ooa-A??iaaia A.A., 1964; Iea?i E.A., 1960).

INIIAI? ?ACOEUeOAOE AeINE?AeAEAIIss

Ii??aiyeueia ioe?iea caeaoiino? aei aaeaac?? eiiiiceoe?eiiai iaoa??aeo
aeey ieanoeee e?noeiaeo aeaoaeo?a

C iaoith noai?aiiy eiiiiceoe?eiiai iaoa??aeo aeey ieanoeee e?noeiaeo
aeaoaeo?a aeei?enoai? aeo?aei? eiiiiiaioe :

1. Iie?ia?ia iniiaa – ie?aiao??o?aoaiae??cioe?aiao ia iniia?
iie?ienei?ii?eaiae?eieth (iie?ao?? ia?ee Eai?ie 1502) oa
oieo?eaiae??cioe?aiaoo (O65/35);

2. I?enei?thaa/ iie?ia?ecaoe?? – 2,4,6-o?en(aeeiaoeeai?iiiaoee)oaiie;

3. A?iea?ai?ea – a?ae?ieneaiaoeo;

4. E?ea?nueea ?a/iaeia – eaaai?cie.

Ia iniia? aeacaieo eiiiiiaio?a io?eiai? eiiiiceoe?? (IO-20AAI,
IO-30AAI, IO-20AAI-6EAA, IO-30AAI-6EAA), aea ai?no a?ae?ieneaiaoeoo
neeaaeaa 20 % oa 30 % aei iane iie?ia?ii? iniiae. E?euee?noue
eaaai?cieo, a?aoiaoth/e eiai oa?iaeieia?/io ae?th, neeaea 6 % aei iane
iie?o?aoaio.

Iie?ia?ia iniiaa ? noi?ooth iae?iae??cioe?aiao?a caaaeueii? oi?ioee:

OCN – R – NH – C-O – NI2 – NI – In – C – NH – R – NCO, (1)

||
||

O
CH3 O

aea R – caeeoie oieo?eaiae??cioe?aiaoo (OAe?) O 65/35; caaaeueia noia
?ciia??a 2,4-, 2,6- ia iaioa 99,6 %;

n – nooi?iue iie?ia?ecaoe?? iie?ienei?ii?eaiae?eieth (n = 15-35).

?aaeoe?y iie?i?e?aeiaiiy eiiiiceoe?? a?aeaoaa?oueny i?ae aieeaii aieiae
aeeaeo oeaiei (o aeiaaeeo oaa?ae?iiy a na?aaeiaeu? i?aai?cio) ?
i?ecaiaeeoue aei ooai?aiiy ea?aai?aeieo ca’yce?a. Caoaa?ae?eee
iie?o?aoaiiaee iin?e yaey? niaith n?o/anoee iie?ia? i?e?iii?enoi?
no?oeoo?e c aeioaiaoieie oa a?o?aoiaeie aoceaie ?icaaeoaeaiiy, eio??
a?ae?ie?cothoueny a i?ioean? a?iaeano?oeoe?? iie?o?aoaio.

Caaaeueia no?oeoo?a caoaa?ae?ei? iie?ia?ii? iniiae:

o?aoai

O O
O
(2)

|| || ||

– R- N – C – O – R1 – O – C – NH – R – NH – C – O – R1 –

|

CO- NH – R – NH – C – O – R1- O – C – NH – R – NH – C = O

|| ||
|

aeioaiao O O
N __________ R –

|

O=C

|

NH__________R-

a?o?ao

R – caeeoie oieo?eaiae??cioe?aiaoo, (OAe?) O 65/35;

R1 – caeeoie iie?ienei?ii?eaiae?eieth, II = 1500.

