LV12177B - Antiglikokortikoīdu dabas ārstnieciskais līdzeklis - Google Patents

Antiglikokortikoīdu dabas ārstnieciskais līdzeklis Download PDF

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LV12177B
LV12177B LVP-98-126A LV980126A LV12177B LV 12177 B LV12177 B LV 12177B LV 980126 A LV980126 A LV 980126A LV 12177 B LV12177 B LV 12177B
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hjih
φβρομοηοβ
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LVP-98-126A
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LV12177A (lv
Inventor
Sergei Dmitrievich Burlakov
Dmitry Dmitrievich Genkin
Kirill Gennadievich Surkov
Viktor Veniaminovich Tets
Original Assignee
Sergei Dmitrievich Burlakov
Dmitry Dmitrievich Genkin
Kirill Gennadievich Surkov
Viktor Veniaminovich Tets
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Application filed by Sergei Dmitrievich Burlakov, Dmitry Dmitrievich Genkin, Kirill Gennadievich Surkov, Viktor Veniaminovich Tets filed Critical Sergei Dmitrievich Burlakov
Publication of LV12177A publication Critical patent/LV12177A/lv
Publication of LV12177B publication Critical patent/LV12177B/lv

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    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/44—Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Description

LV 12177 ΑΗΤΗΓπΚ)ΚΟΚΟΡΤΉΚΟΗ£ΗΟΕ JIEKAPCTBEHHOE CPE^CTBO. I Q6nacTb τζχηηκη. H3o6peTeHHe othochtch k mszchuhhc, KOHKpeTHO κ anTH-rnioKOKOpTHKOttaHfaiM npenapaTaM HecTepoHūHofi npHpojai, T.e.He coaepacaiujK b CBoeS xnMHHecxofi CTpyxType crepaHOBoro anpa, h npeaHa3HaHeHO jlth 3ainnTbi coμβτηηecxHx κπβτοκ MJieiconHTaioiuHX ct 5 neberam πιιοκοκορτΗχοστβροΗ,ζΐΗΗΧ γορμοηοβ. npeamecTBVKiuiHH vpoBeHb τζχηηχη. H3BecTHbi npHMeHaeMbie b MenniiHHS Bemecraa nonaBJisiomHe ΠΠ0Κ0Κ0ρΤΗΚ0Η2ΗγΚ> aKTHBHOCTbt
1. BemecTBa, noaaBJiaiomHe cnHTe3 cTepomiHbix γοόμοηοβ Ha pa3;iHHHbix to cTamixx (HHrHOHTopbi φβρΜβΗΤ0Β,κ3Τ3ΛΗ3Μρνί0ΐ[ΐΗΧ cnpenejieHHbie CraaHH CHHTsaa cTepomiHbix γορμοηοβ [l]): a) npon3BOziHb!e ūMcbcHHUMsraHa, HanpHMep, aMcpeHOH 5. noitaBOSiouiHH CHHTS3 CTepOHHHbIX ΓΟρΜΟΗΟΒ Ha ΟΤΟΙΙΗΗ ll-β - , I7 - Η 2I - THJipOKCHna3fa»; 6) npoH3BOHHbie nHpHaHHa (SU- c cepna), HanpHMep. Me-rapanoH, 15 nOHaBJDUOLUHH 0ΗΗΤδ3 Ha CTaūHH 1 1 β - rHūpOKCHira3bi: b) 3aMemeHHbie α,α. - rcnoTapaMHHbi, HanpHMep, aMHHonnoTeTHMHii, npemrrcTBViomHH CHHTe3y nperHeHOJioHa H3 xonecrepHHa, nonaBnss 20-a -rHnpoKCH na3y h C20, C-22-nHa3yt r) crepOHHHbie BeuiecrBa, 20 HanpHMep, TpunocraH (3β -3aMemeHHbiH crepoHj- 3β -rHnpoKcn-5- aHnpocreH-17-OH), nonaBJiaioiiiHH 3β- je3oxc;icTepomrft!iporeHa3y - 5.4 - H30Mepa3y [4ļ. 2. BetnecT3a,noaaBjiaiomHe ropMOH-peuenTopHce 33awmonežctbhe rJHOKCKOpTHKCHIHbiX ΓΟϋΜΟΗΟΒ [5]: 13 a) crepoHHHbie BeaiecrBa.
HanpHMep,MH(i)enpHCTOH (1 Ιβ - 3aMeuieHHoe CTepoanHoe npoH3BOHHoe-11β-{4 HHMerHJi -aMHHO(peHHJi)- Ι7β - ΓΗπροκοπ- 17 a-(npon-l-HHHJil)-3crpa-4,9 -ΛΗβΗ-3-ΟΗ), 00pa3yiOUiHM ' C peuenTOpOM rniOKOKOpTHKOHiXHbIX ΓΟΟΜΟΗΟΒ KOMnne.KC, HecnOCOOHblH 3anyCTHTb MexaHH3MbI ΠΠΟΚΟΚΟρΤΗΚΟΗϋΗΟΓΟ 3φφβΧΤ3 [3]; 6) HecTepoHūHbie BeuiecTBa [2], HanpHMep, npoTaBepHHa πυροχηορΗΐι ( npOH3BOJ[HOe H30XHH0JIHHa -1-(3,4 -HH3TOKCHD6H 3HJIHHeH)-6,7 - JIH3TOKCH-1,2,3,4—TerparHJtpoH30XHHOJiHH), hjih aueTHJicajiHUHJiOBaB KHaiOTa[5]. riepeHHCJīeHHbie JieicapcTBeHHbie cpencrBa aaiOT onpeaeneHHbiH ΒΗΤΗΠΠΟΚΟΚΟρΤΗΚΟHŪHblH ΒφφδΚΤ^,Ι^ΗΗ npHMeHHblMH B COCTaBe TOH HJIH HHOH JICKapCTBeHHOH φορΜΜ.
Pi3BecTHO TaKHce, hto BbimenepeHHCJieHHbie cpencrBa HMeioT paji cymscTBeHHbix HeaocraTKOB: 1. IIpenapaTbl, ΗΗΓΗ6κρ>ΤΟΙ11Ηβ CHHTS3 ΠΠΟΚΟΚΟρΤΗΚΟΗΛΟΒ, ΠΗΓΗΟΗρΥΙΟΤ B 3aBHCHMOCTH OT φβΌΜβΗΤΟΒ - ΜΗΙΗβΗβΗ TaiCKe CHHTS3 ηρΥΓΗΧ CTSpOHjIHbtX ΓΟΰΜΟΗΟΒ: nOJIOBbIX CrepOHIIOB Η/HJIH MHHepaJIOKOpTHKOHHOB, BbI3bIBaiOT HaxotiJieHHe npeiiiiiecTBeHHHKOB - cyocrpaTOB HHrn6HpyeMbix φβρΜβΗΤΟΒ. tbkhcs oojiaaaīoaiHX ropMOHajībHOH aKTHBHOCTbio.
