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Розробка складу, технології та дослідження супозиторіїв і гелю метронідазолу у поєднанні з мебетизолом для комплексної терапії вагінальних інфекцій: А

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I?I?NOA?NOAI IOI?IIE CAeI?IAss OE?A?IE

CAII??CUeEEE AeA?AEAAIEE IAAeE*IEE OI?AA?NEOAO

NAE?E IEAIA IEAENAIAe??AIA

OAeE: 615.454.1/2.032.671:615.28.014.22

?IC?IAEA NEEAAeO, OAOIIEIA?? OA AeINE?AeAEAIIss

NOIICEOI???A ? AAETH IAO?II?AeACIEO O

II?AeIAII? C IAAAOECIEII AeEss EIIIEAENII?

OA?AI?? AAA?IAEUeIEO ?IOAEOe?E

15.00.01- oaoiieia?y e?e?a oa i?iieneiaa oa?iaoe?y

A a o i ? a o a ? a o

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa oa?iaoeaaoe/ieo iaoe

Caii??aeaey-1999

Aeena?oaoe??th ? ?oeiien.

?iaioa aeeiiaia ia eaoaae?? oaoiieia?? e?e?a Caii??cueeiai aea?aeaaiiai
iaaee/iiai oi?aa?neoaoo

Iaoeiaee ea??aiee: aeieoi? oa?iaoeaaoe/ieo iaoe, aeioeaio

Aeaaeeoaa A?oae?e Aaeaioeiiae/, Caii??cueeee aea?aeaaiee iaaee/iee
oi?aa?neoao, aeioeaio eaoaae?e oaoiieia?? e?e?a;

Io?oe?ei? iiiiaioe: aeieoi? oa?iaoeaaoe/ieo iaoe, i?ioani?

A?ioiaee Oa?an Aiae??eiae/, AO Aaee/oa?i (i. Euea?a), canooiiee
aee?aeoi?a c iaoeiai? ?iaioe oa ia?eaoeiao;

aeieoi? oa?iaoeaaoe/ieo iaoe, i?ioani? Nie?eaeiiia Aieiaeeie?
Ieeieaeiae/, Aea?aeaaiee iaoeiaee oeaio? e?ea?nueeeo cania?a (i.
Oa?e?a), caa?aeoaa/ eaai?aoi??? aeeoy/eo e?ea?nueeeo oi?i

I?ia?aeia onoaiiaa: Oe?a?inueea oa?iaoeaaoe/ia aeaaeai?y (i. Oa?e?a)

Caoeno a?aeaoaeaoueny 23 ea?oiy 1999 ?. i 12-00 aiae. ia can?aeaii?
niaoe?ae?ciaaii? a/aii? ?aaee E 17.600.01 o Caii??cueeiio aea?aeaaiiio
iaaee/iiio oi?aa?neoao? ca aae?anith: 330035, i. Caii??aeaey, i?ini.
Iayeianueeiai, 26.

C aeena?oaoe??th iiaeia iciaeiieoenue o iaoeia?e a?ae?ioaoe? iaaee/iiai
oi?aa?neoaoo (330035, i. Caii??aeaey, i?ini. Iayeianueeiai, 26).

Aaoi?aoa?ao ?ic?neaii 18 aa?aciy 1999 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? a/aii? ?aaee E 17.600.01 ?.N. Neiye

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

I?iaeaia e?eoaaiiy ?ioaeoe?eieo a?iaeieia?/ieo caoai?thaaiue ? iaei??th
c iaeneeaaei?oeo o na?oia?e iaaeeoeei? ? caeeoa?ony aeooaeueiith aeey
ioi?iie caei?ia’y ianaeaiiy Oe?a?ie. ?ioaeoe?eiiio caoai?thaaiith
o?iaai?oaeueieo i?aai?a a cia/i?e i??? ni?eythoue iaeiio?ieueiaaia
canoinoaaiiy aioea?ioee?a, ia?i?aeueieo eiio?aoeaioea?a,
aioeaiae?iaai?a, iio?aeieo i?iaanoa?iio, na?aae ?ioeo oaeoi??a –
o?ii?/i? caoai?thaaiiy ie?ie, ia/?iee, a oaeiae iani?eyoeaa? aeiiii?/i?
oa aeieia?/i? oiiae i?iaeeaaiiy. O eiiieaeni?e oa?ai?? oaeeo
caoai?thaaiue aaaeeeaa i?noea iin?aea? eieaeueia (i?noeaaa) canoinoaaiiy
e?ea?nueeeo cania?a o oi?i? noiiceoi???a, iacae, e?ai?a, aaa?iaeueieo
oaaeaoie, oaiiii?a, ?inoeeyoe?e.

Aeooaeuei?noue oaie. Aaa?iaeueiee oeyo aaaaeaiiy e?ea?nueeeo cania?a
ni?ey? aaciina?aaeiueiio aieeao aeoeaieo noanoaioe?e ia caoaeiee?a
caiaeueiiai ?ioaeoe?eiiai i?ioeano, noai?th? iiaeeea?noue ?aaoethaaiiy
aani?aoe??, cieaeaiiy nooiaiy oa iiaeeeaiai ?aoeeaeeao iaaaaeaieo
iia?/ieo aoaeo?a. Oaeaee?noue ianoaiiy oa?aiaaoe/ii? ae??, cae/i?noue ?
eiioi?oi?noue aaaaeaiiy oa aie?eaoe??, oieeiaiiy aieeao oa?iaio?a
oeoieiai-eeoeiaiai o?aeoo aeicaiey? a?aeianoe aaa?iaeuei? i?aia?aoe aei
iaea?eueo aoaeoeaieo ? aiaeii/an uaaeieo aei ae?ii/iai i?aai?cio cania?a
e?eoaaiiy caiaeueieo a?iaeieia?/ieo caoai?thaaiue.

?icoe?aiiy iiiaieeaoo?e oa ?ic?iaea no/anieo aaa?iaeueieo e?ea?nueeeo
oi?i a?oioo?oueny ia iioeiaeueiiio aeiai?? ae?th/eo ?a/iaei ?
oa?iaoeaaoe/ieo oaeoi??a c a?aooaaiiyi aiaoiii-o?c?ieia?/ieo
iniaeeainoae i?aai?cio ae?iie.