1. Aeioaiaoi? aocee ?icaaeoaeaiue.

-R–NCOO–R1-+ HOH -R–NHCOO–R1- + -R–NHCOOH
(3)

CONH–R –

-R–NH–COOH -R-NH2 + CO2
(4)

2. A?o?aoia? aocee ?icaaeoaeaiue.

-R–NCONH–R- + HOH -R–NHCONH–R- + -R-NHCOOH
(5)

CONH–R-

-R–NH–COOH -R–NH2 + CO2
(6)

Iaei??th c iaeaaaeeea?oeo oa?aeoa?enoee iaiiaiaieo iie?o?aoaiiaeo
eiiiiceoe?e, ye? iiaeooue aeei?enoiaoaaoenue aeey ieanoeee e?noeiai?
oeaieie, ? ?o caeaoi?noue ooai?thaaoe i?oeiee aaeaac?eiee ca’ycie ia
iiaa?oi? ?iciiae?eo aeaio na?aaeiaeu e?noea-iie?ia?ia eiiiiceoe?y.

C iaoith aeai?o iaea?eueo iioeiaeueiiai neeaaeo iie?ia?ii? eiiiiceoe?? c
a?iea?ai?eith aeey ieanoeee e?noeiai? oeaieie i?iaiaeeee ii??aiyeueia
aea/aiiy o?ceei-o?i?/ieo ia?aiao??a ?yaeo io?eiaieo eiiiiceoe?e ia
iniia? iie?o?aoaio c ??ciei ai?noii a?ae?ieneaiaoeoo.

Aeine?aeaeaiiy iie?ia?ieo eiiiiceoe?e ia i?oei?noue, yea iaoiiaeaia ?
aaeaac?eieie aeanoeainoyie, iieacaee (oaae.1), ui noi?nia aaaaeaiiy aei
neeaaeo iie?o?aoaiiaiai iin?y a?ae?ieneaiaoeoo oa eaaai?cieo cia/ii
i?aeaeuo? ?? cia/aiiy.

Oaaeeoey 1 – Aaeaac?ei? aeanoeaino? iie?ia?ieo eiiiiceoe?e, ye? i?noyoue
a nai?io neeaae? a?ae?ieneaiaoeo oa eaaai?cie

I?oei?noue ia cnoa, o 10,
IIaIOIO-20AAIIO-30AAIIO-20AAI-6EAAIO-30AAI-6EAA0,5+0,1

0,44+0,0570,38+0,1521,14+0,11,11+0,016

A iiaeaeueoiio aeine?aeaeoaaeenue eiiiiceoe?? c 20 % ai?noii
a?ae?ieneaiaoeoo (IO-20AAI, IO-20AAI-6EAA), ai iaiiaiaiiy iie?o?aoaio 30
% a?ae?ieneaiaoeoo ca?eueoo? /an i?eaiooaaiiy oa oaa?ae?iiy eiiiiceoe?e,
ui iaaaaeaii i?e ?o aeei?enoaii? ca i?ecia/aiiyi.

Aea/aiiy aieeao iai?aai?/ii? neeaaeiai? iie?o?aoaiiaeo eiiiiceoe?e ia ?o
o?ceei-o?i?/i? aeanoeaino? in vivo

I?iaeaia noai?aiiy ?iieaioao?a aeey ieanoeee e?noeiai? oeaieie ia iniia?
iie?o?aoaiiaeo iin??a, iaiiaiaieo a?iea?ai?eith, iio?aao? ?aoaeueiiai
aea/aiiy aieeao iai?aai?/ii? neeaaeiai? eiiiiceoe?e ia ?o o?ceei-o?i?/i?
aeanoeaino? a oiiaao aioo??oiueiai na?aaeiaeua i?aai?cio.

C oe??th iaoith caoaa?ae?e? iie?o?aoaiia? eiiiiceoe?? IO-20AAI,
IO-20AAI-EAA, a oaeiae eiio?ieuei? c?acee IO, IO-6EAA o aeaeyae?
ae??aiiii?enoeo aoaie aoee noaeooaeueii ?iieaioiaai? aenia?eiaioaeueiei
oaa?eiai ia ??ci? oa?i?ie.

O?ceei-o?i?/i? ci?ie o aeuacacia/aieo eiiiiceoe?yo a oiiaao in vivo
aeine?aeaeoaaee ca aeiiiiiaith iaoiae?a ??aiiaaaeiiai iaa?yeaiiy
Oei??-?aia?a, AIIAA niaeo?ineii??, ?aioaaii-no?oeoo?iei aiae?cii.