2. IIpenapaTbi 2 rpvnnbi ημθιοτ oneHb HH3xyio ςπβΗΗφΗΗβοκνιο axTHBHOCTb, T.e. npoHBJiHiOT xax βητηπποκοκορτηκοηιιηυιο, Tax h jpyryio crepcHiiHyīO aHTHropMOHajIbHVIO a:<THBHOCTb. 3. Bce crepoHūHbie BeuiecTBa Tax hjih nnane HapvuiaioT oajiaHC crepoHnoB b opraHH3Me h noTSHUHajībHO MoryT oopaaoBbiBaTb h MeTaoojiHTbi, cojianaioiiiHe HHOH aKTHBHOCTbio, ΗΚΚβΠΗ CaMO ΒβΙΙΙβΟΤΒΟ,ΒΒΟϋΗΜΟβ Β OpraHH3M.
JleKapcTBeHHbiS npenapaT ΜΗφβπρΗοτοΗ (RU 486),conepxcauiHH crepoHHHoe jmpo. b HaHOOJibmefi crsneHH caočoneH ot YKa3aHHbix HeaocraTKOB , Hanoojiee οπειίΗφΗΗβπ b othoui8HHH ojiOKanbi ρευεπτοροΒ TJIIOKOKOpTHKOHHOB Η ΠΟ CBOHM φapMaKOJIOΓHHeCXHM 3φφβΚΤ3Μ Hančojiee ojih30k X 3aaBJiaeM0H rpvnne jiexapcr3eHHbix bsuisctb. Eojiee nonpcoHO oh onHcaH, HanpHMep. 3 [3] hjih [6]. Jļanee 3 3asBxe 3φφβχτΗΒΗθοπ> 3a3B.Tae.Moro cpencrBa mu 6υ;κμ cpaBHHBaTb,Hame acsro.c hhm. Hapanv c oojibuiHMH jocroHHCTBaMH. ΜπφβπρΗοτοΗ, xax h jpvrne aHanorH. HMeer pin cna6bix msct: - npenapar 3φφβχτΗΒβΗ nnuib 3 3bicoxHX ao3ax ( 400 μγ b zteab); - npenapaT conepJKHT 3 c3oen CTpyxrype CTepOHjiHce aapc: 3 LV 12177 - npenapaT CBH3biBaeTca Taiace c peuenTopaMH ποιιοβηχ CTeponnoB, nporeCTHHOB H MHHepaJIXOpTHKOHūOB. H3BecTHbi TaicKS φβροΜΟΗΒΐ HacsKOMbix - BemecTBa, Bbrpa6aTbiBaeMbie h BbineJineMbie OKpvxcaiouiyK) cpeny nacsKOMbiMH, HMeromHe οπειίΗφΗΜβοκΗΗ 3anax,B03ūeHCTByK)uiHH Ha οπβιΐΗφΗΗβοκΗβ (φβροΜΟΗΟΒωβ) peuenTopbi BOcnpHHMHHBbix ocoSen τογο xce BHjia, BbDbiBaa y hhx xapaKTspHyio noBeaeHHecKyw peaKUHio hjih npouecc, HanpHMep, npHBJieMeHHe κ MecTy CKomieHHa ocooeā npoTHBonojioHCHoro nona, πογοτοβχυ κ oruioflOTBopeHHio h ap-PJ. OūHa H3 rpynn φβροΜΟΗΟΒ npeflCTaBJiaeT co6oh,b ηβοτηοοτη, OTHHHOuenoHeHHbie aju^aTHHecxne HenpeflejibHbie αΐΗρτω, 3φκρω, aueTaTbi, coaepxcamHe b JiHHeftHofi yrneBoaopoziHofi lienu ot ĪO no 21 βτομοβ yr.iepona. ΦβροΜΟΗΗ naHHOH rpynnw Hcnojib3yiOT jum 6opb6w c HaceKOMbiMH -BpenHTeJIBMH CejIbCX0XO3HHCTBeHHbIX paCTeHHii H 6bITOBblMH HaceKOMbIMH [7,8].
OnpeneneaHbie φΗ3Ηκο-ΧΗΜΗΗβΰΧΗβ xapaxTepHCTHXH yxa3aHHbix φβρΟΜΟΗΟΒ H HX CHΗΤδΤΗΗβΟΧΗΧ aHaJIOrOB H npOH3BOflHbIX, B HaCTHOCTH, BbICOKaa ΓΗηρθφθ6ΗΟΟΓΒ ai^aTHHeCXOH ΛΠΗΗΗΟηβΠΟΗβΜΗΟΗ )ΤΠβρθΙΙΗΟΗ CTpyxTypbi, npmiaeT hm cnocoČHoerb Jienco pacrBOpaTbca b acnpax h BcrpanBaTbca b 6HonorHHecxHe MeMČpaHbi, Hapymas ηχ φΗ3ΗχθΜεχ3ΗΗΗβοχΗβ CBOHCTBa (aciuDcocTHOcrb, npoHHuaeMOCTb), hto no3BOJiaer npHMeHUTb hx b cocraBe κομπο3ηιιηη xuw ycnneHHfl 4pe3xoacHOH npoHHuaeMCCTH nocieaHHx [lOļ. yxa3aHHaa ΓΗηροφοόΗοοτΒ oo-bacHaer h Hcnonb3yeMbie b MennuHHe h 6μο.πογηη b Hacroainee Bpewa OHOJioranecKne CBOHcraa naHHoft rpynnbi φβροΜΟΗΟΒ φερΟΜΟΗΟΒΙ 1) AHECTE3HPYK)niA3 CnOCOEHOCTL,onpeaejiaiomaii ηχ πρΗΜβΗβΗΗβ b xanecTBe aHecreTHXOB [l l]; 2) CIIOCOEHOCTL· ΥΓΗΕΤΑΤΕ EAKTEPHH [12] η ΒΗΡΥΟΕΙ [13.14], hto no3BOJiaeT πρπΜβΗΛΤΒ ηχ b ΜβζΐΗΐΐΗΗβ η οηοιιογηη mm 3thx uenen; 3) CIIOCOEHOCTL· HHflVTJHPOBATL· JIH3HC 3PHTP0UHT0B [15], onpenensiomaa hx npHMeneHHe b KaMecrae HHnyxTopoB JiH3Hca ΒρΗτροηπτοΒ [15].
