LV10393B - Physiologically acceptable human protein medicament - Google Patents

Description

LV 10393

CoBMecTHMbiii npenapaT nejiOBe^ecKoro npoTeima

Oiracamie ΠρβΛΜβτοΜ HacTomiiero H3o6peTemtH hbjihiotch cTa6njibHbie, HeHMMyHOreHHbie, φΗ3ΗΟΛΟΠΓίβΟΚΗ XOpOIIIO COBMeCTHMbie, paCTBOpeHHbie HJIH Cy6jHMaUHOHHbie BbICymeHHbie rajieHOBbie Κ0ΜΠ03ΗΙΙΗΗ H3

UeJIOBeHeCKHX ΠρΟΤβΗΗΟΒ /ČeJIKOB/, B OCo6eHHOCTH 9pHTpOHOK3THH.

HejioBeuecKHe προτβΗΗΜ npe^cTaBjmioT cočoh ajrroreHHbie, HMeKDIIļHeCH TOJIbKO B He3HaHHTejIbHbIX KOJBTieCTBaX ΠρΟΤβΗΗΒΙ, KaK, HanpHMep, TKaHeBbift ruia3MoreHHbiH aKTHBaiop /t-PA/, cTpeirroKHHa3a, ypoKHHa3a, ΗΗτερφεροΗ, CTHMyJiHpy ioiuhb pa3juran>ie kojiohkh, φ3κτορΗ /CSF/hjih apHTpoHOHSTHH /EPO/. Ha npHMepe EPO; κοτορκΗ npe/inouTHTejibHO Hcnojib3yeTCH b cocTaBe , Η3θ6ρβτεΗΗβ noacHHeTCH ΠΟΛροόΗββ. 3pHTpOHOH3THH /EPO/ΠρβΛΟ^ΒΛΗβΤ Co6ofi ΓΛΗΚΟΠρΟΤβΗΗ, KOTOpbIH CTHMyjinpyeT o6pa30BaHHe reMorjioČHHa, cooTBeTCTBeHHO, apHTpouHTOB b kocthom M03ry. 3τοτ ΛΗΗοπροτεΗΗ o6pa3yeTCH rjiaBHbiM o6pa30M b nouKax, B -OHēHb He3HaqHTejIbHbIX KOJIHHeCTBaX HaXOflHTCH B CbIBOpOTKe H npn φΗ3ΗΟΛΟΠΡίβαΚΗΧ yCJIOBHflX HaCTHHHO BblAe^HeTCH B MOHe.

OxcyTCTBHe EPO IipH IIOUBHHOH HeflOCTaTOHHOCTH 00yCJI0BJieH0 peHajībHoft aHeMHeft. Bjiaro^apa bbsa^hhio EPO β φΗ3κο./ιοπίΗεεκΗχ KOJIKWeCTBaX, T.e. H8CKOJIbKO MHKpOīpaMM, 3a Omy HJIH HeCKOJIbKO A03Hp0B0K MOMCHO CHOBa B030y)KflaTb Β ΤΒΚΚΧ CJiyuaHX 00pa30BaHHe spHTpoiļHTOB. TaK Kan opraHH3M uyBCTBHTejibHo pearapyeT yxce Ha He3HaHHTe^bHbie H3MeHeHHH A03H, TO fl03HpOBKa AOJDKHa 6bITb TOHHO BOCnpOH3BO^HMa. 06bIHHO EPO HHbeKUHpyiOT HJIH BHyTpHMbIIIieUHO HJIH BHyTpHBeHHO b BHfle βοληογο pacTBopa hjih ββολητ b BHAe pacribiJiHeMoro pacTBopa uepe3 cjiH3HCTyio o6ojioHKy Hoca. Οαηβκο, H3BecTH0, hto EPO, η ΗΜβΗΗΟ KaK πρείΚΑε Bcero nojiyHeHHbiH H3 HēJiOBenecKOH mohh προΑγκτ /Miyake η Ap. J Biol. Chem. t.25, 5558 - 5564/, KaK Taoece nojiyHaeMbiii Me»yiy TeM nyreM tbhhoh HHHceHepHH npoayKTbi /BOHC 85 - 02610/, b boahom pacTBope HecTaČHjībHbi h ffSūKe npu xpaH6HHH npn - 80°C HacTynaioT čojibiirne ποτερκ aKTHBHocTH. 3th o6a Bima npoAyicTOB ounnaioTCH HeCKOJIbKO no o6pa3y rJIHKOJIH3HpOBaHHH Η ΠΟ aKTHBHOCTH, IIpHMOe CpāBHeHHe C CO^epMCaiItHMCH B CbIBOpOTKe EPO ao CHX nop HeH3BeCTHO. 3th ποτερκ aKTHBHocTH cbojihtch, c oahoh cTopOHbi, κ pa3pymeHHio EPO 3a c*ieT KaiajiHTHHecKHX οφφεκτοΒ ποΒερχκοοτΗ cjiyHcaiiiHX xpaHeHHH aMnyji 6jiaro^apa c/ieAaM Taxceju>ix MeTajuioB, KHCJiopoAy B03Ayxa Η T.A., C Apyrofi CTOpOHbl, OAHaKO, TaKHCe 3a CHēT OTJIOHCeHHH EPO -MOJieKyji Ha CTeHKax cocyAa, npHueM TaioKe momcct npoHcxoAHTb nacTHHHO AeHaTypauna. TaK KaK, KaK CKa3aHO Bbirne, b k3jkaoh ao3hpobohhoh eflHHHIļe AOJIHCHbl COAepHCaTbC^ TOJIbKO HeCKOJIbKO MHKporpaMMOB, nOTēpH 3a cneT aAcop6u;HH yxce cnycTH κοροτκοβ BpeMH xpaHeHHH MoryT 6biTb 3HaHHTeJIbHbIMH.