?acoeueoaoe aeine?aeaeaiiy o?ceei-o?i?/ieo aeanoeainoae (oaae.2)
iieacaee, ui aeey eiio?ieueieo c?ace?a IO, IO-6EAA aei 6 i?nyoe?a
?iieaioaoe?? ia? i?noea i?aeaeuaiiy cia/aiue ??aiiaaaeiiai nooiaith
iaa?yeaiiy oa ciaioaiiy cia/aiue aonoeie. Iaaiaee, iie?ia?i? eiiiiceoe??
c a?ae?ieneaiaoeoii (IO-20AAI, IO-20AAI-6EAA) aei 6 i?nyoe?a
?iieaioaoe?? ciaioothoue cia/aiiy ??aiiaaaeiiai nooiaith iaa?yeaiiy oa
ca?eueoothoue naith aonoeio.

Oaaeeoey 2 – Ci?ia aeeooc?eieo ia?aiao??a oa aoaeoeaii? aonoeie coeaee a
oiiaao in vivo aeey iie?o?aoaiiaeo eiiiiceoe?e, ye? i?noyoue AAI

Ia??iae, i?nyoeueNeeaae eiiiiceoe?e??aiiaaaeia

nooi?iue

iaa?yeaiiy

Ia’?iia aeiey iie?ia?o a iaa?ye-io

c?aceoAonoeia iie?ia?.

c?acea,

ea/i3Aoaeoeaia aonoeia coeaee,

iieue-1

eiio?ieueIO1,86450,34910,70440,03995
IO-6EAA1,80660,35630,79190,05323IO-20AAI5,69550,14820,84290,01030IO-20AA
I-6EAA3,73970,21150,89510,012001IO
2,17950,30280,67740,03289IO-6EAA2,08450,32420,83300,02458IO-20AAI2,38720
,29590,76600,02080IO-20AAI-6EAA1,82760,35820,65300,020423IO3,14110,24190
,68540,02550IO-6EAA2,91540,25540,79340,01072IO-20AAI2,29370,30510,79320,
02900IO-20AAI-6EAA2,55480,28500,85990,021006IO3,81100,26240,78530,01170I
O-6EAA4,29100,18900,76540,01060IO-20AAI2,85090,25970,76990,04200IO-20AAI
-6EAA2,20510,31200,85000,02600

Oaeei /eiii, aeey eiio?ieueieo c?ace?a IO oa IO-6EAA ?c ca?eueoaiiyi
/ano ?iieaioaoe?? niinoa??aa?oueny ciaioaiiy cia/aiue aoaeoeaii? aonoeie
coeaee, ui ? na?ae/aiiyi i?ioeano ?o a?iaeano?oeoe??. A oie aea /an,
aeey c?ace?a eiiiiceoe?e IO-20AAI, IO-20AAI-6EAA niinoa??aa?oueny
ca?eueoaiiy cia/aiue aoaeoeaii? aonoeie coeaee, i?e/iio, aeey
eiiiiceoe?? IO-20AAI-6EAA oe? cia/aiiy iaio?, ui iiaea aooe iiyniaii
i?enooi?noth eaaai?cieo, yeee, ye a?aeiii, iineeth? ee?oeiiee oeyo
a?iaeano?oeoe?? iie?ia?ii? iniiae c iaeii/aniei i?enei?aiiyi i?ioean?a
?aaaia?aoe??.

Io?eiai? ?acoeueoaoe iiyniththoue aeai? AIIAA niaeo?ineii?? oa
?aioaaii-no?oeoo?iiai aiae?co.