ΟπβΒΗΐΐΗΟ,ΗΤΟ onHcaHHbie Bbiine H3BecTHbie csoficTBa yxa3aHHofi rpvnnbi φβροΜΟΗΟΒ Η HX CHHT8THHeCXHX aHaJIOrOB H npOH3BOHHbIX, H cooTBeTCTByiouiHe hm xocMerHHecxHe, canbcxoxo3JiHCT3eHHbie h 0HCJiorH4ecxHe ΠρΗΜβΗβΗΗΗ Ηβ ΗΜεΚΓΓ ΗΗΧΒΧΟΓΟ ΟΤΗΟΠΙβΗΗΧ Κ ΠΠΟΧΟΧΟΰΤΗΧΟΗϋΗΟΗ čLKTHBHOCTH 4 (ποηροόκο 3το VTBep'/KaeHHe 6yner aoKaaaHO hhjks), ποβτομυ hh y xoro H3 H3B6CTHbix HaM cneuHanHCTOB HHKoraa He B03HHKano HHTepeca κ yKa3aHHbiM BeiuecTBaM c tomkh 3peH«a nojiyneHHJ! c hx noMomtio aHTHrJUOKOKOpTHKO HJIHoro 3φφεκτΒ. 5 PacKPbiTHe H3o6oeTeHHfl. 3anaHeā Hacroamero n3o6pereHHa aaiiHerca ycrpaHeHHe nepeHHcneHHbix Bbirne HenocraTKOB aHanoroB - βητηπποκοκορτηχοηιιοβ- h co3jxaHHe ηοβογο Jūiacca JiexapCTBeHHbIX BemeCTB, 3φφβΧΤΗΒΗΟ ΟΠβΙΙΗφΗΜβΟΚΗ nOflaBJUIiOUIHX 3φφβΚΤ ΠΠΟΚΟΚΟρΤΗΚΟΗΑΟΒ Η ΓφΗΓΟΖΙΗΜΧ flJIH ΛβΚΒρΟΤΒβΗΗΟΗ ΚΟρρβΧΠΗΗ 10 ιιικροκοΓο Kpyra naTOJioruHecxHX coctohhhh, o6jianaiouiHX hh3xoh TOXCHHHOCTbIO H BblCOKHM Τερ3ΠβΒΤΗΗβΟΧΗΜ HHHeKCOM. 3Ta 3aaaHa pemaerca Tew, hto b Kanecrae ΒΗΤΗΓίϋοχοκορτΗχοΗϋΗΟΓΟ cpencTBa πρΗΜβΗΒίοτ φβροΜΟΗ HacexoMbix HecrepoanHOH npHponbi (T.e. He conepacauiHH b caoeS XHMHHecxož crpyKrype crepaHOBoro $mpa ) hjih ero 15 chHTeTHhecxHh aHajior, npencTaBJiaiomHH codoh jihdo HenpeflejibHbiž zuiHHHOuenoHeHHbiH 3ϋΗφ3ΤΗΗεοχΗΗ cnHpT, JiHČo ajībjierau, JIHOO 3φπρ, coaepacamHe b JiHHeāHOH vrJieBoziopoaHOH uenH οτ 10 no 21 btomob vraepona.
Bbi6op ocHOBaH Ha pe3yjibTaTax HCcīeaoBaHHH, npoBeaeHHbix aBTopaMH aaHHoro H3o6perreHHH, ODHapyycHBUiHMH ηοβηθ OHOjiorHHecKHe caoHCTBa 20 Ha3BaHHbix coeztHHeHHS, b tom HHCjie - cnocooHccrb nouaBJieHHa peuerrrop-onocpejjoBaHHoro aeācTBHa nnoxoxopTHKonnoB Ha coMaTHHecxne κηβτχκ MJiexo nHTaiOIUHX. ŪMeHHO 3th CBoācTBa yxa3aHHbix coeaHHeHHŽ,HeH3BecTHbie asropaM H3 HOCTynHbJX HCTOHHHKOB ΗΗφορΜΕΙΙΗΗ, IĪ03BOJIHJIH peaJIH30BaTb nOCTaBJieHHyiO 25 3aaany.