O ca’yceo c /anoi aeieeath/eie o?aaeaiiyie na/inoaoaaeo i?aai?a
anioe?aoe?yie iaoiaaiieo i?e?ii?aai?ci?a, ??ciiiai?oi?noth ee?i?/ieo
i?iya?a a?iaeieia?/ieo caoai?thaaiue, ?o ?aoeeaeeaaie c aeyaeaiiyi iiaeo
aaia?aoe?e caoaeiee?a ?ioaeoe?eiiai i?ioeanno, aeieea? iaiao?aei?noue
noai?aiiy oa canoinoaaiiy eiia?iiaaieo cania?a, ye? aieeaathoue
iaeii/anii ia ??ci? eaiee iaoiaaiaco. I?e oeueiio nai?/ania ao?o/aiiy o
aca?iia?aeiineie i?e?iaieo anioe?aoe?e ia neeciaeo iaieiieao
o?iaai?oae??a oeyoii i?ecia/aiiy ?aoe?iiaeueieo eiia?iiaaieo i?aia?ao?a
ia?aoeiaeaea? iaaaoeaiiio aieeao iiaiooai?thaaieo anioe?aoe?e ia i?ioean
aeaeoaeaiiy, onoaa? caa?ico ??ciiiai?oieo oneeaaeiaiue.

?ic?iaea aaa?iaeueieo e?ea?nueeeo oi?i c a?aeiiei i?ioei?ioicieiei
i?aia?aoii iao?ii?aeacieii o ii?aeiaii? c iaaaoecieii, yeee
a?aecia/a?oueny cia/iith aioeeaiaeeaeiciith aeoeai?noth, ni?eyoeia
?icoe?aiith a?naiaeo cania?a aoaeoeaiiai eiiieaeniiai e?eoaaiiy
eiia?iiaaieo ?ioaeoe?eieo o?aaeaiue o?iaai?oaeuei?o i?aai?a.
Aeaioiaeaiiy oaeeo cania?a a oiiaao aioaee /e oa?iaoeaaoe/iiai
ae?iaieoeoaa i?iieneiaeo i?aei?e?inoa Oe?a?ie cieceoue caeaaei?noue a?ae
aiaeia?/ieo ?iii?oiaaieo aaa?iaeueieo i?aia?ao?a.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie. Aeena?oaoe?eia
?iaioa aeeiiaia ca?aeii c ieaiii iaoeiai-aeine?aeieoeueei? oaie
Caii??cueeiai aea?aeaaiiai iaaee/iiai oi?aa?neoaoo (?a?no?aoe?eiee iiia?
0197O015663) ? ? o?aaiaioii iaoeiai-aeine?aeieoeueei? oaie IIC Oe?a?ie
(oeo? oaie 01.02.04/091.93).

Iaoa ? caaea/? aeine?aeaeaiiy. Iaoith ?iaioe ? iaoeiaa iaa?oiooaaiiy
neeaaeo ? oaoiieia?? aaa?iaeueieo noiiceoi???a ? aaeth c iao?ii?aeacieii
? iaaaoecieii aeey eiiieaenii? oa?ai?? caiaeueieo ?ioaeoe?eieo
caoai?thaaiue o?iaai?oaeueieo i?aai?a.

Aeey aeinyaiaiiy iinoaaeaiii? iaoe ae??ooaaeenue ianooii? caaea/?:

– ia i?aenoaa? aea/aiiy oaoiieia?/ieo, o?ceei-o?i?/ieo,
no?oeoo?ii-iaoai?/ieo aeanoeainoae iniia i?ae?a?aoe iioeiaeueiee neeaae
oa ?aoe?iiaeueio oaoiieia?th aaa?iaeueieo noiiceoi???a ? aaeth c
iao?ii?aeacieii ? iaaaoecieii;

– aea/eoe aieea oa?iaoeaaoe/ieo oaeoi??a ia a?ioa?iaoeaaoe/i? iieacieee
yeino? aaa?iaeueieo oi?i ?c caaaeaiith eiiiiceoe??th ?a/iaei a
aeine?aeao “in vitro” oa “in vivo”;

– aeine?aeeoe i?ioei?e?iai? aeanoeaino? eiiiiceoe?e iao?ii?aeacieo ?
iaaaoecieo oa i’yeeo aaa?iaeueieo e?ea?nueeeo oi?i c ieie;

– aecia/eoe iieacieee oa?iaeie?iaoeee oa a?ieia?/io aeinooii?noue
aeine?aeaeoaaieo ?a/iaei a aaa?iaeueieo e?ea?nueeeo oi?iao;

– ii?aoethaaoe oaoiieia?/i? noaie aeaioiaeaiiy ? iaoiaeeee
noaiaea?oecaoe?? aaa?iaeueieo oi?i c iao?ii?aeacieii o ii?aeiaii? c
iaaaoecieii;

– anoaiiaeoe noaa?euei?noue o?ceei-o?i?/ieo, i?e?ia?ieia?/ieo
aeanoeainoae, no?iee caa??aaiiy aaa?iaeueieo noiiceoi???a ? aaeth c
aeacaieie ?a/iaeiaie;

– neeanoe ?ioi?iaoe?ei? eenoe oa ?aoe?iiae?caoi?nuee? i?iiiceoe?? ia
neeaae ? niiniae aeaioiaeaiiy a?ae?a?aieo noaa?eueieo ? aoaeoeaieo
aaa?iaeueieo e?ea?nueeeo oi?i aeey e?eoaaiiy caiaeueieo ?ioaeoe?eieo
caoai?thaaiue o?iaai?oae??a.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. Ia iniia? a?ioa?iaoeaaoe/ieo,
?aieia?/ieo, o?ceei-o?i?/ieo, oa?iaeie?ia-oe/ieo aeine?aeaeaiue aia?oa
ii?aoeueiaai? iioeiaeueiee neeaae ? oaoiieia?y aaa?iaeueieo noiiceoi???a
? aaeth c ii?aeiaiiyi iao?ii?aeacieo ? iaaaoecieo ye cania?a
oe?eani?yiiaaii? i?ioei?e?iaii? ae??.

Aeyaeaiee o?niee aca?iica’ycie i?ae oa?iaoeaaoe/ieie oaeoi?aie –

i?e?iaeith aeiiii?aeieo ?a/iaei, aeaeii e?ea?nueei? oi?ie ? aeeiai?eith
aea?eueiaiiy oa a?ieia?/iith aeinooii?noth aeoeaieo eiiiiiaio?a o
aaa?iaeueieo caniaao.