Ia niaeo?ao iie?o?aoaio i?ae aieeaii na?aaeiaeua aeeaiai i?aai?cio ia?
i?noea cieaeaiiy a?aeiinii? ?ioaineaiino? nioa iiaeeiaiiy a iaeanoyo
1720 ni-1 (Ai?aeI,N=I), 1230 ni-1 (N-I, C-N ), 1100 ni-1 (N-I, N-N).
Ciaioaiiy ?ioaineaiino? aeacaieo nioa iiaeeiaiiy c /anii ia?aaoaaiiy
c?ace?a iie?o?aoaio a oiiaao in vivo iia’ycaia c a?ae?ie?cii neeaaeiiai
oa i?inoiai ao??iiai ca’yceo iie?ia?ii? iniiae, ui ? aeieacii i?ioeano
?? a?iaeano?oeoe??.

I?e ii??aiyii? ?*-niaeo??a iie?o?aoaio, a?ae?ieneaiaoeoo oa eiiiiceoe?e
IO-20AAI, IO-20AAI-6EAA aoei anoaiiaeaii, ui i?enooi?noue AAI a iie?ia??
/?oei aeyaeeanue iayai?noth nioa iiaeeiaiiy 575, 610, 635 ni-1
a?ae?ieneaiaoeoo.

*a?ac o?e i?nyoe? ia?aaoaaiiy a i?aai?ci? ia ?*-niaeo?ao c?ace?a
eiiiiceoe?e c AAI niinoa??aathoueny ci?ie, ye? a?eueo /?oei i?iyaeai?
i?ney 6 i?nyoe?a ?iieaioaoe?? oa ae?aaeai? a cia/iiio ca?eueoaii?
?ioaineaiino? nioa iiaeeiaiiy a?ae?ieneaiaoeoo 575, 610, 635 ni-1.

?*-niaeo?e, ciyo? c iiaa?oi? oa aioo??oiuei? /anoeie aeine?aeaeoaaieo
c?ace?a, na?ae/aoue i?i c?inoaiiy a ieo e?eueeino? AAI c /anii
ia?aaoaaiiy a na?aaeiaeu? i?aai?cio, i?e/iio ia o?eueee ia iiaa?oi?, a e
ii an?e ian?.

Io?eiai? aeai? (oaae. 3) aeicaieythoue aeaoe e?euee?nio ioe?ieo
aeyaeaiiai aoaeoo ca?eueoaiiy e?eueeino? a?ae?ieneaiaoeoo a eiiiiceoe?yo
IO-20AAI, IO-20AAI-6EAA, ye? ia?aaoaaee o?eaaeee /an a i?aai?ci?
aenia?eiaioaeueieo oaa?ei.

Oaaeeoea 3 – Aeaii? AIIAA niaeo?ineii?? aeey iie?ia?ieo eiiiiceoe?e c
a?ae?ieneaiaoeoii aei oa i?ney ?iieaioaoe??

?C?acieA?aeiioaiiy iioe/ii? aonoeie nioa iiaeeiaiiy 575

830575

1230575

1380610

830610

1230610

1380ni-1

N?.1.IO-20AAI eiio?.1,320,500,561,100,420,46_2.IO-20AAI, 6 i?n. ?iie.,
aa?o. oa?4,101,101,422,90,971,00_3.IO-20AAI ,6 i?n.

?iie., aioo?. oa?2,700,960,962,220,790,79_4.IO-20AAI-6EAA

eiio?ieue1,30,50,561,10,410,46_5.IO-20AAI-6EAA

6 i?n. ?iieaioaoe??2,601,101,302,200,951,15_6.IO-20AAI

?2/?13,12,82,52,62,32,22,67.IO-20AAI

?2/?31,51,41,51,31,21,21,358.IO-20AAI-6EAA

?5/?42,02,22,32,02,32,52,2

Oae, ca 6 i?nyoe?a ?iieaioaoe?? a c?aceo IO-20AAI e?euee?noue AAI
ca?eueoeeanue a 2,6 ?ace. I?e oeueiio, a na?aaei?e /anoei? ii oiauei?
c?aceo eiai e?euee?noue ae?inea a 1,35 ?ace. A eiiiiceoe?? IO-20AAI-6EAA
e?euee?noue AAI ca?eueoeeanue a 2,2 ?ace.