KpoMe Toro, juia ycHJieH«a TepaneBTHHecxoro 3φφβχτα, b KanecTBe aHTHropMOHajībHoro JiexapcTBeHHoro cpeacTBa bo3moxcho npHMeHeHHe CMecu HeCXOJIbXHX φβρΟΜΟΗΟΒ Η/HJIH HX CMHT3THMeCKHX aHEjlOTOB, npH 3TOM BbiOOp yxa3aHHbix BeuiecTB juiji CMecu npoH3BOHHTca no npHHUHny cymecT3eHH0 30 pa3JIHHHOH ΓΗΛροφΟΟΗΟσΓΗ, ΠρΟΠΟρίΙΗΟΗΟΙΙΒΗΟΗ JJIHHe yrJieBOnopOHHOH uenH: pa3HHua hjihh vrJieBoaopojiHbix ueneii nojUKHa obrrb He MeHee πητη. B noncjiHeHHe κ cxa3aHHOMy„ajia ynpomeHHX npoH3BoncTBa :<cHKpeTHbix jiexapcTBeaHbix φορΜ bo3mojkho npHMeneHHe npoH3BcaHbix φβρΟΜΟΗΟΒ h/hjih hx CHHTeTHHecxHX aHanoroB.Bbi6paHHbix H3 Tex xce cooopajKSHHH. 5 LV 12177
HeicapcTBeHHaH (£opMa Ha ocnoBe φβροΜΟΗΟΒ HacexoMbix BKjnosaer b ceoa oaHojrea hjih 6ojies JiexapcTBeHHbix BemecTB, CMeuiaHHbix c amiporeHHOH boūoh, φΗ3ΗοποΓΗΗεεχΗ coBMecTHMbiM 6yφepHbIM pacTBopoM (iipyrHM φ3ρΜ3ΙΙβΒΤΜΜβΟΧΗ npHeMJIHMbIM HOCHTSJI6M) HJIH BKJHOHeHHblMH B MHxpoxancyjibi (HanpnMep, HcxycTBeHHbie jiHnmiHbie CTpyxTypbi - πηποοομη hjīh apyrHe φapmaueBTMHecxn npneMJieMbie hochtmh) h n3roTaBJiHBaerca b Bune Ta6jierox, xancyji, HHbexuHOHHbix pacTBOpoB, Ma3en h apyrwx JiexapcrBeHHbix φορΜ. 3aaBJieHHaii crpyxTypa jiexapcTBeHHoii φορΜΒΐ no3BOJuer nojiynaTb jiexapcTBeHHbie cpeacrBa οφφεχτΗΒΗΟ οπειίΗφΗΗεοχΗ nojtaBJiaioiUHe φyHXI^HK> rjnOKOKOpTHKOHJ[HbIX ρβαβΠΤΟρΟΒ,ΠρΗΓΟΛΗΗΧ JICXapCTBēHHOΗ ΚΟρρεχίΙΗΗ uinpoKoro xpyra naTOJiorHMecxHX coctohhhh. Βο3μοχηο(γγβ nojiyHeHHB 3aaBJiaeMoro nexapcxBeHHoro cpejicTBa HJunocrpHpyerca aieayiomHMH npaxTHHecxHMH npHMepaMH. ΠΡΗΜΕΡ l.Ha ocHOBe οληογο <ļwpoMOHa hjih ero cnHTCTHHecxoro aHanora. 500 ΜΓ ΛΗΠΗΛΟΒ ( ΛΗΠ3ϋΒΜΗΤΟΙ1Ιΐφθθφ3ΤΗίΙΙΙΙΙΧΟΛΗΗ, φθθφΒΤΗϋΗϋθερΗΗ B MOJiHpHOM OTHomeHHH 10:0,1) h 100 ΜΓ Z-l 1 - TerpaaeuHHona (HenpeaenbHbiS ΒΠΗφΒΤΗΗΒΟΧΗΗ CIlHpT C ΛΠΗΗΟΪί >ΤΠβΒΟί[θρθίΙΗΟΗ ΙίβΠΗ 14 H TpaHC-3B0HH0H CBB3bIO Btl nOJIOBCeHHH ) pacTBopjnoT B 500 MJI ΧποροφορΜΒ ΓφΗ 22° C H noMemaioT b TOiicrocTeHHyio xpyrnoaoHHyio xoji6y o6beMOM 4 jnnpa. Koji6y noMemaioT Ha. poTopHbifl ncnapHTejib h yflanaioT pacTBopHTejib npw 65° C. Ha crreHxax xoji6u o6pa30BbiBaerca TOHxaa nojiynpo3paHHaa ruieHxa. Kojičv noMemaioT b cyuiHJibHbiH ιιιχ3φ h nocyuiHBaiOT b BaxyyMe b τβΗβΗΗΗ 1 naca. B xoJi6y βηομτ 10 mji ziBaauu»! jiHCTHJiHpoBaHOH jieHOHH3HpoBaHOH BOiibi h noaie npozryBKH xoji6bi reaneM perHapHpyioT rmeHxy nyTeM hhtshchbhoio BCTpaxHBaHHJi npH 65° C b τεπεΗΗΗ 1 naca. 06pa3yerca 10 mji rycT9ro rejw c 3eneHOBaTbiM ott2hxom. Tejib pa3B0iWT 90 mji φοεφητΗΟΓΟ 6yφepa (pK 7,4; 22° C) H BCTpflXHBaiOT B Τ3ΗβΗΗΗ 30 ΜΗΗ>Τ npH 22° C. 06pa3yeTCX 100 MHJIHJIHTpOB cycne«3HH, xoTopyio o6pa6aTbiBaiOT yjibTpa3ByxoM npn 44 xTu 30 pa3 no 30 cexyHU c MHHVTHbiMH HHTSpBajiaMH. 06pa6oTaHHyio yjibTpa3ByxoM cycneH3HK> HBaxdb; noaiejioBaTejibHO nponaBJiHBajcT non jiaBJienneM a30Ta nepea noiiHKapooHaTHbie MeMČpaHbi c UHaMerpoM nop cnanana 500,h sanes 100 HaHOMsrpoB. 06pa3yerca onajiecuHpvromaa ycneH3nx, npeacrasjiHicujaa cočofi BOflHyro B3Becb wajieHbXHX ojiHoaiOHHbix JiHnocoM pa3MepoM 80-130 6 H3.HOMerpoB, conepxcamHX 500 μγ jimihuob h 100 μγ Ζ-(11)- TeTpaneiiHHOJia. 100 mji nojrvMeHHOH cycneH3HH nHcneprupvioT 3 120 mji HarpeToS no 80° C Ma3eBofi ochobbi, cocTOflmefi H3 BaneJiHHa, BocKa,cop0HTOJia TpHOJieaTa (30:2:5). IIoJiyHeHHbiH KpeM φacyΐoτ b Tyobi no 2 r, conepacaimie l μγ Z-l 1-5 TeTpaneueHOJia b 2 r JinnocoMajībHoro KpeMa. ΠΡΗΜΕΡ 2. Ha ocHOBe nsyx φβροΜΟΗΟΒ hjih hx cHHTerHHecKHX aHajioroB. 