Aeaaaeai? oeyoii iaoaiaoe/iiai iiaeaethaaiiy ??aiyiiy oa?iaeie?iaoeee
iao?ii?aeacieo ? iaaaoecieo a caeaaeiino? a?ae oeio ? aeaeo aaa?iaeueii?
oi?ie aeia?a ai?ieneiothoue aenia?eiaioaeuei? aeai? ? iiaeooue
aeei?enoiaoaaoenue aeey i?iaiicoaaiiy aoaeoeaiino? aaa?iaeueieo cania?a.
Anoaiiaeaii ?yae oa?iaeie?iaoe/ieo iieaciee?a ? nooi?iue a?ieia?/ii?
aeinooiiino? iao?ii?aeacieo c iaaaoecieii a caeaaeiino? a?ae e?ea?nueei?
oi?ie oa oeyoo ?? aaaaeaiiy.

I?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a. Ii?aoeueiaai? oaoiieia?/i?
noaie aeaioiaeaiiy oa iaoiaeeee ye?niiai ? e?euee?niiai aecia/aiiy
iao?ii?aeacieo ? iaaaoecieo o aaa?iaeueieo oi?iao oa a?ieia?/ieo
??aeeiao. Aeyaeaii, ui ii?aeiaiiy iao?ii?aeacieo ? iaaao?cieo o i’yeeo
aaa?iaeueieo eiiiiceoe?yo i?iyaey? a?eueo cia/io (?? ??‰???????????? ???????????yyy????.????1????????????? `@???&??yyyy?????Ayyy ????????????&? ?MathType??0????u?th??????Aeyaeaii, ui eiiiiceoe?y iao?ii?aeacieo c iaaaoecieii o ni?aa?aeiioaii? 1:1 i?iyaey? oe?ieee niaeo? aioea?eaeiai? oa aioeaaeoa?eaeueii? aeoeaiino?. E?ea?nuee? ? aeiiii?aei? ?a/iaeie, ye? aeei?enoiaoaaeenue i?e i?iaaaeaii? aeine?aeaeaiue a?aeiia?aeathoue aeiiaai ?nioth/i? ON, OON, /eiiei ia nueiaiaei? OO-O, AINO ? AeANO. A?ioa?iaoeaaoe/ia iaa?oiooaaiiy neeaaeo, oaoiieia?? oa aeine?aeaeaiiy aaa?iaeueieo noiiceoi???a c iao?ii?aeacieii o ii?aeiaii? c iaaaoecieii Aeine?aeaeaiiy i?iaaee ca?aeii noaie aeaiooaeoi?iiai aeenia?n?eiiai aiae?co c iiaoi?ieie aeine?aeaie (oaae. 1.). Aea/aee aieea noiiceoi?ieo iniia (oaeoi? A) ? iiaa?oiaai-aeoeaieo ?a/iaei ia iieacieee yeino? noiiceoi???a c ai?noii ii 0,15 a iao?ii?aeacieo ? iaaaoecieo. Aeaioiaeai? iaoiaeii aeeeaaiiy c?acee noiiceoi???a a?aeiia?aeaee aeiiaai ii?ioth/i? aeieoiaioaoe?? ia oaeo e?ea?nueeo oi?io. Oiio ia?aiao?ii iioei?caoe?? aoei aea?aii a?ioa?iaoeaaoe/iee iieaciee - aea?eueiaiiy aeoeaieo eiiiiiaio?a /a?ac iai?ai?iieeio iaia?aio. Aeenia?n?eiee aiae?c iaea?aeaieo aeaieo iieacaa, ui aeae iniiae-iin?y ? IA? cia/oua (?=0,05) aieeaa? ia ?ioaineai?noue aea?eueiaiiy (aeey oaeoi?a A: Faenia?. aeey iao?ii?aeacieo=24,8; Faenia?. aeey iaaaoecieo=212,3> Foaae.=4,05; aeey
oaeoi?a A: Faenia?. aeey iao?ii?aeacieo=18,3; Faenia?. aeey
iaaaoecieo=167,5>Foaae.=5,04).

Ia?aa??ea ??cieoe? na?aaei?o cia/aiue aeey iaio cia/oueo oaeoi??a ca
aeiiiiiaith iiiaeeiiiai ?aiaiaiai e?eoa??th Aeoieaia aeicaieeea neeanoe
?yaee aieeao iniiae ? IA? ia aea?eueiaiiy iao?ii?aeacieo: a3(a4)>a2>a1
oa a2(a1)>a3>a4; ia aea?eueiaiiy iaaaoecieo a4(a3)>a1>a2 oa a2>a1>a3>a4.

Ianooiia aea/aiiy aeeiai?ee aea?eueiaiiy aeoeaieo eiiiiiaio?a ?c
noiiceoi???a ia a?ae?io?euei?e oa e?iio?euei?e iniiaao iieacaei, ui
noiiceoi??? ia iie?aoeeaiieneaei?e iniia? c aeiaeaoeii 1% aioeueaaoi?a
?1

Oaaeeoey 1.

Iao?eoey ieaioaaiiy ? ?acoeueoaoe aecia/aiiy eiioeaio?aoe?? (iea/ie)
aea?eueiaieo iao?ii?aeacieo (?) ? iaaaoecieo (??) ?c noiiceoi???a

(?ioa?aae – 60 oa.)

Oaeoi? Oaeoi? A- aeae IA?A-aeae

iniiaea1

oa?i-80a2

aioeuea. ?1a3

IAAea4

aac IA?????????????a1
-663,0173,0663,0178,0591,0130,0335,0126,0oaa?ae.632,5162,0636,0169,0629,
0137,0343,0131,0aee?647,5179,0789,0173,0610,0128,0365,0123,0a2-caaiae.60
9,5141,0785,0149,0571,5137,0327,5121,0aee?iaa.762,0153,0800,0143,0603,01
50,0422,5129,0iniiaa686,0138,0775,0141,0557,0141,0371,0137,0a3 –
IAI632,0208,0761,9229,0723,8184,0838,1145,0iniiaa
?636,2214,0723,8231,0647,6173,0876,2137,0640,0201,0746,7228,0666,7196,09
14,3149,0a4 –
IAI1015,0211,0731,4221,0742,9191,0857,1138,0inii-1055,0219,0731,4219,074
2,9203,0887,6145,0aa ??986,7216,0773,3223,0769,5183,0841,9151,0

ca aaee/eiith eiinoaioe oaeaeeino? aea?eueiaiiy iathoue nooo?ao ia?aaaao
ia?aae e?ea?nueeith oi?iith ia oaa?aeiio aee??.