B eBponeiicKOM naieirre A - 178 576 no3TOMy onHcaHO ηηγη6ηροββηη6 3τογο OTJio^ceHHH Ha cTeHKax cocyAa 6jiaroAapa Ao6aBKe nojiHMepHbix COeAHHeHHŪ, KaK aJIb6yMHH CbIBOpOTKH HejlOBeKa hjīh KpynHoro poraToro CKOTa, JieiļHTHH, AGKCTpaH, IļejL/imcm, nOJIHSTHJieHIVIHKOJIb H T.A·, H TaKHM o6pa30M AocTHHceHHe cnycra npHMepHO 2 naca xpaHeHHH npH 20°C o0Hapy>KeHHH EPO b KOJiHHecTBe 75 - 98 %, b npoTHBonojioHCHocrb neMy 00HapyjKHBai0T tojibko 16% 6e3 TaKoS Ao6aBKH. Πρκ stom, ΒπροηβΜ, H3Mepajiocb TOJibKo o0Hapy*eHHe paAHoaKTHBHOH MapKepoBKH /^C/, TaK HTO 3TH OnblTbl ΗΗΗβΓΟ He IOBOpHT 0 CTa6HJIH3aiIHH EPO OT pa3JI05KeHHiI. 3aHBHTejieM yciaHOBJieHO, hto CTa6HJiH3aitHH b TeneHHe αλητθλβηογο BpeMeHH c noMonibio TaKHX cpe^cTB, OAHano, Hejib3H AOCTHraTb, T.e. EPO -aKTHBHocTb b TecTe Ha μβιπιη CHjrbHo naAaeT, κ TOMy Mce 3th cpeACTBa npH ΗΗφβΚΙίΗΗ BbI3bIBaiOT ΗΜΜφΉΟΓβΗΗΜβ peaKHHH. ΡΪ3 eBponeiicKoro naTema A - 178 665, Aajiee, n3BecTHbi "cTa6HJiH3aT0pbi", b oco6eHHocra jļjin cy6jmMannoHHO BbicyuieHHbix EPO -npenapaTOB. HapHAy c nojiHMepHbiMH BemecTBaMH Π3Γ 4000, jKejraraHOH h AeKCTpaHOM 40 Ha3BaHbi pa3JiHHHbie caxapa h MHoro3HaHHbie cimpTbi, Aaiomne npH οκηολθηηη MOHocaxapnAbi: βμηηοκηο,τιοτμ : HeopraHHHecKHe COJIH H THOJIbHbie COeAHHeHHfl. K0M6HHau;HH 3ΤΗΧ BemeCTB C HeJIOBeHeCKHM CbIBOpOTOHHbIM aJIb6yMHHOM, JKeJiaTHHOH H fleKCTpaHOM TaKHce yKa3aHbi. TanjKe b 3tom jiHTepaiypHOM ηοτοηηηκθ onpeaeAHeTCH o6HapyHcemie paAHoaKTHBHOCTeii τολβκο cnycTH 2 Mecaua xpaHeHHH cy6jiHMan;HOHHbix BbicymeHHbrx npoAyKTOB. Oho yKa3hiBaeTCH paBHMM 87 - 99%, b npOTHBOnOJIOJKHOCTb 60% 6e 3 Ao6aBOK. TaK KaK ./ΙΗθφΗ.7ΙΗ3ΗρθΒ3ΗΗΜΗ MaTepnaji HcnoAb3yeTCH HenocpeACTBeHHO nocjie nojiyHeHHH b KanecTBe CTaH^apTa, to He yKa3aH0, KaKHe eme ποτβρκ βκτηβηοοτη npH īipuroTOBJieHHH npenapaTOB. Tanace sth npenapaTbi otfjiaAaioT bmcokoh noTepeii ηκτηβηοοτη b TecTe Ha Mbmiax.

Ilo3TOMy 6biaa nocTaBJieHa 3aAana co3AaHHn χοροπιο οοβμθοτημογο EPO - npenapaTa, κοτορΒίίί CTačnjieH npn xpaHeHHH. T.e. coxpaHaeT in vivo aKTHBHocTb, He npHBOAHT κ aAcop6nHHM Ha CTeHKax aMnyji hjih nmpHiiOB h JierKO MOHceT nepeBOAHTbcn b HHbeKii;HpyeMyio φopMy.

HeoncHAaHHO 3Ta 3aAana pemaeTcn 6jiaroAapa noApo0Hee oxapaKTepH30BaHHOH b φopMyΛe H3o6peTeHHH κομ6ηηβηηη pa3JiHHHbix KOMnoHeHTOB. KaK noKa3ajm HauiH οπητμ, HHAHBHAyajn>Hbie Bemecroa 3THMH CBOHCTBaMH Ηβ 00JiaAai0T HJIH 00JiaAaiOT TOJIbKO B He3HaHHTejIbHOH Mepe.

PemaiouļeH ķrk cTa6HJiH3au;HH ηβληθτοη AodaBKa MoneBHHbi h pa3AHHHbIX aMHHOKHCAOT. MOHeBHHa HCnOJIb3yeTCH B KOJIHHeCTBe 5-50 γ/ji, npeAnoHTHTejibHO 10 - 15 γ/ji. B KanecTBe aMHHOKHCJioT c;ieAyeT Ha3BaTb, HanpHMep, tjihhhh, ajiaHHH, aprHHHH, L - jiefiuHH, 2 - φβΗΗΛΒΛΒΗΗΛ, TJiyTaMHHOBaH KHCJIOTa HJIH L - TpeCHHH. CMeCH pa3JIHHHbIX aMHHOKHCJIOT, nO-BHAHMOMy, HMeiOT OCo6eHHO npeAnOHTHTeJIbHblH 3φφεκτ. LV 10393

Mx Hcnojib3yiOT b KOJiHHeciBe 0,5-50 γ/ji, npeanoHTHTejibHo 1-20 γ/ji, npHneM o6mee KOJuraecTBo aojdkho cocrraBjiHTb npeAnoHTHTejibHO 5-25 r/jī. Ķsuiee, Ηβθ6χθΑΗΜ φΗ3ΗΟΛΟΠΙΗβΟΚΗΗ COBMeCTHblH όγφβρ, KOTOpbIH B Ηβθ6χθΑΗΜΜΧ ĶJIR HHb6Kl|HOHHbIX paCTBOpaX He3aHHTeJIbHbIX KOHiieHTpajnHBX npHMepHO 20-100 mmojib/ji/ ycTaHaBJiHBaeT Heo6xoAHMyio AJia EPO pH - odjiacTb 6,5 - 7,4, b oco6eHHocTH 7,0 - ,2. KpoMe φοοφΒΤΗΗΧ 6yφepoB πρκΜβΗΗΜΗ TaKMce πιηιιηηητ, Kap6oHaT, HHTpaT h Apyrne, npHneM b Kanecrae προτΗΒΟΗΟΗΟΒ Moiyr cjiyacHTb, KpoMe hohob HaTpHH h KajiHH, TaKMce ηοημ βμμοηηη. ByφepHpoBaHHe AonojiHHTejibHO Bbi3biBaeTca coAepacaimiMHCH aMHHOKHCJioTaMH. īlpHJiHnaHHe EPO κ cremcaM aMnyji h mnpHiiaM cym;ecTBeHHo CHHacaeTCH 3a craeT Ao6aBKH He3HaHHTejibHbix KOJuraecTB AeTepreirra. TaK KaK npenapaT AOJiaceH npeAnoHTHTejibHO BBOAHTbcn nyreM HHbeKiiHH, 3to BemeCTBO AOJIHCHO 6bīTb φίί3ΗΟ JĪOrmeCKH, B OCodeHHOCTH BHyTpHBeHHO, COBMeCTHMO. OKa3bIBaiOTCH ΠρΗΓΟΑΗΗΜΗ KOHlieHTpaiļHH 0,05 - 5 γ/ji, B oco6eHHOdH 0,1 - 0,5 r. HeHOHHbie CManHBaTejm, KaK pa3JiHHHbie bham no JiHMaKporo jiob, b ocodeHHocTH noaH3THaeHcop0HTaHJiaypaT /Tbhh 20 hjih 80/ hjih cop0HTaHTpHjieaT /S pan 35 hjih 80/ hjih nojmrjiHKOJieBbiH 3φκρ rjiHii;epHHOJiexjiOBOH KHCJioTbi /L abrafi 1^/ 0Ka3biBai0TCH πρηγοαηβιμη AJia 3T0H uejiH, oAHaKo, BpaBHoft Mepe MoryT Hcnojib30BaTbca Apyrae coBMecTHMbie BemecTBa. ZUh yMeHbiueHHH bjihhhhh Ha EPO hohob Taacejibix MeiajuioB, κοτορΗβ ποητη HeH30excHO yBJi6KaioTCK npH o6pa6oTKe, HanpHMep, H3 Hcnojib3yeMbix MeTajuiHHecKHX HHCTpyMeHTOB, Aajiee, OKa3biBaeTca npHroAHHM Ao6aBJieHHe pacTBopa 0,01 - 5 γ/ji pacTBOpHMOH KajībHHeBOH cojih, npeAnoHTHTejibHo npHMepHO 0,02 - 0,2 γ/ji xjiopHAa KajihiiHH. Tanace MOryT HCnOJIb30BaTbCH ApyrHē φH3HOJIOΓHHeCKH COBMeCTHMbie K0MnjieKcoo6pa30BaiejiH, HanpHMep, umpaT, E/1TA, MTA, naHTOTeHāT.