100 μγ Z-(9)-TerpafleueHmiaueraTa (HenpeneJibHbiii ΒΐΐΗφΒΤΗΗεοχΗίί 3φκρ c flJIHHOH yrneBOffOpOflHOH ΙΙβΠΗ 14 H TpaHC-nBOHHOH CBH3bKD B 9 ΠΟΠΟίΚβΗΗΗ) H 30 10 μγ Z-(l 1)- renTameuHHOJia (HenpenenbHbiH 3ΐΐΗφητΗ hecKHH οππρτ c ūjihhoh ueiiH 19 H TpaHC- ABOHHOH CBJI3bIO B 1 1 nOJIOJKCHHH ) paCTBOpBKJT B 500 MJI crepHJībHoro οιιηβκοβογο Macna. IIojiyHeHHbiH pacreop pa3jiHBaiOT no Φιιβκοηβμ c nocjieayioineH cTepHJimaimeii h repMenrcaiiHeH. nojiyaaioT jieKapcTBeHHyw φopMy1 totobjto juia napeHTepajībHoro (nonKoacHoro) 15 ΠρΗΜβΗβΗΗΒ. ΠΡΗΜΕΡ 3. Ha ocHOBe onHoro npoH3BOflHoro φβροΜΟΗΒ - (6eH3HJiOBoro 3φκρΒ a.i^aTHHecxoro HenpenejibHoro cnupTa (Z-(I4) renTaneuHHOJia) 500 μγ ΠΗΠΗΛΟΒ ( φocφaTHiIHJIXOJIHH, φθθφΒΤΗΙ[ΙΜ3ΤΒΗθηΒΜΗΗ, XOJieCTepHH B 20 MOJISpHOM COOTHOUieHHH 1:0,01:0,5) paCTBOpJIMT B 400 MJI HHSTHJIOBOrO 3φπρΒ npn TeMnepaType 22° C. 50 mji Z-( 14)-renTaneuHHHJi0eH3oaTa pacrsopsiOT b 1 mji HHMernjicyjn^oKCHna npn 60° C, 3aTeM oxjiaacaaioT no 22 °C h npiurasaiOT no KaiumM κ 400 MHJiHJiHTpaM pacrsopa jiHmmoB b hh3thjiobom 3φκρβ npa HHTeHCHBHOM nepeMeuiHBaHHH. K nojiyHeHHOMy b pe3yjibTaTe pacrBopy 25 JIOČaBJiaiOT 100 MJIJIBaacnbl nHCTHJIHpOBaHOH nSHOHH3HpOBaHOH BOHbl H o6pa30BaBiiiyioc5i nB)^a3Hyīo CHtrreMy o6pa6aTbiBaioT yjibTpa3ByxoM no HCMeaΗΟΒδΗΗίΐ rpaHHiibi paanena φ33 n nonyHeHHa nHcnepcrHon cHcreMbi (3Myjib«iH). OpraHHHecxyio φa3y ynajifliOT Ha ροτορΗΟΜ HcnapHTenenpH TeMnepaType, npeBbiuiaiouieH TeMnepaTypy φ330Β0Γ0 nepexoaa HaHcojiee 30 TyronJiaBKoro «3 npHcycTByiomHX b CMecn φοοφοιίΗΠΗϋΟΒ (60° C) πρκ nocreneHHOM yc;uieHHH BaxyyMa no 0, l τορ (κ κοπυγ ynapHBaHiw). 06pa3yerca 100 mji rvcToro rejia, κοτορωπ nocne 3aMopaacHBaHHH b hchidcom a3CTe noiiBepraiOT JIHcφHHbHOMy BbicyuiHBaHHio. Očpaaverca ποροιηοκ coineii MaccoH 550 μγ. Ποροιιιοκ npeccyioT b TaojiencH, conepacaume 50 MraHimna h 5 35 MrZ-(14)-rsirraneuHHHJi6eH3oaTa, jihčo ynaKOBbiBaioT bo φι^οπω LV 12177 coaep'/Kamne 50 μγ Jinnuna h 5 μγ Z-(l4)-renTaaeuHHHJiauerajiji. nojiyHaercfl JieKapcTBeHHaji φορΜΒ, roTOBaa juia nepopajībHoro, napeHTepaiibHoro hjih HHTpaHa3anbHoro npHewa.. ABTOpaMH OnpOOOBaHbl OOJIblIIHHCTBO H3BSCTHbIX φερΟΜΟΗΟΒ yxa3aHHOH 5 rpynnbi hjih hx CHHTeTHHecxHX aHajioroB auž onpeaejieHHa HajiHHHB y hhx aHTHrjnoKOKopTHKOHiiHoro neficTBHJi Ha coMaTHHecKHe ιαιετκΗ MJieKonHTaiouiHX. OKa3ajiocb, hto 3Ta cnocooHocrb b toh hjih hhoh CTeneHH npHcyma bcsm hm. KoHKpeTHbiH BbiSop φεροΜΟΗΒ onpeflejiHercs HOCTynHOCTbK> φβρΟΜΟΗΟΒ, HX CnOCOSHOCTblO K B3aHMOHeHCTBHIO C 10 HOCHTeJMMH.npOHHUaeMOCTblO B SHOJIOrHHeCKHe CTpyKTypbI, ΒρβΜβΗβΜ ΧρΕΗβΗΗΗ ΓΟΤΟΒΒΙΧ φορΜ,ΤΟΚεΗΗΗΟεη,ΙΟ Η flpyTHMH ΓφΗΗΗΗΒΜΗ, HenpHHUHIIHajIbHblMH C ΤΟΗΚΗ 3peHRH 3ΒΒΒΠβΗΗΟΓΟ ΗΒΜΗ aHTHrOpMOHaJIbHOrO 3φφεΚΤΒ. ΟπβΒΗϋΗΟ,ΗΤΟ JDIΛ 3φφβΚΤΗΒΗΟΓΟ JieHeHHH KOHKpeTHbIX ΒΗΛΟΒ HapyiHCHHH B03M0XCeH Bbl6op φβρΟΜΟΗΟΒ JiaHHOH rpynnbl B CaMblX pa3HbIX 15 co«iexaHHHx. Hto xacaerca Bbičopa coHeraHHŽ φερΟΜΟΗΟΒ hjih hx CHHT8THH6CXHX aHaJIOrOB, TO OH OnpeaeJieH pa3JIHHHOH ΓΗΛρθφθ6ΗΟΟΠ»Κ> cocraBJMioiUHX, hto o6yciaBJiHBaer hx pa3JiHHHyio 0HojiocTynHOCTb juki pa3JiHHHbix TKaHea h opraHOB.HanpHMep, b ποηχη ;iyHme npoHHKaiOT MeHes ΓΗΐιροφοοΗωβ BemecrBa,a b neneHb η μο3γ - oojiee ΓΗΛροφοοΗωβ. 20 npoMbimjieHHaa nPHMeHHMOCTb. B npHJiaraeMbix TaojiHiiax 1,2,3 npHBeaenbi pe3ynbTaTbi cpaBHHTejibHbix HcnfaiTaHHH 3ajiBJieHHoro JiexapcTBeHHoro cpencTBa c aHajioraMH h KOHTpOJIbHOH rpvnnOH.
Ta6jIHUa 1 - 3φφβΚΤΗΒΗ0ση> npHMBHCHHJI 33ϋΒΠ6ΗΗΟΓΟ jieKapcTBenoro 25 cpeacTBa πρκ pa3JiHHHofl MoaejiHpyeMOH coMaTHHecxoH naTOJiorHH, BbOblBaeMOii H36bITOHHbIM 3φφβΚΤ0Μ ΓΛΙΟΚΟΚΟρτΗΧΟΗΙΙΗΒΙΧ ΓΟρΜΟΗΟΒ.