?aieia?/ieie aeine?aeaeaiiyie aoei anoaiiaeaii, ui aeey noiiceoi?ieo ian
ia iie?aoeeaiieneaei?e iniia? a?aie/ia iai?oaeaiiy aeaoi?iaoe?? iaeaea o
6 ?ac?a ia?aaeuo? oeth aaee/eio aeey e?iio?eueieo nenoai. O ia??iae
ciyooy iai?oae aeaoi?iaoe?? noiiceoi?i? iane ia IAI-iniia? oaeaeei
a?aeiiaeththoue a’ycei-ieanoe/i? aeanoeaino?, ui i?aeoaa?aeaeo? ?o
aenieo no?oeoo?iaai?noue, i?iaiico? noaa?euei?noue aei iaoai?/ieo
?oeioaaiue i?e o?ainii?ooaaii?, caa??aaii? oa i?aeoe/iiio canoinoaaii?.

Ca aaee/eiaie cii cao?eiee ?inoo iaoiaaiieo aaeoa??e ? a?ea?a
noiiceoi??? c iao?ii?aeacieii ? iaaaoecieii ia IAI-iniia? iathoue
noaoenoe/ii aeinoia??io ia?aaaao ia?aae noiiceoi??yie ia oaa?aeiio aee??
c oaeei aea ii?aeiaiiyi aeoeaieo ?a/iaei.

Neeaaeaia oaoiieia?/ia noaia ae?iaieoeoaa aaa?iaeueieo noiiceoi???a
a?aeiia?aeii aei aeiia INO 42-O-2-92 ? i?iaaaeaia noaiaea?oecaoe?y
aeaioiaeaii? e?ea?nueei? oi?ie. Iniiai? iieacieee yeino? noiiceoi???a,
ai?no ae?th/eo ?a/iaei, a?ioa?iaoeaaoe/i? oa?aeoa?enoeee ? aioei?e?iaia
aeoeai?noue ?noi/ii ia ci?iththoueny i?ioyaii 24 i?nyoe?a
caa??aaiiy (i?e e?iiaoi?e oaiia?aoo??).

A?ioa?iaoeaaoe/ia iaa?oiooaaiiy neeaaeo ? oaoiieia?? oa aeine?aeaeaiiy
aaa?iaeueiiai aaeth c iao?ii?aeacieii ? iaaaoecieii

Aaa?iaeuei? aae? oa iac? a?aeiinyoueny aei iaea?eueo uaaeieo ? aiaeii/an
aoaeoeaieo cania?a eiiieaeniiai e?eoaaiiy caoai?thaaiue
o?iaai?oae??a,

iniaeeai o in?a noa?oiai a?eo, a oaeiae ae?oae oa i?aee?oe?a.

sse iin?? aeey aaa?iaeueiiai aaeth aeine?aeeee eiiiiceoe?? aeiiii?aeieo
?a/iaei – no?oeoo?oth/eo, iiaa?oiaai-aeoeaieo, a?ae?io?e?coth/eo
?ic/eiiee?a, ye? i?aeaeuothoue noaa?euei?noue nenoai, ciaioothoue
caeaoi?noue aei aeneoaiiy, caaacia/othoue oaeiae c?o/i?noue aie?eaoe??
oa cieaaiiy. Eiioeaio?aoe?y iao?ii?aeacieo ? iaaaoecieo o aaeaaeo
eiiiiceoe?yo neeaaeaea 1,5%, ui caaacia/oaaei ca?aeii iiia?aaei?i
i?e?ia?ieia?/iei aeine?aeaeaiiyi iaea?eueoo i?ioei?e?iaio aeoeai?noue.
Aeey iaeii/aniiai aa??thaaiiy on?ia oaeoi?aie, nei?i/aiiy ia?aai?o
aeine?ae?a an? aenia?eiaioe i?iaiaeeee ca noaiith eaoeinueeiai eaaae?aoo
4o4. Aeaioiaeai? a iaeiaeiaeo oiiaao eiiiiceoe?? aaeth ca ye?nieie
iieacieeaie a?aeiia?aeaee aeiiaai AeO O? aeae. Aea/aiiy aeeiai?ee
aea?eueiaiiy iao?ii?aeacieo ? iaaaoecieo /a?ac ae?ae?cio iaia?aio
eoi?ioai (c aia?aoo ooo/ia ie?ea) aei aiaeiiai na?aaeiaeua c ??ciei
cia/aiiyi ?I (?en.1.) aeicaieeei ae??cieoe aaeaa? eiiiiceoe?? ? 8 ? 9.
Iniiae ae?oea?iaaeth iao??th ea?aieneiaoeeoeaetheice (i?iien ? 8 ia
ae?aa?ai?) oa iaeoeio yaeo/iiai (i?iien ? 9 ia ae?aa?ai?) caaacia/oaaee
naiee aenieee ??aaiue aea?eueiaiiy aeoeaieo eiiiiiaio?a. Aeenia?n?eiee
aiae?c ?acoeueoao?a aea?eueiaiiy, iaaaaeaieo o ae?aa?ai?, i?aeoaa?aeea
cia/ou?noue aieeao no?oeoo?iooai?thth/eo ? a?ae?io?e?coth/eo
aeiiii?aeieo ?a/iaei ia oeae a?ioa?iaoeaaoe/iee iieaciee yeino?
e?ea?nueei? oi?ie.

Aeey ia’?eoeaiino? ioe?iee aaeth ia ??cieo iniiaao ? aaeth-ieaoeaai
anoaiiaethaaee ?o no?oeoo?ii-iaoai?/i? oa?aeoa?enoeee. ?acoeueoaoe
aea/aiiy caeaaeiino? aaee/eie aoaeoeaii? a’yceino? ? a?aie/iiai
iai?oaeaiiy cnoao a?ae oaeaeeino? aeaoi?iaoe?? iieacaee, ui a’yce?noue o
aeine?aeaeoaaieo nenoaiao ??cei cieaeo?oueny ?c c?inoaiiyi
aeaoi?iaoe?eieo nee. O ia??iae ciaioaiiy i?eeeaaeaii? iai?oae a’yce?noue
iino?eii a?aeiiaeth?oueny, ui i?aeoaa?aeaeo? no?oeoo?iaai?noue aaeaaeo
eiiiiceoe?e, iaoiiaeaieo iayai?noth eiaaoeyoe?eieo ca’yce?a c aeineoue
iaeei ia??iaeii ?aeaenaoe?eiiai /ano. ?aieia?/i? oa?aeoa?enoeee
aae?a-ieaoeaai nooo?ai ia a?ae??ciythoueny a?ae eiiiiceoe?eieo aae?a c
iao?ii?aeacieii ? iaaaoecieii. Aaee/eie iaoai?/ii? noaa?eueiino?
ii??aithaaieo aae?a ia aeaio iniiaao a?ae??ciythoueny iacia/ii.