B KanecTBe pacTBopHTeJia Hcnojn>3yK)T HHCTyio BOAy ķjik HHbeKHHOHHbIX IļeJieH, K KOTOpOH AJIH yCTaHOBJieHHa H30T0HHH Ao6aBJIHK)TCH eme 0,5 - 10 γ/ji xjiopHAa HaTpHH hjih οοοτΒβτcTBy ιοιιιηχ BemecTB, KaK

MaHHHT, COp0HT Η T.A· Jļjin nojiyneHHH npenJiaraeMbix corjiacHO H3o6peTerono npenapaTOB Bce BcnoMoraTejibHbie BeniecTBa pacTBopniOT b Heo6xoAHMOM KOjuraecTBe BOAbI, npHMeiHHBaiOT EPO - npenapaT KOTOpbIH AOJDKeH HMeTb aKTHBHOCTb npHMepHO 100 000 - 200 000 eAHHHii;/μγ npoTeHHa, cTepHJībHo φHJIbτpyIOT b C00TBeTCTByK)iHHe aMnyjibi, 3aMopaacHBaiOT h ocTOpoacHo JIHoφHJIH3Hpyκ)T npH hh3khx TeMnepaTypax. IIojiyHeHHbie npenapaTbi ycTOHHHBbi b ΒΤΜοοφβρβ a30Ta b TeneHHe 2-x JieT npn 0°C, h b Tenemie 1 ro^a npn KOMHaTHoft TeMnepaType. Πρκ peKOHCTtnyHpoBaHHH c noMoiiļbio boam ohh pacTBopaioTCH 3a HecKOJibKo ceKyHA 6e3 noMymeHHH h TaKHM odpa30M MoryT npHMO BBOAHTbCH nyTeM BHyTpHBeHHOH HJIH BHyTpHMbimeHHOH HHbeKHHH hjih nocjie pa36aBJieHHH H30TOHHnecKHMH pacTBopaMH /HanpHMep, paCTBOpOM XJIOpHAa HaTpHH/ BJIHBaTbCH. īlponeccy 3aMopaacHBaHHH npHAaioT oco6oe 3HaneHHe. BeHOMoraTejibHbie BemecTBa no poAy h KojmnecTBy Bbi6HpaiOTCH TaK, hto6h 3BTeKTHMecKaH TOMKa 3aMopa»CHBaeMoro pacTBopa Haxo^H^acb Me»CAy - 50° h - 30° C. C ΠΟΜΟΙΒΒΚ) ynpaBJiaeMOH KOMIIblOTepOM npOrpaMMbl OnTHMH3aiļHH onpe^e^HJiHCb cjiejņiouņie onTHMajībHbie ycjioBHH λλη 3-χ φ33 ΛΗθφΗΛΗ3ΗΗΗΗ:

BpeMH 3aMopaxcHBaHHa: 12-14 aacoB npH - 40°C; ocHOBHaa cyuiKa: TeMnepaTypa paccoaa + 10°C, flaeaeHHe 10“1 M6ap, BpeMH 48 - 60 nacoB; λοποληητeHbHan cynnca: TeMnepaTypa paccoaa + 20°Ct ZiaBJieHHe 10"3 M0ap, BpeMH 4-6 nacoB. ΠρΗ 3TOM CymeCTBeHHbIM HBHHeTCH pacn03HaBaHHe C nOMOIIļblO H3MepHTeHbHoro ycTpoiicTBa Δ p, a Tarafce H3MepeHHe ΒΛβκτροπροΒΟΛΗοσίΉ, Kor^a 3aKOHHHTCH OCHOBHaH CyiUKa, HT00bI ΛHOφHΛH3HpyeMbIH npO/tyKT CHHIHKOM 6bICTpO Ηβ HarpeBajICH H HT00bI H30eraTb OTTaHBaHHH 3aMOpOHCeHHOrO paCTBOpa H CBH3HHOH C 3THM nOTepH aKTHBHOCTH.

Hcnojn>3yeMbie BcnoMoraTejihHbie BeinecTBa BH0HpaiOTCH TaK, hto6h ocyiu;ecTBHHHOCb o6pa30BaHHe paBHOMepHO cTpyicrypHpoBaHHoro jmc^HJiH3HpyeMorc> 3aMep3inero Tejia h bo BpeMH ληοΦηλη33Ι1ηη nojiyHaj[CH IĪOpHCTblH CKeneT / OCaflOK Ha φΗΗΒΤρε/, H3 ΚΟΤΟρΟΓΟ B03MO)KHa onTHMajībHaH cy0HHMauHH Hb^a, npeacAe Bcero TaKHce κ KOHii;y ochobhoh cyniKH. /ļonoHHHTeHbHaH cyuiKa ocymecTBJineTCH, KaK yKa3aHO Bbirne, TOJibKO npH + 20°C, b TeneHHH 4-6 nacoB. 3īa oeTopoMCHan o6pa6oTKa ηβληθτοη BajKHOH, TaK KaK HHaHe πρκχοΛΗΤ κ ποτβρβ ηκτηβηοοτη b cjiynae chhihkom ΛHoφHΛH3HpoBaHHOΓo MaTepnajia.