Ta6jiHua 2 - 3φφεκτΗΒΗθθΐ^ πρπΜβΗβΗΗΛ 3aaBJieHHoro nexapcTBeHoro CpejICTBa npH pa3BHTHH HHiiyUHpOBaHOH rJHOKOKODTHKOCTepOHJtaMH 3ΤρθφΗΗ kohch (noaaBJieHHe Bbi3BaHHoro 6eTaMeTa30H0M HcroHHeHHH kojkh) 30 TaSjiHiia 3 - aHTHrTiOKOKopTHKOHjiHaH (aHTHKaTačojiHHSCKan) aKTHBHOCTb 3ajiBJieHHoro JieKapcTBeHoro cpeacTBa apH MOnejiHpOBaHHH H3HypHK3IHHX φΗ3ΗΗε0ΧΗΧ Harpy30K (nJiaBaHHe B 0aCC3HHe).
H3 TaČJiHii 1 h 2 cneayeT,‘rro 3a*BJieHHoe cpejcrBO HMeer 6cjies ιιΐΗροκνκι O^JiaCTb 3φφβΚΤΗΒΗΟΓΟ ΠρΗΜβΗεΗΗΧ ΙφΗ naTOJIOrHHeCXHX COMaTHHeCXHX 35 np0ueccax, CB5I3aHHbIX C TSHCTBHSM nHOKOKOpTHXCCTepOHIIOB H 8 UHTOTOKCHMeCXHX φαΧΤΟρΟΒ, ΓφΗΗβΜ ero 3φφεκΤΜΒΗΟ<ΓΓΒ 3HaHHTeJIbHO Bbuue,HeM y aHanoroB h αΐΗροκο npnMeHaeMbix npenapaTOB. H3 TaojiHUbi 3 αιβΛγβτ,ΜΤΟ 3aaBJieHHoe cpeacTBo 3HanHTenbHO 3φφδκτΗΒΗβζ aHajiora npenaTCTByeT pa3BHTvno KaTaoo:iHHecKHX (onocpeaoBaHHbix raiOKOKopTHKOHiiaMH) Η3ΜβΗβΗΗΗ b opraHH3Me ripu UeHCTBHH HHTSHCHBHbIX φΗ3ΗΜβΟΧΗΧ Harpy30K.
TaSjiHua 1. 3φφεκτΗΒΗ00ΓΒ πρΗΜβπεΗΗΛ 3aaBJueMoro JieKapcTBeHHoro cpeacTBa fipH pa3JIMHHOH ΜΟΛΜΗργβΜΟΗ COMaTHMeCKOH ΠΒΤΟΛΟΓΗΗ, BbI3bIBaeMOH H30bIT0HHbIM 3φφβΚΤΟΜ ΠΠΟΚΟΚΟρΤΗΚΟΗβΗΒΙΧ ΓΟρΜΟΗΟΒ.
Moaeab coMaTHHecKOH naTOJiorHH. JIexapcTBeHHoe cpe^CTBO, cxewa BBeneHHa, no3bi. IIoKa3aTejiH 3φφβΚΤ3. 1 2 3 0*HpeHHe CB5J3aHHOC H36bITKOM πποκοκο-pTHKOHHOB y Kpbic JĪHHHH Zucker TopMOJKeHHe npHoaBKH b Bece Ha 20 aeHb;% 3aaBJweMoe JieKapcTBSHHoe cpejicTBO, 10Mr/xr,e«eziHeBHO OBHOKpaTHO ΠΟϋΚΟ>ΚΗΟ 88% ΜπφεπρΗστοΗ, 10Mr/Kr,8ace-AHeBHO OflHOKpaTHO nOHXOXCHO ( npHMeO Π 53% KOHTPOJIb 0% H3Ba xcejiyaxa Bbi3BaHHaa annjraxauHeS na cjiH3Hcryio οβοποΗκγ xcenyinca 100% yxcvcHOH κηοιοτη c nocjienyiomHM eacezmeBHbiM BBeneHHeM 2,5μγ\κγ rnap0K0pTH30Ha; Kpbicbi Wistar OTMena 3anep2CKH 3a»HBaeHHJiio, BbJ3BaHHOH XpOHHHeCXHM BBexceHHe>i nuipOK0pTH3OHa;% 14ūeHb 3aHBJiaeMoe jieKapcrBeHHoe cpeacTBO,5Mr\KT ,3 pa3a b aeHb b.m. β τβπβΗΗΗ ! 4 HHefi (ΠρΗΜευΙ) 87 ΜΗφεΠρΗΟΤΟΗ, 20 ΜΓ’-ΚΓ ,3 paaa b aeHb b.m. β τε^επΗΜ 14 £Hefi 45 IiMMerntnMH* 20 μγ\κγ 3 pa3a B aeHb B.M. B TSHeHHH 14 BHefl 15 ! KoHTDoab 0 * Ι^ΗΜβτΗΛΗΗ Β3ίΐτ β xanecTBe jonojiHHTenbHoro npenapara cpaBHemw , oojiaaaioinero npvrHMH (He CBjmHHbiMH c βητηγπμκοκορτηκοηηβιμ 3φφεκτοΜ) .vtexaHH3MaMH neiicTBHJi , ho aBJunomercca ohhhm H3 HaHOoaes πρΗΜεπκβΜωχ a HacroHUies Bpe.vui jjia jieneHHB aaHHon narorcontH. 9 LV 12177 npoiiojiaceHHe Ta6nHUbi l.
SKcnepHMeHTanbHbiH ΗΗφ3ρΚΤ MHOKapaa, 6ecnopoflHbie Kpbicbi CHHaceHHe pa3MepOB 30HbI Hexpo3a;% l CVTKH 7 C7TKH KOHTPOJIb 0 0 3aaBJweMoe jrexapcTBeHHoe cpeacTBo 10 μγ/κγ OflHOKpaTHO b/m (TIpHMep 3) 68 89 ΜΗφβπρποτοΗ (RU486) 20 μγ/κγ ozcHOKpaTHo b/m 17 28 HHTporJIHUepHH1 OZtHOKpaTHO b/b. 30 55 *HHTponiHuepHH B3ST b Kanecrae jtonojiHHTenbHoro apenapaTa cpaBHenHa , o6jiaflaiOmerO flpjTHMH ( He CBJI3aHHbIMH C aHTHrJIIOKOKOpTHKOHHblM 3φφβΚΤΟΜ) MexaHH3MaMH neHCTBHa , ho HEJiaioiueroca ohhhm H3 Hancojiee npHMeHaeMbix b Hacroames Bpevta fljia JieneHHS jiaHHOii naTOJiorHH. nponojDKeHHe TaS^HUbi l.