1-19,5%

2-17,1%

3-15,3%

4-21,9%

5-59,5%

6-57,2%

7-32,0%

8-61,1%

9-53,7%

10-49,9%

11-30,5%

12-50,4%

13-40,5%

14-37,0%

15-33,4%

16-42,7%

?

1-6,8%

2-5,2%

3-3,8%

4-7,1%

5-24,1%

6-21,3%

7-18,1%

8-36,3%

9-24,1%

10-21,3%

11-17,2%

12-20,0%

13-12,3%

14-11,4%

15-9,7%

16-14,0%

??

?en. 1. Ae?aa?aie ?ioaineaiino? aea?eueiaiiy (%) iao?ii?aeacieo (?) oa
iaaaoecieo (??) c eiiiiceoe?e (1-16) aaa?iaeueieo aae?a i?ioyaii 30 oa.

Aeey e?ioeaaiai aecia/aiiy ia?aaaa aaeth c iao?ii?aeacieii ? iaaaoecieii
ia ??cieo iin?yo i?iaaee ?o i?e?ia?ieia?/ia aeine?aeaeaiiy o ii??aiyii?
c aeayeeie i?aia?aoaie-aiaeiaaie. Anoaiiaeaii, ui aaeue ia iniia?
iao??th ea?aieneiaoeeoeaetheice c aeiaeaoeaie IAI400 ? aeeiaeneaeo
i?iyaey? aeinoia??ii (?? ??‰???????????? ???????????yyy????.????1????????????? ?@???&??yyyy?????Ayyyayyy???`?????&??MathType?? ????u?th??????Nt(I?)=125,0exp(-0,36t)-exp(-9,5t), aea twmetafile8? ??‰???????????? ???????????yyy????.????1?????? ????????@???&??yyyy?????Ayyyayyy???`?????&??MathType?? ????u?th??????aeey aaa?iaeueiiai aaeth Iao?icieue: Nt(I)=180,0exp(-0,61t)-exp(-5,82t), aea twmetafile8? ??‰???????????? ???????????yyy????.????1?????? ????????@???&??yyyy?????Ayyyayyy???`?????&??MathType?? ????u?th??????Nt(I?)=130,0exp(-0,38t)-exp(-7,2t), aea twmetafile8? ??‰???????????? ???????????yyy????.????1?????? ????????@???&??yyyy?????Ayyyayyy???`?????&??MathType?? ????u?th????????aiyiiy ia iniia? iaeii/anoeiii? iiaeae? c aniieooaaiiyi caaeia?eueii ai?ieneiothoue ?acoeueoaoe aenia?eiaioaeueieo aecia/aiue eiioeaio?aoe?? iao?ii?aeacieo ? iaaaoecieo o ne?iaaooe? e?ia?. Ii??aiyeueiee aiae?c ia?aiao??a oa?iaeie?iaoeee iao?ii?aeacieo ? iaaaoecieo cana?ae/ea, ui i?ney aaa?iaeueiiai canoinoaaiiy noiiceoi???a ? aaeth iaeaea? ?a/iaeie aeineoue aeia?a ?ici?eae?eythoueny ? iane/othoue o?c?ieia?/i? ??aeeie. Nooi?iue a?aeiinii? a?iaeinooiiino? iaio ?a/iaei o oi?i? noiiceoi???a - 109%, o oi?i? aaeth - 115,4% (iao?ii?aeacie) ? 105,2% (iaaaoecie). I?aeoaa?aeaeaia a?aenooi?noue i?noeaaiiiae?acithth/i? oa aea?a?coth/i? ae?? ii?aoeueiaaieo e?ea?nueeeo oi?i, ye? o aenia?eiaio? ia aeeeeeaee a?aeoeeaiue a?ae ii?ie iniiaieo ia?aiao??a aeeoo?ae?yeueiino? aeine?aeieo oaa?ei, ia ni?e/eithaaee ci?i iae?i- ? i?e?ineii?/ii? aoaeiae i?aai?a ? oeaiei. Noiiceoi??? O?eoicie ? aaeue Iao?icieue i?iyaeyee ae?aciee oa?aiaaoe/iee aoaeo ia iiaeaeyo aaa?i?oo uo??a ? o?eoiiiiaaeiiai aanoeano eaai?aoi?ieo ieoae. AENIIAEE 1. Ia iniia? eiiieaenieo oaoiieia?/ieo, a?ioa?iaoeaaoe/-ieo, o?ceei-o?i?/ieo oa a?ieia?/ieo aeine?aeaeaiue ?ic?iaeai? iioeiaeueiee neeaae ? oaoiieia?y aaa?iaeueieo noiiceoi???a ? aaeth c iao?ii?aeacieii o ii?aeiaii? c iaaaoecieii, ye? a?aecia/athoueny noaa?euei?noth, iaoe?aeeea?noth, niaoeeo?/iith aeoeai?noth ii a?aeiioaiith aei caoaeiee?a ?ioaeoe?eieo caoai?thaaiue o?iaai?oae??a. 2. ?ic?iaeai? iaoiaeeee e?euee?niiai aecia/aiiy ii?aeiaiue iao?ii?aeacieo ? iaaaoecieo o i’yeeo ? oaa?aeeo e?ea?nueeeo oi?iao, o?c?ieia?/ieo ??aeeiao - ne?iaaooe? e?ia?, aaa?iaeueiiio nae?ao? oa ?io?. Iaoiaeeee a?aecia/athoueny aeia?ith a?aeoai?thaai?noth oa /ooeea?noth; a?aeiinia iiieeea aecia/aia o e?ea?nueeeo oi?iao ciaoiaeeoueny o iaaeao 0,7-1,19%, o o?c?ieia?/ieo ??aeeiao - 1,5-2,67%. 3. A?ioa?iaoeaaoe/ieie aeine?aeaeaiiyie in vitro anoaiiaeaii nooo?aee aieea iie?aoeeaiieneaeii? iniiae c aeiaeaoeii aioeueaaoi?a ? 1 ia ?ioaineai?noue aea?eueiaiiy iao?ii?aeacieo ? iaaaoecieo c aaa?iaeueieo noiiceoi???a. ?ic?iaeaii oaoiieia?th, neeaaeaii ae?iaie/o noaio aeaioiaeaiiy aaa?iaeueieo noiiceoi???a O?eoicie (iao?ii?aeacie:iaaaoecie ye 1:1), ye? caaacia/othoue aeione ye?nii? e?ea?nueei? oi?ie. 4. Ii?aoeueiaaii neeaae ? oaoiieia?th aaa?iaeueiiai aaeth c 1,5% ai?noii iao?ii?aeacieo ? iaaaoecieo (aaeue Iao?icieue), yeee oa?aeoa?eco?oueny noaa?euei?noth o?ceei-o?i?