KaK npaBHJĪO, TaKHM o6pa30M ΛΗθφΗΛΗ3ΗρθΒ3ΗΗΗβ npOflyKTbI ΗΜβΙΟΤ coaepHcaHHe βολή no K. <X>mnepy npnMepHO 2-5%, 3to ociaTOHHoe COflepHCaHHe ΒΟΛΗ 3aBHCHT ΟΤ ρΟΛΛ H KOJIHHeCTBa BCnOMOraTeHbHbIX BemecTB, κοτορπβ ncnojib3yioTCH b cooTBeTCTByiomeH peneniype. ΒοΛΗΒΙβ paCTBOpbl CTa6HHH3 Ηρ0Β3ΗΗ0Γ0 EPO MOJKHO TaKHCe ΗβΠΟΟρβΛΟΤΒβΗΗΟ 3aJIHBaTb B aMnyjIbI H 6e3 ΛΗθφΗΛΗ3ΛΙ1ΗΗ B ΒΗΛ6 ΓΟΤΟΒΟΗ K ynOTpe6jieHHK) φορΜΗ HCnOJIb30BaTb. ΥΟΤΟΗΗΗΒΟΟΠ» ΟΛΗΛΚΟ 0Λ3Γ0Λ3ρΗ 3TOMy ΠΟ CpaBHeHHĪO C ΛΗθφΗΛΗ3ΛΤΟΜ COKpaiIiaeTCH ΠρΗΜβρΗΟ ΛΟ 1 ΓΟ/ļa npn 0 C h HecKOHbKHx MecHiļeB npn κομηλτηοη TeMnepaType. HH>KecjieAyK>inHe npHMepbi λοληοιη 6ojiee πολρο6ηο ποηοηητβ BHineonHcaHHoe: ΠρΗΜβρ 1

CyXOe BemeCTBO ΛΛΗ HHbeKlļHH C 2000 βΛΗΗΗΙΙ 3pHTpOnOH3THHa /cocxaB λλη 35000 aMnyji/

B CTepHHbHOM, cHa6xceHHOM MemajiKOH, eMKoeTbK) 100 ji 2A pe3epByape c λβοηηοη py6aimcoH pacTBopnioT BcnoMaraTejn>Hbie BeinecTBa: MOHeBHHa 700,0 r ΧΛΟρΗΛ HaTpHH 70,0 r Tbhh 207,0 r 7,0 r ΛΗΓΗΛροφοοφΛΤ HaTpHH X 1 H2O 38,4 r LV 10393 /ΙΗΗ3ΤρΗΗΠΙιΖΐρθφθθφ3Τ X 2 350,0 r XJIOpH/l KaJIbnHH X 2 H2O 8,4 r rJIHIIHH 105,0 r L - JieimMH 140,0 r L - H30JieHU,HH 140,0 r L - TpeOHHH 35,0 r L - rjijrraMHHOBan KHCJioTa 35,0 r L - φβΗΐυ^ΒΗΗΗ 70,0 r BOJia ΚΛΆ HHĪ>eKIIHOHHbIX nejien JļO 70,0 ji K 30 ji 3τογο BcnoMoraTejibHoro pacTBOpa flo6aBJiflioT 214,3 μλ cbipbeBOH 3arpy3KH apHTponoaTHHa c thtpom EPO 140 000 en. /mji. h aojiHBaiOT λο KOHeHHoro o6beMa 35 ji h nepeMeuiHBaioT. C noMontbio ocTajībHoro pacTBOpa BcnoMoraTejibHbix BemecTB cnojiacKHBaioT cHcreMy φΗ^τρ3ΐίΗΗ. PacTBop cocTaBa CTepHJībHO (ļ)HJibTpyK)T nepe3 MeMdpaHHbrii φΗΛΒΤρ C pa3MepOM nop 0,2 MKM. CTepHJIbHO ΠρθφΗΛΒΤρθΒ3ΗΗΒΙΗ paĢTBOp B aceiITHHeCKHX yCJIOBHHX 3aJIHBaiOT B CKJMHKH Ķjm ΗΗΒβΚΙΙΗΗ eMKOCTbK) 1 MJI H Cy6jIHMaiIHOHHO BbIcyiUHBaiOT B yCTaHOBKe ΚΆΆ JIHC^PiJIH3aiIHH npH cjieAyioiu:HX κρκτερΗίΐχ: ΒρβΜΛ 3aMopaMCHBaHHH: 12-14 nācos npH - 40°C, ocHOBHaH cyniKa: TeMnepaTypa paccojia + 10°C, HBJieHHe 10"^ M0ap, BpeMH 4-6 nacoB.

nojiynaioT TaKHM o6pa30M o6beMHCToe, c οτκρμτημη nopaMH cyxoe BemecTBO zūjih HHbeKiļHH, κοτοροβ CTa6HJibHO no KpaftHefi Mepe 2 ro^a b xojio^HJibHHKe η 1 γοκ npH KOMHaTHOH TeMnepaType h b Teneroie HecKojibKHX HacoB pacTBopHeTCH b 2 mji βοαμ κλά ΗΗΒβκηηοΗΗΗχ nejieft 6e3 noMyraeHHH H JIHIIieHHblM MaCTHII, IIpHMep 2

ϋκοφη jiH3aT £ 200 enHHHnaMH 9pHTpOIIOH3THHa /cociaB ajih 35 000 aMnyji/ 46,7 mji = 7 Mic efluroiu; 100.0 r 10.0 r 155.0 r 500.0 r 10.0 r 1000,0 r

3pHTpOnOH3THH XJIOpHfl HaTpHH

Tbhh 20 ΑΗΓΗΑθφθθφ3Τ ΗΒΤρΗΗ X 1 H2O ,Ζ1ΗΗ3ΤρΗΗΓΗΛρθφθθφ3Τ X 2 H2O XJIOpHfl KaJIbUHH X 2 H2O MOHeBHHa 150.0 r 120.0 r 165.0 r 70.0 ji

L - JieHIIHH

TpeOHHH φβΗΗΛΜΕΗΗΗ

BOfla ĶJin ΗΗΈβΚΙΪΗΟΗΗΒΙΧ ΠβΛβίί ĶO

BcnoMoraTejibHbie BemecTBa pacTBopaioT κλά Hin>eKiļHOHHbix iļejieft h 3aTeM pa3/i;ejiHK)T Ha 2 nopnrai no 35 λ. IlepBbie 35 ji cMeniHBaiOT c Heo6xOjHHMbIM KOJIHHeCTBOM EPO - 6HOJIOTH4eCKH aKTHBHOTO BemeCTBa. ΒτορΗβ 35 ji Hcnojib3yioT ķjik cnojiacKHBamiH CHCTeMM φηJibTpaiļHH. PacTBOp cocTaea cTepnjibHO φηΛΒτργιοτ nepe3 M6M0paHHbiH φηΛΜρ c pa3MepOM nop 0,2 MKM. CTepHJttHO ΠρθφΗΛΒΤρθΒ3ΗΗΒΙΗ paCTBOp npH acenTHHeCKHX yCJIOBHHX pa3JIHBaK)T B CKJMHKH flJIH HHbeKIļHH eMKOCTbK) 1 MJI H JIHoφHJIH3HpyK)T npH ΤβΧ 3Κβ KpHTepHHX, KaK yKa3aH0 B npHMepe 1. IlojiyHaK)T TaKHM o6pa30M 6ejioro iļBeTa, nopiiCTbift, χοροπιο pacTBopHMHH b 2 ΜΛ BOflbl ΛΗθφΗΛΗ33Τ, KOTOpbIH MOJKeT XpaHHThCH 6β3 όΟΛΒΠΙΗΧ ΠΟΤβρΒ aKTHBHOcTH 2 ro/ļa b xojioflHJibHHKe hjih 1 γολ npn KOMHaTHOH TeMnepaType. ITpMMep 2