Oaeei /eiii, ca?aeii c iaea?aeaieie ?acoeueoaoaie o?ceei-o?i?/ieo
aeine?aeaeaiue iie?ia?i? eiiiiceoe?? IO-20AAI, IO-20AAI-6EAA
ca?eueoothoue aonoeio coeaee o a?aeiioaii? aei eiio?ieth (IO, IO-6EAA),
a aeai? AIIAA niaeo?ineii?? aeacothoue ia cia/ia iaeiie/aiiy
iai?aai?/ii? neeaaeiai? e?noeiai? oeaieie eiiiiceoe?yie a i?aai?ci?, aei
oiai ae ia ia iiaa?oi?, a ii an?e ian?, ui iiaea a?aeaoaaoeny aiane?aeie
inaaeaeaiiy aiaoeoiai? oace c oeaieiii? ??aeeie a ?acoeueoao? i?ioeano
?ic/eio – ia?ainaaeaeaiiy a?ae?ieneaiaoeoo.

C iaoith aea/aiiy i?ioeano iaeiie/aiiy iai?aai?/ii? neeaaeiai?
e?noeiai? oeaieie iie?o?aoaiiaeie eiiiiceoe?yie IO-20AAI, IO-20AAI-6EAA
in vivo aeine?aeaeoaaee ci?ie a ?o iaaeiieaeoey?i?e oa
oaciai-e?enoae?/i?e no?oeoo?ao i?e ??cieo no?ieao ?iieaioaoe??
aenia?eiaioaeueiei oaa?eiai.

Aiae?c e?eaeo iaeieooiaiai ?icn?yiiy IO iieacaa, ui i?ae aieeaii
na?aaeiaeua aeeaiai i?aai?cio ia i?ioyc? 3-o oa 6-oe i?nyoe?a
?iieaioaoe?? ca?eueoo?oueny aeaoaeoi?noue i?inoi?iai? iae?i?ao?oee
aei?noeeo aeiiai?a iie?o?aoaiiai? iao?eoe?.

Aeey eiiiiceoe?? IO-20AAI iii?oia iine?aeiaia iaeiie/aiiy iai?aai?/ii?
neeaaeiai? e?noeiai? oeaieie c? ca?eueoaiiyi /ano ia?aaoaaiiy in vivo. A
eiio?ieueiiio c?aceo aeiiaiia no?oeoo?a aei?noeeo aeie?a iie?o?aoaiiai?
iao?eoe? neaai ae?aaeaia. Ia e?ea?e ?icn?yiiy eiiiiceoe?? IO-20AAI, yea
ciaoiaeeeanue 3 i?nyoe? a na?aaeiaeu? i?aai?cio, ?aae?co?oueny eeoa
ne?ae ?ioa?oa?aioe?eiiai iaeneioio (2 = 130′), yeee aeaiiino?o?
i?aeoe/ii iiaia ?oeioaaiiy iae?i?ao?oee aei?noeeo aeiiai?a
iie?o?aoaiiai? iao?eoe?. Oanoei?ny/ia ia?aaoaaiiy a i?aai?ci?
i?ecaiaeeoue aei iiaiiai ?? ?oeioaaiiy, ui aeeeeeaii ca?eueoaiiyi
e?eueeino? AAI a eiiiiceoe??. Na?ae/aiiyi oeueiai i?ioeano ? ca?eueoaiiy
?ioaineaiino? ?icn?yiiy iiaeeco ia?aeiiiai ?aioaai?anueeiai i?iiaith (ye
?iaeeeaoi? e?eueeino? AAI a nenoai?) a ii??aiyii? c eiio?ieueiei c?aceii
eiiiiceoe?? IO-20AAI.

Eiiiiceoe?y IO-20AAI-6EAA ia? aeaoaeoio iae?i?ao?oeo a eiio?ieueiiio
c?aceo. Ia?aaoaaiiy oe??? eiiiiceoe?? in vivo 6 i?nyoe?a i?ecaiaeeoue
aei iiaiiai ?oeioaaiiy ye iae?i?ao?oee aei?noeeo aeiiai?a, oae ? naieo
aeiiai?a, ui iaoiiaeaii, ye ? o aeiaaeeo IO-20AAI, i?ioeanii iaeiie/aiiy
AAI a eiiiiceoe?? c iaeii/aniith a?iaeano?oeoe??th iie?ia?ii? iniiae.