/ieo aeanoeainoae i?e caa??aaii?, ?ioaineai?noth aea?eueiaiiy ae?th/eo ?a/iaei ? iiai?noth a?aeiia?aea? aeiiaai ?nioth/i? ii?iaoeaii? aeieoiaioaoe?? aeey i’yeeo e?ea?nueeeo oi?i. 5. Aea/ai? ?aieia?/i? aeanoeaino? aaa?iaeueieo noiiceoi???a ? aaeth c iao?ii?aeacieii ? iaaaoecieii. No?oeoo?e ooai?aieo oeenio?iiieo nenoai oa?aeoa?ecothoueny a?aeiiaethaaieie eiaaoeyoe?eieie ca’yceaie, iioeiaeueieie no?oeoo?ii-iaoai?/ieie oa?aeoa?enoeeaie, ye? i?iaiicothoue noaa?euei?noue oeeo nenoai a oiiaao ae?iaieoeoaa, caa??aaiiy oa canoinoaaiiy. 6. A ii??aiyeueieo i?e?ia?ieia?/ieo aeine?aeaeaiiyo aaa?iaeuei? noiiceoi??? oa aaeue c iao?ii?aeacieii ? iaaaoecieii i?iyaeythoue ae?acio i?ioea?eaeiao, i?ioenoioeeaeio ? aioeaaeoa??aeueio aeoeai?noue. Aaa?iaeuei? noiiceoi??? O?eoicie ia iie?aoeeaiieneaei?e iniia? ca aaee/eiaie cii cao?eiee ?inoo eaiae?aee, i?ioay, aio?aei?aea, noao?eieiea o 2,5-3,0 ?ace ia?aaeuothoue ?acoeueoaoe aeey oaeeo aea noiiceoi???a ia iniia? oaa?aeiai aee?o. Aaa?iaeueiee aaeue Iao?icieue ca i?ioea?eaeiaith oa aioeaaeoa??aeueiith aeoeai?noth aeinoia??ii ia?aaeuo? aeoeai?noue a?aeiieo ?iii?oiaaieo aiaeia?a - i?ci?aeiaiai oa eeio?eiacieiaiai e?ai?a. 7. Ia i?aenoaa? a?ioa?iaoeaaoe/ieo aeine?aeaeaiue in vivo oeyoii iaoaiaoe/iiai iiaeaethaaiiy aenia?eiaioaeueieo ?acoeueoao?a aecia/ai? oa?iaeie?iaoe/i? ia?aiao?e ? a?ieia?/ia aeinooii?noue iao?ii?aeacieo ? iaaaoecieo o aaa?iaeueieo e?ea?nueeeo oi?iao. Eiinoaioe oaeaeeino? aniieooaaiiy, ae?i?iaoe??, noaoe?iia?iiai ia’?io ?ici?eae?eaiiy, ieaciaoe/iiai ee??aino oa ?io? i?aeoaa?aeaeothoue ??aiii??ia ?ici?eae?eaiiy ? iiaia iane/aiiy o?c?ieia?/ieo ??aeei ? oeaiei aeeaiai i?aai?cio aeoeaieie eiiiiiaioaie i?ney aaa?iaeueiiai aaaaeaiiy noiiceoi???a ? aaeth c iao?ii?aeacieii ? iaaaoecieii. A?aeiinia a?ieia?/ia aeinooii?noue oeeo ?a/iaei o oi?i? noiiceoi???a noaiiaeoue 109,0-109,7%, o oi?i? aaeth - 105-115%, ui aeiaeaoeiai i?aeoaa?aeaeo? iioeiaeuei?noue cai?iiiiiaaiiai neeaaeo ? oaoiieia?? e?ea?nueeeo oi?i. 8. A aenia?eiaioaeueieo oa?iaeieia?/ieo aeine?aeao aeieacaia a?aenooi?noue i?noeaaiiiae?acithth/i? oa aea?a?coth/i? ae?? ii?aoeueiaaieo aaa?iaeueieo e?ea?nueeeo oi?i c iao?ii?aeacieii ? iaaaoecieii. Noiiceoi??? O?eoicie ? aaa?iaeueiee aaeue Iao?icieue i?iyaeythoue ae?aciee oa?aiaaoe/iee aoaeo ia iiaeae? aaa?i?oo uo??a ? o?eoiiiiaaeiiai aanoeano eaai?aoi?ieo ieoae. 9. Ca ?acoeueoaoaie i?iaaaeaieo aeine?aeaeaiue i?aeaioiaeai? oa ai?iaaaeaeai? a i?aeoeeo oa?iaoeaaoe/ieo ae?iaieoeoa aeaa ?ioi?iaoe?eieo eenoa i?i neeaae ? oaoiieia?th aaa?iaeueieo noiiceoi???a ? aaeth aeey eiiieaeniiai e?eoaaiiy caiaeueieo ?ioaeoe?eieo caoai?thaaiue o?iaai?oae??a. Iaea?aeaii aeaa na?aeioeoaa ?aoei?iiiceoe?e ia niiniae aeaioiaeaiiy oa ?aoeaioo?o aaa?iaeueieo e?ea?nueeeo cania?a c iao?ii?aeacieii ? iaaaoecieii, ye? ai?iaaaeaeai? a ?iaioo aioae, o/aiaee i?ioean ?ioa?i?a-i?ia?ci??a ? nooaeaio?a oa?iaoeaaoe/ieo aoc?a. NIENIE IIOAE?EIAAIEO I?AOeUe CA OAIITH AeENA?OAOe?? 1. Nae?e I.I. Ii??aiyeueia oa?aeoa?enoeea no?oeoo?ii-iaoai?/ieo aeanoeainoae eiiiiceoe?e aae?a c iaaaoecieii oa iao?ii?aeacieii // Oa?i. aeo?iae. - 1997. - ? 3. - N. 78-81. 2. Nae?e I.I., Aieiae?i A.A. ?ic?iaea oa aeine?aeaeaiiy aaa?iaeueieo noiiceoi???a c iao?ii?aeacieii oa iaaaoecieii // Aeo. ieoaiiy oa?i. oa iaae. iaoee ? i?aeoeee: Na. iaoe. noao. - Caii??aeaey, 1997. - Aei. 1. - N. 123-126. 3. Nae?e I.I. I?i ei?aeyoe?eio caeaaei?noue ?acoeueoao?a a?ioa?iaoeaaoe/ieo oa oa?iaeie?iaoe/ieo aeine?aeaeaiue eiia?iiaaieo noiiceoi???a c iao?ii?aeacieii // Aeo. ieoaiiy oa?i. oa iaae. iaoee ? i?aeoeee: Na. iaoe. noao. - Caii??aeaey, 1999. - Aei. 3. - N. 67-70. 