ϋκοφη jiH3aT c 1000 e JHHHnaMH 3pHTpOnOH9THHa /cocTaB ĶJia. 35 000 aMnyji/ 233,33 mji = 7 Mic emīram 100.0 r 12.0 r 140.0 r 450.0 r 10.0 r 700.0 r 92.0 r 103.0 r 115,5 r 70.0 λ

BpHTponOHBTHH XJIOpHA Η3ΤρΗΗ Tbhh 20

ΛΗΓΗΛΟφοοφΒΤ HaTpHH X 1 H2O ΛΗΗΗΤρΗΗΓΉΛροφοοφΒΤ X 2 ί^Ο xjiopH<n; KajībiiHH x 2 H2O MoneBHHa L - JieftiiHH

rjiyTaMHHOBan KHCJioTa φeHHJIaJIaHHH

Bozta jļjiH HHi>eKnHOHHbix nejieft ΛΟ

BcnoMoraTejtbHbie BemecTBa pacTBopaioT b 70 ji βολμ ακη HHbeKii;HOHHbīx nejieii n 3aTeM pa3^ejmiOT Ha 2 nopiļHH no 35 λ. IlepBbie 35 ji cMemnBaioT c Heo6xoAHMbiM KOJumecTBOM EPO - 6HOJionmecKH βκτηβηογο BemecTBa. Bīopbie 35 ji Hcnojib3yioT pjisi cnojiacKHBamiii cncTeMbi φκjibTpauHH. PacTBop cocTaBa cTepnjibHO φHJIbτpyκ)τ nepe3 MeM0paHHbiH φΐυΐΒΤρ C pa3MepOM nop 0,2 MKM. CTepHJIbHO ΠρθφΐυΐΒΤρθΒ3ΗΗΒΙΗ paCTBOp npH acenTHMeCKHX yCJIOBHHX 3ajIHBaiOT B CKJIHHKH RāK HHbeKIIHHēMKOCTblO no 1 mji h JIHoφHJ^H3HpyĶ)τ npH Tex »ce κρητερΗΗΧ, KaK omicaHO b npHMepe LV 10393 1. nojiyMaioT τεκημ o6pa30M 6ejioro uBeTa, nopHCTbiH, χοροιπο paCTBOpHMblft B 2 MJI BOAbI ΛΗθφκ JIH3aT, KOTOpblH ΜΟΪΚβΤ XpaHHTbCH 2 ΤΟΚΟ. b xojio^HJibHHKe hjih 1 γοα npH KOMHaTHOH TeMnepaType, 6e3 6ojibiimx nOTepb aKTHBHOCTH. Π p η m e p 4 )1ΐ1θφΐυΐΗ33Τ C 500 eJHHHliaMH 3pHTpOIIOH3THHa /cocīaB }\λά 35 000 aMnyji/

3pHTpOĪIOH3THH 116,67 MJI = 17,5 Mic e^HHHII XAOpHA HaTpHH 70,0 Γ 7.0 r 38.0 r 490.0 r 5,6 r 840.0 r 92,4r 105.0 r 119,0r 70.0 a

Tbhh 20

ΛΗΓΗΛθφθθφ3Τ HaTpHH X 1 UļO ΑΗΗ3ΤρΗΗΓΗΑρθφθθφ3Τ X 2 H2O

XJIOpHA KajIbltHH x2 H2O MoneBHHa L - JieHHHH

rjiyxaMHHOBaji KHCJioTa φeHHJIaJIaHHH BO^a ajih HHbeKHHOHHbix uejiež ao

BcnoMoraiejibHbie BeinecTBa pacTBopnioT b 70 λ βολή rjw. HHbeKu;HOHHbix iļejieft h 3aTeM pa3AeJiHK)T Ha 2 nopiiHH no 35 ji. IlepBbie 35 ji cMeniHBaiOT c ΗβοόχοΑΗΜΜΜ KOjnmecTBOM EPO - 6HOJiortrqecKH aKTHBHoro BemecTBa. BTopbie 35 ji Hcnojib3yioT ķjik cnojiacKHBaHnn CHcreMH aah φΗΛΒτρΒίίΗΗ. PacTBop cocTaBa crepHJībHo φnJIbτρyκ)τ nepe3 MeM6paHHHH φΐυΐΒΤρ C pa3MepOM nop 0,2 MKM. OrepHJIbHO πρθφΗΛΒΤρθΒ3ΗΗΗΗ paCTBOp pa3JiHBaiOT npn acermmecKHX ycjioBHnx b ckjihhkh κλά HHbeKiļHH eMKocTbio no 1 mji h JmoφHJIH3HpyIoτ πρη τβχ xce κρΗτερπηχ, KaK yKa3aH0 b npnMepe 1. riojiynaiOT τβκημ o6pa30M 6ejioro iiBeia, nopncTbift, χοροιπο paCTBOpHMblft Β 2 MJI BOflbl JIHoφHJIH3aT, KOTOpblH MCDKeT XpaHHTbCH 6e3 6ojibumx noTepb aKTHBHocra. 2 roAa b χολοαηλβηηκβ hjih 1 γοα πρκ KOMHaTHoii TeMnepaiype.

IlpHMep 5. JI ΗθφΗ AH3aT £ 75 0 e JHHHnaMH 9pHTponOH3THHa /cocīaB aah 35 000 aMnyA/ 3pHTpOnOH3THH ΧΑΟρΗΑ HaTpHH Tbhh 20 175,0 ma = 26,25 Mio eAHHHii 70.0 r 12.0 r ΑΗΓΗΛθφθθφ3Τ HaTpHH X 1 H2O 140,0 r ,3ΗΗ3ΤρΗΗΓΗ/φθφθθφΗΤ X 2 P^O 450,0 r XJIOpHA KaJIbLIHH X 2 H2O 10,0 r MOHeBHHa 1250,0 r H30JieHHHH 98,0 rjiyraMHHOBaH KHCJIOTa 130,0 r φβΜυ^ΒΗΗΗ 145,0r Bo^a ķjik HHbeKHHOHHbix nejieii ΛΟ 70,0 ji