Hhbojuolihb THMyca, Bbi3BaHHaa TpaBMOH y 6ecnoponHbix Kpbic. noitaaneHHe hhbojuouhh % Macca <3ΤΦ1 KoHTpOJIb (HHTaKTHbie acHBOTHbie) 0 0 3aaBJWMoe jieKapcrBeHHoe cpencrBO,5Mr/xr, 3 pa3a b aeHb b/m b TeneHHH 5 aHež nocjie TpaBMaTH3auHH 70 57 ΜΗφβπρποτοΗ, 20 μγ/κγ , 3 pa3a b aeHb b/m b τεπβΗΗΗ 5 ϋΗβΗ noaie TpaBMaTH3aUHH 25 17 JIeBaMH30Ji2 , 10 μγ/κγ , 3 pa3a b aeHb β/μ β tshshhh 5 ΖΙΗβΗ nocie TpaBMaTH3ailHH 5 20 1
KoHueHTpauHJi cbiBopoTOMHoro THMHHecxoro φaκτopa 2 JIeBaMH3on Β35ΓΓ b Kanecrse jononHHTejibHoro npenapaTa cpaBHSHM , o6jiaaaioiuero jrpyrHMH ( He οβ#3βηημμη c βητηπποκοκορτηχοηηβιμ ΒφφβχτοΜ) MexaHH3MaMH aeācTBHJi, ho ABJiaioiueroca ohhhm H3 Hancojiee npHMeHaeMbtx 3 HacTOHUiee BpeMa iuis Jienenna aaHHofl naTOJiorHH. 10
TaojiHua 2. 3φφβκτΗΒΗ0<π^ npHMeHeHHa 3aaBJiseMoro nexapcTBeHHoro cpencrBa npw pa3BHTHH HHjiyunpoBaHHOH nnoKOKopTHXocTeponnaMH ατροφΗΗ ΧΟΪΚΗ (noņaBJieHHe BbOBaHHoro oeraMeTaaoHOM** HCTOHHeHHa (atpodīHH) kohch ;%) npenapaT,cxeMa BBeneHHk„no3bi* *** IlojiaBneHHe Bbi3BaHHoro 6erraMeTa30HOM** HcroHHeHHa ΑτροφΗΗ) ΧΟΪΚΗ ;% KOHTpOJIb o MHienpHCTOH (RU486) 1,5 hM/cm.kb. 7 3aaBJweMoe nexapcTBeHHOe cpencrBO, 0.5hM/cm.kb (TIpHMep 2) 87 1.25-nHnmpoKCHBHTaMHH D3**** ,1 nM Ha cm2 65 * IIpenapaTfai BBonnjiHCb eHcenHeBHO b τβΗβΗΗΗ 10 nHefi Ha φοΗβ BBeneHH* 6eTaMeTa30Ha **BeraMeTa30H β τβπβΗΗΗ 10 ληθη no 2,5 hM Ha kb.cm. eaceaHeBHO ***MbiuiH C3H ,8-10 MbimeS b rpynne **** 1,25-nHrHapOKCHBHTaMHH D3 β3λτ β κΒΗβοτΒβ nonojiHHTejibHoro npenapaTa cpaBHeHĪia , o6jianaiouiero npyrHMH (He CBjnaHHbiMH c βητηπιιοκοκορτη- KOHHHblM ΒφφβΚΤΟΜ) ΜδΧΒΗΗ3Μ3ΜΗ HeHCTBRS , HO HBJIHKDIHerOCJI OflHHM H3
Han5ojiee ynoTpe6HTeJibHbix b Hacrojimee ΒρβΜΛ απχ ηβπβΗΗΛ ζιβηηοη naTOJiorHH.
Ta6;iHua 3. Αητηπποκοκορτηχοηιιημ (aHTHxaTa6ojiHHecxax) βκτηβηοοτβ 3aaBJieHHoro neKapcTBenoro cpencTBa npH MonenHpoBaHHH H3Hyp5«oinHx AH3HMecxHX Harpy3QK (njiaBaHHe b oacceHHe)._ JIexapcTBeHHoe cpeacTBO, £03 bt, pe>KH M BBeneHHH. H3MeneHHe MbimeHHOH Maccbi; % Ha7 neHb Η3ΜβΗβΗΗΗβ aXTHBHOCTb ΜΗΟφΗβρίυίΠΗρ-hoh npoTea3bi**;% Ha 7 neHb H3MBHCHHC aKTHB- hocth πηοκοκσρτΗ-xoHjiHbix peuenTo-pOB B JieHKOUHT-ax*** ; % Ha7 neHb HHTaKTHbie aCHBOTHbie 0 0 0 KOHTpOJIb -10 +20 +35 3axBnxeMoe Jie- xapcTBeHHoe cpencTBO, 10 μγ/χγ nep-opajībHO nepe3 5 MHHyT nocne npexpameHHJi Harpy3XH +20 0 0 ΜΗφεπρΗΟΤΟΗ (RU486) 20 μγ/κγ nep-opanbHO nepea 5 MHHyT nocne npexpameniM Haroy3XH +5 +7 +20 •BecnopoflHbje KpbiCbi,6-8 ικηβοτηβιχ b rpvnne. ** OnHH H3 BajKHeHiiiHX 6HoxHMHHecxnx noKaaaTeneii xara6o;iHHecxoro neScTBHii ΓηιοκοκορτΗκοΗηοΒ Ha μηοιιητβι. *** yxa3biBaer Ha crsnenb aKTHBHocTH ropMOH-penenTopHoro B3aHMoneHCTBHa h bjihshhh ropMOHa na xnerxy - MHUieHb.