4. I?i ?icoe?aiiy a?naiaeo e?ea?nueeeo cania?a aeey oa?ai?? caoai?thaaiue, ye? ia?aaeathoueny noaoaaei oeyoii / A.I. Oaaeioia, A.A. Aieiae?i, A.A. Aeaaeeoaa, ?.I. Iooaeuenueea, I.I. Nae?e // O?oaeu iaae?aaeiiaeueiie iao/i.-i?aeo. eiioa?aioeee o?ieiaia. - Caii?iaeuea, 1995. - N. 72. 5. Nae?e I.I., Aeaaeeoaa A.A., Noaoe A.?. Aeaye? iniaeeaino? a?ioa?iaoeaaoe/ieo aeine?aeaeaiue iiaeo e?ea?nueeeo oi?i a oa?ai?? aea?iaoio?o?e // Aeo. ieoaiiy oa?i. iaoee oa i?aeoeee: Iao-ee iaae?aa?iiaeueii? iaoee.-i?aeo. eiio. - Caii??aeaey, 1995. - N. 119-120. 6. Naeee A.A., Aeaaeuoaa A.A., Aonaeiaa A.A. ?ac?aaioea e enneaaeiaaiea aaeaauo eiiiiceoeee iao?iieaeaciea e iaaaoeciea // Aeo. aii?inu aea?iaoi-aaia?ieiaee: iao/.-i?ae. nai?iee. - Aeiai?iiao?iane-Oiaeueieoeeee, 1996. - N. 130. 7. Naeee A.A., Aieiaeei A.A., Aeaaeuoaa A.A. Aeioa?iaoeaaoe-/aneia e ?aieiae/aneia enneaaeiaaiea aaaeiaeueiiai aaey O?eoicie // Na. iao/. o?oaeia. - Caii?iaeuea, 1996. N. 97-98. 8. Naeee A.A., Aeaaeuoaa A.A. Aeioa?iaoeaaoe/aneia eco/aiea aaaeiaeueiuo noiiceoi?eaa, niaea?aeaueo iao?iieaeacie a ni/aoaiee n iaaaoecieii // Aeo. aii?inu aea?iaoi-aaia?ieiaee: iao/.-i?ae. nai?iee. - Aeiai?iiao?iane-Oiaeueieoeeee, 1997. - N. 64. 9. Nae?e I.I., Aeaaeeoaa A.A., Aieiae?i A.A. Aeaioiaeaiiy aaa?iaeueieo aae?a ca iaa?no?aeueieie i?iienaie aeey eiiieaeniiai e?eoaaiiy caiaeaiue aaeoa??aeueiiai oa a?eaeiaiai iioiaeaeaiiy // ?ioi?iaoe?eiee eeno ? 27-97. - Ee?a: Oe?iaaeiaoaio?ioi?i IIC Oe?a?ie. - 1997. 10. Nae?e I.I., Aeaaeeoaa A.A., Aieiae?i A.A. Iaoiaee aeaioiaeaiiy eiia?iiaaieo noiiceoi???a O?eoicie aeey aaa?iaeueiiai canoinoaaiiy // ?ioi?iaoe?eiee eeno ? 54-97. - Ee?a: Oe?iaaeiaoaio?ioi?i IIC Oe?a?ie. - 1997. Nae?e I.I. ?ic?iaea neeaaeo, oaoiieia?? oa aeine?aeaeaiiy noiiceoi???a ? aaeth iao?ii?aeacieo o ii?aeiaii? c iaaaoecieii aeey eiiieaenii? oa?ai?? aaa?iaeueieo ?ioaeoe?e. - ?oeiien. Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa oa?iaoeaaoe/ieo iaoe ca niaoe?aeuei?noth 15.00.01 - oaoiieia?y e?e?a oa i?iieneiaa oa?iaoe?y. - Caii??cueeee aea?aeaaiee iaaee/iee oi?aa?neoao, Caii??aeaey, 1999. Aeena?oaoe?th i?enay/aii noai?aiith iioeiaeueiiai neeaaeo ? oaoiieia?? aaa?iaeueieo noiiceoi???a ? aaeth c iao?ii?aeacieii ? iaaaoecieii. Aeine?aeaeai? ??ci? a?oie aeiiii?aeieo ?a/iaei ? niiniae aeaioiaeaiiy aeacaieo i’yeeo e?ea?nueeeo oi?i. ?ic?iaeai? iaoiaeeee aecia/aiiy iao?ii?aeacieo o ii?aeiaii? c iaaaoecieii o noiiceoi??yo, aaeyo, a?ieia?/ieo ??aeeiao - ne?iaaooe? e?ia?, aaa?iaeueiiio nae?ao?, neei?. Aea/ai? iaoe?aeeea?noue, niaoeeo?/ia aeoeai?noue ?ic?iaeaieo aaa?iaeueieo noiiceoi???a ? aaeth, a oaeiae ?o noaa?euei?noue ? i?ioei?e?iaia aeoeai?noue o i?ioean? caa??aaiiy. Neeaaeai? ? ai?iaaaeaeai? a i?aeoeeo ?ioi?iaoe?ei? eenoe ? ?aoei?iiiceoe?? ia neeaae ? aeaioiaeaiiy i’yeeo e?ea?nueeeo oi?i aeey eiiieaenii? oa?ai?? aaa?iaeueieo ?ioaeoe?eieo caoai?thaaiue. Eeth/ia? neiaa: iao?ii?aeacie, iaaaoecie, noiiceoi???, aaeue, aaa?iaeuei? caniae, oaoiieia?y, a?ioa?iaoeaaoe/i? aeine?aeaeaiiy, noaa?euei?noue. Naeee A.A. ?ac?aaioea ninoaaa, oaoiieiaee e enneaaeiaaiea noiiceoi?eaa e aaey iao?iieaeaciea a ni/aoaiee n iaaaoecieii aeey eiiieaeniie oa?aiee aaaeiaeueiuo eioaeoeee - ?oeiienue. Aeenna?oaoeey a aeaea ?oeiiene ia nieneaiea iao/iie noaiaie eaiaeeaeaoa oa?iaoeaaoe/aneeo iaoe ii niaoeeaeueiinoe 15.00.01 - oaoiieiaey eaea?noa e i?iiuoeaiiay oa?iaoeey. - Caii?iaeneee ainoaea?noaaiiue iaaeeoeeineee oieaa?neoao, Caii?iaeuea, 1999. Aeenna?oaoeey iinayuaia nicaeaieth iioeiaeueiiai ninoaaa e oaoiieiaee aaaeiaeueiuo noiiceoi?eaa e aaey n iao?iieaeacieii e iaaaoecieii. Eco/aiu ?acee/iua a?oiiu aniiiiaaoaeueiuo aauanoa e niiniau i?eaioiaeaiey oeacaiiuo iyaeeo eaea?noaaiiuo oi?i. Aeioa?iaoeaaoe/aneeie enneaaeiaaieyie in vitro onoaiiaeaii cia/eoaeueiia aeeyiea iieeyoeeaiieneaeiie iniiau n aeiaaaeaieai yioeueaaoi?a ? 