BcnoMoraiejibHbie BemecTBa pacTBOpaioT b 70 λ βοαμ απη HHbeKiiHOHHbrx nejieH h 3aieM pa3#eji;noT Ha 2 nopnmi no 35 ji. IlepBbie 35 JI CMeniHBaiOT C ΗβοόχΟ/ΙΗΜΗΜ KOJIHHeCTBOM EPO - όΗΟΛΟΓΗΗβΟΚΗ aKTHBHOrO BemecTBa. Biopbie 35 ji Hcnojib3yiOT jj,jw cnojiacKHBaHHH cncTeMbi κλά φιιjibTpaiļHH. PacTBOp cocTaBa crepHjībHo φη;Π)Τρ7Κ)τ nepe3 MeM6painn>iH φκ./π>τρ c pa3MepoM nop 0,2 mkm. CTepHJiLHO προφ^ΒτροΒΒΗΗΗΗ pacTBop pa3JiHBaiOT npn aceimiMecKHX ycjioBHiix b ckjihhkh ūjm HHi>eKiiHH eMKocTbio no 1 mji h JIHoφHJIH3Hpyκ)τ npH Tex »ce KpHTepHHX, KaK yKa3aHO b npHMepe 1. ĪIojiyHaioT t3khm o6pa30M 6e;ioro nBera, nopHCTbift, χοροιηο paCTBOpHMblH B 2 MJI BOflbI ΛΗθφΐυΐΗ33Τ, KOTOpbIH MOJKeT XpaHHTbCfl 6β3 6oJIbUIHX nOTepb aKTHBHOCTH 2 rofla B XOJIOAHJIbHHKe HJIH 1 ΓΟΛ npn KOMHaTHoft TeMnepaType. Π ρ η m e p 6 Jļjlil ΤΟΓΟ, HTo6bI HCnblTaTb 3φφβΚΤΗΒΗΟΟΤΒ pa3JIHHHbIX CTa6njra3aTopoB, ctaH/iapTHyio peneirryy c 1000 e^. EPO/mji, KOTopan co^epjKHT b KanecTBe ochobhoio CTa6njiH3aT0pa MoneBHHy, CMeniHBaiOT co CMeCbK) nOJIHBHHHJinHppOJnmOHa c 6eJIKOM, COOTeTCTBeHHO, pa3JIHHHbIMH MHHOKHCJioTaMH η προ^κτΗ jnK^HJiH3npy ιοτ. Pe3yjn>TaTbi npe,ncTaBJieHHhi b Ta6jrane 1. CTa6njibHOCTb EPO nocjie 6 HeaeJīb xpaHeHHH JIHoφHJIH3aτa npn 35° C, οοοτβτοτΒβΗΗΟ, 0°C, b TecTe Ha cejie3eHKe μβιιιιη corjiacHO Μβτοηπκβ G. Krystal b Exp. Hematol. II, 649 - 660 /1983/, onpe^ejmeTca cjie^yiomHM o6pa30M:

CaMKaM B5C3F1 . Mbiinefi BecoM npHMepHo no 20 r /IļeHTpajībHbift MHCTHTyT zijih noKynaTejieH πολοπητημχ >κηβοτηηχ, raHHOBep/ b asa nocJieAOBaTejibHbix ληη bboahjih nyTeM HHbeKiiHH HHTpanepHTOHeajībHo 60 μγ/κγ φeHHJIΓHΛpa3HHΓHJ^poxJIopH/^a. CnycTH cjie/iyiomHe 3 ληη H3BJieKajiH cejie3eHKy, KJieTKH cejie3eHKH cycneH/iHpoBajiH b erepHJībHOH Komplett -cpe^e /Μθ,ιΐΗφΗΐΐΗροΒ3ΗΗ3ίϊ Eagle cpe^a Dilbecco + 584,0 mji/ji 1 -rjiyTaMHHa + 0,1 MMOJib/ji 2 - MepKaHTOBTanojia + 20% 3apo,abimeBOH LV 10393

TeJIOTbeft CbIBOpOTKH / H pa36aBJIHJIH £0 4 X 10^ 5mpOCO,aep>KamnX ΚΛβτοκ/mji. CycneH3Hio, κ κοτοροίί npejK/ie aodaBjraioT TecT - BeujecTBO, COOTBeTCTBeHHO, EPO - CTaH^apT, CMOTpH ΠΟ o6cTOHTeJIbCTBaM B ΠρκρΟΛΗΗΧ KOHiļeHTpanHHx, pacTBopeHHbie b BSA - όγφβρε, pacnpeAejunoT Ha njiacTHHKax ajih MHKpoTHTpa /0,2 mji/yrJiy6jieHHe/. īlocjie HHKy6aiiHH /22 qaca, 37° C, B03Ayx 15%C02 /Ha yrjiy6jieHHe aodaBJinioT 20 mkji 3h -ΜβΤΗΛ - τημηαηηοβογο pacTBopa c 1 MCI h cHOBa ΗΗκγόκργιοτ 2 qaca npn 37° C. īlocjie 3τογο co,a,epxcHMoe nepeBOAHT c noMombio κλθτοηηογο Harves H IIpOMblBaiOT C nOMOUļbK) β - CUHHTHJIJIJIIIHOHHOrO CHeTHHKa Η ΟΗβΗΗΒΒΙΟΤ no OTHomeHHio κ CTaHflapTHMM npenapaTaM. B KanecTBe padonero craimapTa ncnojib3yioT "POO - EPO - craimapT" HHCTmyTa reHeTHKH, KeMdpHflJK, MaccaHyceTC, CIIIA, κοτορΗΗ co^epacHT 112 ejļ. EPO/mji h 503 ηγ npOTenHa /mji/ [ypaBHeHHbin no oTHomeHHio κ EPO - cTaH^apTy WHO "International Reference Preparation of Erythropoietin, Human, Urinary for Busay 12 no I.R.P., established" 1971]. CaHAapTHbie KOHiieHTpaiļHH Haxo/iHTCH b odjiacra 10-100 hiV/mji.

McnblTblBaiOIIIHeCH Ha EPO - aKTHBHOCTb ΛΗθφΐυΐΗ33ΤΗ CHanajia, Ha aMnyjiy, pacTBopHJin b 2 mji βολή ajih ΗΗΒβκιιηοΗΗΗχ iļejieft, ocymecTBJinjiH AajībHeftniHe pa36aBJieHHH - TaiOKe KaK b cjiyHae padonero craHflapia - c noMombio BSA - 6γφερη /8,75 r NaCI, 1,95 r CaCl2 χ H2O, 1,00 r BSA/ dbiHHŽ cbiBOpoTOHHbin ajibdyMHH φκρΜΜ Calbiochem/, Bojia ķjik HHbeKiļHOHHbix ijejieH λο 1 ji/. % - Meraji - thmhahh /yAejibHan aKTHBHOCTb: 2Ci /MMOJib/ nojiyHajiH ot Nev England Nuclear IIpHMep 7

TaKHM xce o6pa30M, KaK b npHMepe 6, HecKOJibKo H3MeHeHHyio HrraMMpenenTypy cMeniHBajiH c MoneBHHoft h pa3JiHHHHMH βμηηοκηοJioTaMH, COOTBeTCTBeHHO, CMecHMH. /Ijih cpaBHeHHH HccjieAOBajiH ABe coAepxcaiiiHe MaHHT peuenrypbi, KOTopbie cooTBeTCTByioT eBponežcKOMy naTeHTy 178665. Pe3yjibTaTbi npeflcraBJieHbi b Tadjiraje 2. LV 10393