II LV 12177
KpOMe ueneBbix 3XcnepHMeHTOB, b npouecce nccjieziOBaHHH ποοτοαηηο KOHTpcumpoBajiocb HanHHHe ποοοηημχ h tokchhcckhx ΒφφεκτοΒ - pa3flpa»eHHH KO/KH,CJIH3HCTbiX OOOJIOMeK.paCCTpOHCTBa nHmeBapHTenbHOH,CepfleMHO-COCVHHCTOH H HepBHOH CHCTSM, aJUieprHHeCXHX peaKUHH H T. Π. 5 TepaneBTHHecxHS Hnaexc cocraBHJi jum 3aasjMeMoro cpencrsa 100-300, hto 3Ha4HTenbHO uiHpe TepaneBTHnecKoro HH^eKca ΜΗφβπρΜΟτΟΗα (RU486). ΜοΗΗΤΟρΗΗΓ ypOBHJI nOJIOBbIX CTepOHflOB H MHHepaJlOKOpTHKOHHOB B KpOBH OflbITHbIX JKHBOTHbiX Ηβ BbMBHJI H3MeHSHHH npH ΓφΗΜβΗβΗΗΗ 3aBBJMeMOrO cpencrBa. 10 ΓΙο HameMy MHeHHio,3aaBJieHHoe jiexapcTBeHHoe cpeacTBO cooTBercTByer BCSM ΙφΗΤδρΗΛΜ naT6HTOCnOCo6HOCTH : OHO aBJMeTCB HOBbIM ( H3 flOCTynHbtX HaM HCTOHHHKOB ΗβΗ3ΒβΟΤΗΟ ΓφΗΜβΗβΗΗβ φβρΟΜΟΗΟΒ HaCeXOMbIX B KaHeCTBC aHTHropMOHaJībHoro cpejiCTBa), npOMbiuuieHHo πρΗΜβΗΗΜο (hto y6e;mTenbHo noKa3braaioT npHBejieHHbie b npHMepax h Ta6jniuax pe3yjibTaTbi) h HMeer 13 H3o6peraTenbCXHM ypoBenb, T.e. ΗβοπβΒΗϋΗο jijm cneuHajiHcra. IIoaieaHee yTBepacaeHHe mo>kho očocHOBaTb caeayioiuHMH λοβοαβμη: 1) HaCXOJIbXO aBTOpaM Η3ΒβΟΤΗΟ, HH ΟΛΚΗ H3 H3BeCTHbIX HeCTepOH2HblX πποκοχορτΗΧΟΗΛΗωχ npenapaTOB He yrHeTaer 6axrepHH h BHpycbi h ae HHjiyunpyeT jiH3Hca 3ρΗτρουπτοΒ 3a cneT caoero βητηγπιοκοχορτηκοηληογο 20 aeHCTBHH,T.e.flo HacToamero apeMeHH HeH3BecrHa cbhgo aHTHKopTHKommoro 3φφβχτ3 c yxa3aHHbiMH Bbmie (b pa3j;ejie ypoBeHb τθχηηχη) 6HOJiorHHecxHMH CBOHCTBaMH φβρΟΜΟΗΟΒ. 2) yxa3aHHbie b pa3fl«ie "ypoBeHb tsxhhkh" 6HOJiornHecxne CBOHCTBa aaHHOH rpynnbi φβρΟΜΟΗΟΒ (yrHereHne 6axTepHH,BHpycoB,HaayuHpoBaHHe JiH3Hca 25 apHTpoiiHTOB) npoaBJMioTca τολβχο b xoHueHTpauHax Ha Hecxojibxo nopajixoB Bbuue, hcm (xax αιβιιγβτ H3 pe3ynbTaTOB προΒβρχΗ, npHBeneHHbix b Ta6jiHuax) npoaBJMerca hx rjrroxoxopTHxoH,nHoeaeScTBHe,HTO c πο3ηιιηη K-iaccHHecxoH 3HHOXpHHOJIOniH BBJMeTCH OZIHHM H3 ΠΟΧΕ33ΤβπβΗ ΗβςΠβΗΗφΗΗΗΟΟΤΗ 3ΤΗΧ CBOHCTB (T.e.nOJiaBneHHB, HRHyKUHH). 30 3to aonojiHHTeabHO _aoxa3biBaer,HTO panes H3BecTHbie CBOHCTBa φβρΟΜΟΗΟΒ Ηβ HMeiOT ΟΤΗΟΙΙΙβΗΗΛ X aHTHrJIK)XOXOpTHXOHJIHOMy JCeHCTBHK). 3) H3BecTHO,HTO hh BHpycbi.HH 6axTepHH Ηβ ΗΜβιοτ peuenTopOB x r:iiOKOxopTHKOHaa,M, He 0ΗΗΤβ3Ηρνιοτ hx h nosTOMv ne oojiaaaioT τοηχβμη npHJTOaceHHil aeŽCTBHS HH r.HOXOXOpTHKOHHHblX ΓΟΟΜΟΗΟΒ, HH, ΟΟΟΤ3βΧΟΓΒβΗΗΟ, 35 aHTHnnOKOKOpTHKOHaOB.

Claims (4)

  1. LV 12177 IZGUDROJUMA FORMULA 1. Kukaiņu feromona, pēc būtības nesteroīda savienojuma vai tā atvasinājuma, vai tā sintētiskā analoga, kas attiecas uz nepiesātinātiem alifātiskajiem spirtiem, aldehīdiem vai esteriem ar alifātiskā ogļūdeņraža lineārās virknes garumu, kas satur 10-21 oglekļa atomus, pielietojums par antiglikokortikoīdu līdzekli.
  2. 2. Antiglikokortikoīdu līdzeklis, kas atšķiras ar to, ka šis līdzeklis satur efektīvu daudzumu kukaiņu feromona, kas pēc būtības atbilst nesteroīdam savienojumam, vai tā atvasinājuma, vai to sintētiskus analogus.
  3. 3. Līdzeklis saskaņā ar 2. punktu, kas atšķiras ar to, ka šis līdzeklis satur kukaiņu divu vai vairāku feromonu, kas pēc būtības atbilst nesteroīdam savienojumam, un/vai to atvasinājumu, un/vai sintētisku analogu, maisījumu.
  4. 4. Līdzeklis saskaņā ar 3. punktu, kas atšķiras ar to, ka alifātisko lineāro virkņu oglekļa atomu skaitļu starpība savienojumos, kuri ietilpst maisījumā, ir ne mazāka par 5.
LVP-98-126A 1996-01-31 1998-05-28 Antiglikokortikoīdu dabas ārstnieciskais līdzeklis LV12177B (lv)

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PCT/RU1996/000028 WO1997027845A1 (fr) 1996-01-31 1996-02-01 Medicament a base d'anti-glucocorticoide

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