1 ia eioaineaiinoue aunaiaiaeaeaiey iao?iieaeaciea e iaaaoeciea ec aaaeiaeueiuo noiiiceoi?eaa. ?ac?aaioai iioeiaeueiue ninoaa e niinia i?eaioiaeaiey aaaeiaeueiiai aaey n 1,5% niaea?aeaieai iao?iieaeaciea e iaaaoeciea, eioi?ue ioaa/aao o?aaiaaieyi nouanoaothuae ii?iaoeaiie aeieoiaioaoeee ia iace e iaania/eaaao ?aaiiia?iia aunaiaiaeaeaiea aeaenoaothueo aauanoa. Ia iniiaaiee ?ac?aaioaiiuo oaoiieiaee ninoaaeaiu i?iecaiaenoaaiiua noaiu ecaioiaeaiey aaaeiaeueiuo noiiceoi?eaa O?eoicie e aaaeiaeueiiai aaey Iao?icieue. ?ac?aaioaiu iaoiaeeee eiee/anoaaiiiai ii?aaeaeaiey iao?iieaeaciea a ni/aoaiee n iaaaoecieii a noiiceoi?eyo, aaeyo, aeieiae/aneeo aeeaeeinoyo - nuai?ioea e?iae, aaaeiaeueiii nae?aoa e nethia, eioi?ua oa?aeoa?ecothony /oanoaeoaeueiinoueth e i?inoioie aini?iecaaaeaiey. Eco/aiu ?aieiae/aneea naienoaa aaaeiaeueiuo noiiceoi?eaa e aaey n iao?iieaeacieii e iaaaoecieii. No?oeoo?u ia?aciaaiiuo oeenio?iiiuo nenoai oa?aeoa?ecothony ainnoaiiaeaiiuie eiaaoeyoeeiiiuie naycyie, iioeiaeueiuie no?oeoo?ii-iaoaie/aneeie oa?aeoa?enoeeaie, eioi?ua i?iaiice?otho noaaeeueiinoue yoeo nenoai a oneiaeyo i?iecaiaenoaa, o?aiaiey e i?eiaiaiey. A ?acoeueoaoa iee?iaeieiae/aneeo enneaaeiaaiee onoaiiaeaia aunieay i?ioeaia?eaeiaay, i?ioeaii?inoaoeeaeiay e aioeaaeoa?eaeueiay aeoeaiinoue ?ac?aaioaiiuo noiiceoi?eaa e aaey. Onoaiiaeaiu oneiaey e n?iee o?aiaiey aaaeiaeueiuo eaea?noaaiiuo oi?i, eioi?ua iaania/eaatho noaaeeueiinoue i?aaiieaioe/aneeo, oeceei-oeie/aneeo e iee?iaeieiae/aneeo naienoa. Eco/aiu aaca?aaeiinoue e niaoeeoe/aneay aeoeaiinoue ?ac?aaioaiiuo aaaeiaeueiuo noiiceoi?eaa e aaey. Ninoaaeaiu e aiaae?aiu a i?aeoeeo eioi?iaoeeiiiua ienueia e ?aoei?aaeeiaeaiey ii ninoaao e i?eaioiaeaieth iyaeeo eaea?noaaiiuo oi?i aeey eiiieaeniie oa?aiee aaaeiaeueiuo eioaeoeeiiiuo caaieaaaiee. Eeth/aaua neiaa: iao?iieaeacie, iaaaoecie, noiiiceoi?ee, aaeue, aaaeiaeueiia n?aaenoai, oaoiieiaey, noaaeeueiinoue, aeioa?iaoeaaoe/aneea enneaaeiaaiey. Saliy H.A. Working out of composition, technology and analyses of suppositories and get of metronidazole in combination with mebetizolum for complex therapeutics of vaginal infections. - Manuscript. The thesis in the form of manuscript for obtaining the scientific degree of candidate of pharmacy in speciality 15.00.01 - technology of drugs and manufacture farmacie. Zaporozhian state medical university, Zaporozhye, 1999. Thesis is devoted to creation of optimal composition and technology of vaginal suppositories and gel with methronidazole and mebetizolum. Different groups of supplementary substances and ways of preparing of mentioned soft medical forms have been studied. Methodics of determination of methronidazole in combination with mebetizolum suppositories, gels, biological liquids - in blood serum, vaginal secretion and saliva have been worked out. Innocuous, special activity of laborated vaginal suppositories and gel, their stability and antiallergical activity in helping have been studied. Informational letters and rational suggestions concerning of soft medical forms for complex therapeutics of vaginal infectious diseases have been composed and inculcate on practice. Key words: metronidazole, mebetizolum, suppositories, gel, vaginal remedies, technology, stability, biopharmaceutical investigations. AAOI?AOA?AO I?aeienaii aei ae?oeo 11.02.99. Oi?iao 60o84/32. Iai?? ionaoiee. Oiia. ae?oe. a?e. 1. Oe?aae 100 i?. Cai. ? 319. Iaae?oeiaaii a oeiia?ao?? ?IE Caii?iaeuea, 330095, i. Caii??aeaey, i?. Eai?ia, 152.

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