Tadjmiļa 1 CocraB Mr/aMnyjiy 1 819892C a 819893H 6 8198411 a6 819985K 9pHTpOnOH3THH 1000 eA 1000 eA 1000 eA 1000 eA Mo^eBHHa 10,0 10,0 10,0 10,0 ΧΛΟρΗΛ HaTpHH 9,0 4,0 9,0 1,0 TBHH 20 0,1 0,1 0,1 0,1 ΑΗΓΗΑρθφθθφΒΤ HaTpHa X H20 0,55 0,55 0,55 0,55 AH- ΝΒ-ΓΗΑρθφθθφΒΤ X 2 h2o 5,0 5,0 5,0 5,0 CaCl2 X H2O 0,08 0,08 0,08 0,08 ΚΟΑΛΗΑΟΗ 12 ΡΓ 5,0 - 5,0 - ΓaJIaφyHAHH 1,0 1,0 - - ΓΛΗΙ1ΗΗ - 15,0 - 15,0 L - JieHIiHH - - 2,0 2,0 L - H30JieHIĪHH - - 2,0 2,0 L - TpeOHHH - - 0,5 0,5 L - rjiy6aMHHOBaH KHCJioTa - - 0,5 0,5 L-φβΗΗΛΛΗΗ - - 1,0 1,0 BOAa AOl,0 MJI Aol,0 mji Aol,0 MJI Aol,0 mji cta6mrbHOCTb πρκ 25°C 493 869 934 1128 CTaČHJIbHOCTb npH 0°C 985 1114 1144 1205 LV 10393 oo ο σ> ο σ> co οΟ) ιη ο Ο) co ο 05 CN Ο 05 Ο 05 Ο ο 05 05 05 00 00 05 00 Γ" 05 00 co 05 00 ιο 05 00 X Η 3 G ο 6ļ 2 \ u 2

o o Q io s. 00 o o , CM C0 CM LO CO co m CN ti 0) o O‘io o , l -r- T- , 1 T- | t T" * o vo ti <o 0,1 0,55 5,0 0,08 15 CM C0 CM_ LO , CD 1 O 1 CN <L> Ή 1 1 T- 1— l t— 1 1 ο . ιο « CN V 00 O

Ο . ΙΟ « CN Ο Ο ΙΟ X CN <U Ο ΙΟ fcļ CN Ο Ο ΙΟ X CN Ο Ο _ι ΙΟ Χ CN « νΟ « CN Ο Ο ^ ΙΟ te CN <U Ο j ΙΟ X CN <L> ΙΟ Χ CN Ο . ΙΟ fct CN <L> - lO ©^ O o VO O lO in ©_ th o-o" VO ©^ «o »n ©_ ° o vO o Ί iO ©_ ° θ' VO © vo « vo Ο T"< O © νο*' ©_ VO n VO ©_ ° ©* lO* ©_ vo vo ©_ ° © VO~ ©_ vo ^ VO O^ ° ©“ VO ©_ VO VO ©_ O ©‘ iO ©__ VO o_ ° o* vo" ©_ •^1 vo ©_ 1-H ° o VO ©^ VO Ί VO ©_ o o VO 00 o 00 o 00 o 00 o 00 o 00 o 00 o 00 o 00 o 00 o 00 o CN

l I CN CO in 1 CD I ·* * 1 CN h- ir) CO 1 CD 1 T-H 1 y— CN VO 1 CO CO 1 1 CN m 1 CO Νζ_ «o 1 • τΗ CN cn 1 CN t 1 T-H CN cn CN 1 1 ts^ "rH | CN CO CN I | Nl* r><_ «k ) CN CO CN l | Nj< rH CN r>- •K* cn 1 » 1 CN Nf cn 1 I 1 r^_ ** l CN r>- 1 CO 1 1 r^_ -r-< t—< CN i^. 1 CO 1 1 lO . Γ" VO CN o o - I o o Pn « co & » c3 n m . * ^ 9 Ο P* o w

« s Oh S b te CN S M cx w o b tļ 03 X H o CNXx S3 -&* o o Φ o 0h t[ ε κ

X 13 o o -θ* o α te s u « S Oh H

o CNXCN « B a A \ū oss o o t—I \ \ o te

te B Λ π O* Ss«g s «Sus

a l E a ’S § 1 g s R o t; co £ J K a H o t=! υ B B s « o X B S B g B rt s to B S B Λ fc! cS t: s B <u o CNXx·** B 2 Sm W H-HĒ *£

O K CN 2 x % ^ B o s Ph « CN S ώ ^s-aZ š ΜΛ MJT MJI MJI MJI MJI MJI MJI MJI MJI MJI MJI MJI MJI cTa6HjibHocTb 25bC 164 185 150 234 170 229 226 226 229 205 221 258 205 216 cTa6HJibHocTb 0°C 182 203 203 242 208 234 232 230 230 167 220 291 188 210

ο ο Η Η W ¢0 Ον Ον S S to V Xο3 tr Ο NJ Ο CA°<5 g ζ Ο 0?§ β to 53 to to Μ ΊΟκ Ο a ^ a * ο ^ ?! to C 1= Ε S' to ο Ζ £ Ό 3C to >ϋΟ 53 toΟ toο

ΓΟ CO Ό Ό Η-*-

Sto t-v O 5A O co ' 5A *- 1 to g“' ' O 00 O 5A Ca to Ca ΟΡ Ν-. ΛI-V Ο ί3 50 Ο 50 to rf* ο

Sto to — 1—V. P 5A P p P^· Ca O 05 1 CA »· 1 to 50 ' to O ' O 5—, 5A 00 0 Ca O s to co o to _ ca £ 05 to ►* © © O l/ι Ca 50 to 1-^ "o ^ Ό 00 CA s to 5a P Ol P O -* O00 © $ ~ © g 50 H*.to / ΟΗΙ135ΚΙΓOī/Odll / £ B ΪΙ H If 9 B χ o 50 to S 5a O to Ό to