Aeine?aeaeaiiy oaciai-e?enoae?/ii? no?oeoo?e iie?o?aoaio oa eiiiiceoe?e
ia eiai iniia? IO-20AAI, IO-20AAI-6EAA iieacaee, ui a?ae?ieneaiaoeo ia?
e?enoae?/io oaco, yea c?inoa? c? ca?eueoaiiyi /ano ia?aaoaaiiy in vivo.
I?i oea na?ae/eoue ca?eueoaiiy ?ioaineaiino? iniiaiiai aeeo?aeoe?eiiai
iaeneioia a?ae?ieneaiaoeoo (2 = 31,5 0 ) eiiiiceoe?e IO-20AAI oa
IO-20AAI-6EAA i?e 3-o ? 6-oe i?ny/i?e ?iieaioaoe??.

I?iaaaeai? aeine?aeaeaiiy i?aeoaa?aeeee oie oaeo, ui caoaa?ae?e?
iie?ia?i? eiiiiceoe??, ye? i?noyoue a nai?io neeaae? a?ae?ieneaiaoeo oa
eaaai?cie, a oiiaao in vivo iaeiie/othoue iai?aai?/io neeaaeiao, yea
iiaea neoaeeoe iniiaith aeey i?ioean?a e?noeiooai?aiiy a ?aaaia?oth/?e
oeaiei?.

A?io?i?/ia ? a?noieia?/ia oa?aeoa?enoeee niieo/iioeaieiii? ?aaeoe?? ia
iaiiaiai? a?ae?ieneaiaoeoii a?ieia?/ii aeoeai? iie?o?aoaiia? ?iieaioaoe

I?e ?iieaioaoe?? iie?ia?ieo iaoa??ae?a c a?ieia?/ii aeoeaieie
niieoeaie, ye? aeyaeythoue aaciina?aaei?e aieea ia ee?oeie ioi/oth/eo
oeaiei, iaiao?aeia i?iaaaeaiiy eiiieaeniiai aiae?co eainoe iaaeiei
?iieaioao?a aeey ia’?eoeaii? ioe?iee ?aaeoe?? aeeeeeaii? ?iieaioaoe??th.

Iaoith aeine?aeaeaiiy aoei ii??aiyeueia aea/aiiy a?io?i?/ieo ?
a?noieia?/ieo oa?aeoa?enoee oeaiei, ye? ioi/othoue iie?o?aoaiia?
eiiiiceoe?? c a?ae?ieneaiaoeoii oa ?ioiiiiaeoeyoi?ii – eaaai?cieii i?ae
/an ?o ?iieaioaoe??.

Aoei iieacaii (oaae. 4), ui ia 14-oo aeiao ia?aaoaaiiy a na?aaeiaeu?
i?aai?cio a?aeaoaa?oueny cia/ia ca?eueoaiiy aeoeaiino? eenei? oinoaoace
(EO) o niieo/iioeaieiieo eainoeao on?o aeine?aeieo c?ace?a o ii??aiyii?
c ii?iith (i?aeoe??ia ee?oeiaeia).

Oaaeeoey 4 – Aeoeai?noue EO a ioi/oth/eo ?iieaioao niieo/iioeaieiieo
eainoeao

EO, iiieue ia-1 oa-1Iaoa??aeIa??iae ?iieaioaoe??, aeiaa143090I?aeoe??ia
ee?oeiaeia15,0 + 1,5*21,0 + 2,7*18,0 + 1,2*IO35,2 + 2,6*26,8 + 2,6*22,9
+ 6,1*IO-6EAA47,9 + 3,4*28,9 + 2,5*31,4 + 5,5*IO-20AAI59,5 + 5,9*30,1 +
3,2*31,7 + 3,0*IO-20AAI-6EAA37,1 + 1,5*24,0 + 1,1*38,1 +
4,9**A?aei?iiino? o ii??aiyii? c ii?iith aeinoia??i? (p

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