>P» to 5a o Λ to 5A Ό 05 50 £ o to 5A Ό 5a 00 13 13 LV 10393 CDopMyjia H3o6peTeHHJĪ. 1. CoBMecTHbiii npenapaT ΗβΛΟΒβΗβακοΓΟ npoTeHHa, coAepacamHH MejioBeHecKHH προτβΗΗ, φΗ3Η0Λ0ΓΗΗββκΗ coBMecTHMbiž 6γφερ, a TaKJKe b cjiynae ΗβοόχοΑΗΜοβτη K0MnjieKcoo6pa3OBaTejib, ycTaHaB^HBaiomHe H30T0HHI0 CpēACTBa, ΧΛΟρΗΑ KaJIbUHH Η ΑΡΥΓΗβ, odblHHbie JļJlil HHbeKUHOHHbIX ΙΙ,βΛβΗ BeineCTBa, OTJIHMai01JŪ[HeCH ΤβΜ, HTO B HHbeKUHOHHOH φορΜβ COAepJKaTCH 5 - 50 γ/λ ΜΟΗβΒΗΗΒΙ, 1 -50 γ/λ aMHHOKHCjioTbi h 0,05 - 5 γ/λ AeTepreirra. 2. HeAOBeMecKHH προτβΗΗ no π. 1, oTJiHHaiomHeca τβΜ, hto b KanecTBe βμηηοκηολοτη coAepJKaTcn οαηβ ηλη ηθοκολβκο βμηηοκηολοτ h3 rpynnbl, ΒΚΛΙ0Η3Κ)ΙΙ1βΗ ΓΛΗΠΗΗ, ΗΛΗΗΗΗ, aprHHHH, L- ΛβΗΠΗΗ, L- Η30ΛβΗΙίΗΗ, 2 - φeHHΛaΛaHHH, rnyTaMHHOByio ΚΗβΛοτγ n L- TpeoHHH. 3. npenapaT Ha ocHOBe ΗβΛΟΒβΗββκοτο npOTenHa no π. π. 1 ηλη 2, o^HHaioinHecfl tcm, hto b KanecTBe AeTepreirra HcπoΛb3yκ)τ HeHOHHblii βΜΛΗΗΒΗΤβΛΒ. 4. npenapaT Ha ocHOBe ΗβΛΟΒβπββκοπ) npoTeHHa no n. 3 , ΟΤΛΗΗΗΙΟΙΠΗββΗ ΤβΜ, HTO B ΚΒΗββΤΒβ ΗβΗΟΗΗΟΓΟ 0Μ3ΗΗΒ3ΤβΛΗ HCΠOΛb3yK)T ΠΟΛΗ3ΤΗΛβΗβθρ0ΗΤ3Η Λaypaτ. 5. npenapaT Ha ocHOBe ΗβΛΟΒβπββκοπ) npoTeHHa no no ΛK)6oMy H3 π.π. 1 - 4, OT^HHaioiiiHeca τβΜ, hto npenapaT HaxoAHTCH b ΛΗθφΗΛΗ30Β3ΗΗΟΗ φορΜβ. 6. npenapaT Ha ocHOBe ΗβΛΟΒβΗββκοτο npoTeHHa no ΛK)6oMy H3 π.π. 1 - 4, otJiHnaiomHeca τβΜ, hto npenapaT HaxoAHTcn b hchakoh, CnOC00HOH ĶJIR BnpblCKHBaHHH φορΜβ. 7. npenapaT Ha ocHOBe ΗβτοΒβΗββκοΓΟ npoTeHHa no ΛIo6oMy H3 π.π. 1 - 6, OT^HHaioinHeca τβΜ, hto Ha eAHHHny αο3μ ΗΗΒβκηΗΗ 1 - 5 μλ COAepJKHTCH 100 - 1 ΜΗΛΛΗΟΗ eAHHHH ΗβΛΟΒβΗββΚΟΓΟ npoTeHHa. 8. npenapaT Ha ocHOBe ΗβΛΟΒβΗββΚΟΓΟ npoTenna no πτοόοΜγ H3 π.π. 1 - 7, ot JiHHaKiiiiHeca τβΜ, hto ΗβΛΟΒβπββκΗΗ προτβΗΗ ηβληθτ ch apHTponosTHH. 9. npenapaT Ha ocHOBe ΗβΛΟΒβΗββΚΟΓΟ npoTeHHa no n. 8, OTJIHHaiOIIIHeca TeM, HTO Ha eAHHHny ΗΗΒβΚΙίΗΟΗΗΟΗ A03bl 1 - 5 ΜΛ coAepHcaTcn 100 - 20 βΑΗΗΗΐι; spHTponoaTHHa. LV 10393 AHHOTaiļHH. M3o6peTeHHe OTHOCHTCH K COBMeCTHMbIM, yCTOHHHBbIM npH XpaHeHHH npenapaTaM HejioBeMecKoro npoTeHHa, co^ep>Kaiu;HM HejioBenecKuS προτβΗΗ, B OCo6eHHOCTH 3ρΗΤρ0Π03ΤΗΗ, φΐΟΗΟΛΟΓΗΗβΟΚΗ COBMeCTHMbie όγφβρΒΙ, a TaKJKe npH H3BecTHbix ycjioBHHX KOMiuieKcoo6pa30BaTejin, ycTaHaBJiHBaio]HH6 H30T0HHI0 Cpe/tCTBa, ΧΛΟρΗΛ KaJIblļHH H Apynie, o6bIHHbie Ķjm HHbeKIļHOHHbIX UeJieft BeilļeCTBa, H, KpOMe ΤΟΓΟ,Β HHbeKlIHOHHOH φορΜβ 5 -50 τ/λ ΜΟΗΘΒΗΗΒΙ, 1-50 r/jl aMHHOKHCJIOTbl, 0,05 - 5 γ/λ ΗβΗΟΗΗΟΓΟ cMaHHBaTejiH, h cnoco6y hx noJiyHeHHH.

Claims (9)

1. LV 10393 Izgudrojuma formula 1. Saderīgs cilvēka olbaltumvielas preparāts, kas satur cilvēka olbaltumvielu, fizioloģiski saderīgu buferšķīdumu, nepieciešamības gadījumā arī kompleksveidotāju, izotoniju nodrošinošus līdzekļus, kalcija hlorīdu un citas, injekcijas līdzekļiem parastas vielas, a t š ķ i r a s ar to, ka injekcijas formā ir 5 - 50 g/l urīnvielas, 1 - 50 g/l aminoskābes un 0,05 - 5 g/l virsmas aktīvas vielas.
2. 2. Cilvēka olbaltumvielas preparāts pēc punkta 1, kas a t š ķ i r a s ar to, ka par aminoskābi tiek ievadīta viena vai vairākas aminoskābes no grupas: glicīns, alanīns, arginīns, L-leicīns, L-izoleicīns, 2-fenilalanīns, glutamīnskābe, L-treonīns.
3. 3. Cilvēka_olbaltumvielas preparāts pēc punkta 1 vai 2, kas a t š ķ i r a s ar to, ka par virsmas aktīvo vielu tiek izmantots nejonogēns slapinātājs.
4. 4. Cilvēka olbaltumvielas preparāts pēc punkta 3, kas a t š ķ i r a s ar to, ka par nejonogēno slapinātāju izmanto polioksietilēnsorbita laurātu. 1
5. 5. Cilvēka olbaltumvielas preparāts pēc jebkura no punktiem 1 - 4, kas atšķiras ar to, ka preparāts ir liofilizētā formā.
6. 6. Cilvēka olbaltumvielas preparāts pēc jebkura no punktiem 1 - 4, kas a t š ķ i r a s ar to, ka preparāts ir šķidrā, injekcijām piemērotā formā. 1«
7. 7. Cilvēka olbaltumvielas preparāts pēc jebkura no punktiem 1 - 6, kas a t š ķ i r a s ar to, ka 1 - 5 ml injekcijas devā ir 100 - 1 000 000 vienību cilvēka olbaltumvielas.
8. 8. Cilvēka olbaltumvielas preparāts pēc jebkura no punktiem 1 - 7, kas atšķiras arto, ka cilvēka olbaltumviela ireritropoetīns.
9. 9. Cilvēka olbaltumvielas preparāts pēc punkta 8, kas a t š ķ i r a s ar to, ka 1 - 5 ml injekcijas devā ir no 100 līdz 20 000 vienību eritropoetīna. 2