LV10965B - Process for producing of compositions conteining hyaluronic acid associate - Google Patents
Process for producing of compositions conteining hyaluronic acid associate Download PDFInfo
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- LV10965B LV10965B LVP-93-747A LV930747A LV10965B LV 10965 B LV10965 B LV 10965B LV 930747 A LV930747 A LV 930747A LV 10965 B LV10965 B LV 10965B
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- 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
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- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/58—Metal complex; Coordination compounds
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Birds (AREA)
- Inorganic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Description
LV 10965
CnOCOB ΠΟ/ΊΥΗΕΗΜΗ K0Mn03MUMfi HA OCHOBE ACCOUMATOB (KOMflflEKCOB) flEnPOTOHMPOBAHHOfi ΓΜΑ/ΙΥΡΟΗΟΒΟΜ KMCJlOTbl
OnncaHue Μ3θ6ρθΤΘΗΜΘ 0TH0CMTCH K Cn0C06y ΠΟΠγΗβΗΜΑ Κ0ΜΠ03Μ14ΜΜ Ha OCHOBe HOBblX accounaTOB (κομππθκοοβ) penpoTOHMpoBaHHOM rManypoHOBOM κμοποτη c μοηθμμ 3d MeTannoB ηθτβθρτογο nepMopa nepMopMnecKOM Ta6nnubi h οοθρμηθημμ. B οοοτβθτοτβμμ c npennoHTmenbHbiM BapnaHTOM ocyiyecTBneHMfl HacToamero n3o6peTeHna BOflHbie paTCBopbi, copepjKamne HOBbie accounaTbi penpoTO-HMpOBaHHOM rnanypOHOBOii KMCriOTbl C M0H3MM 3d ΜΘΤ3ΠΠ0Β ΗΘΤΒΘρΤΟΓΟ ΠΘρΜΟΡβ nepnopunecKOM Ta6nnubi, HenocpepcTBeHHO nonyna»OT H3 βορηογο pacTBopa rnanypoHaTa Haipna. B ΟΟΟΤΒβΤΟΤΒΜΜ C HaCTOflLUMM Μ3θ6ρθΤΘΗΜΘΜ HOBbie aCCOUHaTbl maBHbIM o6pa30M αβπηιοτοα rnanypoHaiaMM 14uhKa m KodanbTa. Κομπο3μι4μμ, copep^amtie 3th accounaTbi, Moiyr Mcnonb30BaTbCB b KanecTBe φ3ρΜ3ΐ4βΒΤΜΗβοκΜχ (TepaneBTHHecKnx) μπμ κοομθτμηθοκμχ cpepCTB. OānacTb πρΜΜβΗβΗΜ* Κ0ΜΠ03ΜΙ4ΜΜ, COqep>KaiUMX HOBbie aCCOUHaTbl, B COOTBeTCTBUM C HaCTOflmMM Μ3θδρβτβΗΜΘΜ pacnpocTpaHfleTca HanpMMep, Ha: ycKopeHMe npoueccoB 3ΠΜΤβΠΜ3314ΜΜ yHaCTKOB Teņa, 3a>KMBneHMe 6enpeHHblX fl3B, ΠρθΠβ>ΚΗβΜ. TnaBHblM o6pa30MT He3a>KMBaiomMX paH, οχογοβ, ποοπθροτβμμ papMapMM μ τθπποβογο B03fleMCTBMH, BocnaneHMM canbHOM >Kene3bi, a Tao<e ohm πρμμθηαιοτοη m b qpyrMx o6nacTBx. ΓManypoHOBaa KMcnoTa npepcTaBnaeT οοβοίί MaKpoMoneKyny. OHa 6bina nonyneHa 6onee πατμρθοητμ πβτ Ha3aq m enepBbie onMcaHa MeūepoM (J. Biol. Chem. 107, 629 (1954), J. Biol. Chem. 114, 689 (1936)). OnMcaHMe CTpyKTypbi 6bino npepcTaBneHO BeiicMaHOM (J. Am. Chem. Soc. 76, 1753 (1954)). rManypoHOBaa KMcnoTa npepcTaBrmeT co6om npMpopHbiii γπμκοβθμμηγπμκθη BbicoKoii bh3koctm, COflep>KaLHMM miOKOpOHOByiO KMCHOTy M β-ļ _4 Γ71Κ)Κ033ΜΜΗ C Μ3ΜΘΗΑΙ01ΜΜΜ051 οτΗοιυβΗΜβΜ κομποηθητοβ: ee MoneKyrmpHbiM Bec HaxoqMTCfl b npeqenax ot 50 Tbic. qo HecKonbKMx (ot 8 qo 13) μπη. 06Hapy>KeHMe rManypoHOBoii κμοποτη -CTapaa 3aqaHa; BbipeneHMe μ πρΜΜβΗβΗΜβ οβθρχημοτομ rManypoHOBOM κμοποτμ paccMaTpMBaeTca β οπμοθημμ Μ3θ6ρβτβΗΜΑ κ naTeHTaM ClilA N 4141973 m 4303676 μ β βΒροπβίίοκοΜ οπμο3ημμ Μ3θ6ρβτβΗΜΑ κ naTeHTaM N 0144019. Jļo nocnepHero ΒρβΜβΗΜ rManypOHOByio KMcnoTy Mcnonb30BanM b BMqe ΗβτρΜβΒοίί οοπμ, HanpMMep. b TepanMM, rnaBHbiM o6pa30M, b o0TanbMonorMM, xMpyprMM m κοοΜβτοποΓΜΜ. Οοπμ γμθπυροηοβομ KMcnoTbi, coqep>KamMe MOHbi menoHHbix m menoHH03eMenbHbix μθτθπποβ, μθγημβ, θπιομμημβ, θμμοημ* μπμ npoM3BoqHbix aMMOHMfl, ΜΟΓγτ 6biTb ncnonb3oeaHbi b KanecTBe HoenTenen, npoMOTnpy»omnx a6cop6pwo neKapcTB (cm. onncaHne n306peTeHna k naieHTy Eenbrnn N 904547). Conn T«>Kenbix MeTannoB rnanypOHOBon KncnoTbi (b κοτορ^χ κ ”Tax<enbiM MeTannau’ OTHOcaT θπθμθητν 5, 6 n 7-oro nepnopoB nepnopnHecKon Tačnnpbi, a TaiOKe nam-aHnpbi n aKTnHnpbi) n conn cepeāpa βμθοτθ c hmmm ncnonb3yiOT b KasecTBe 0yHrnunflHbix BemecTB, Torpa xax conu 3onoTa πρηΜΘΗΒίοτ pna neneHna apipuTa (cm. onncaHne n3o6peTeHna k naTeHTy WO 87/05517).
Bbino flOKa3aHO nyieM ncnonb30BaHna pa3nnHHbix cnocočoB oābacHeHna CTpyKTypbi, hto BTopnHHaa CTpyKTypa, t. e. κοΗφορΜθρηΒ rnanypoHOBon KncnoTbi ηθμθηβθτοβ nocpepcTBOM coepnHeHna mohob μθτθπποβ (W. T. VVinter and A. Srutter: J. Mol. Biol. 517, 761 (1977), Y. K. Sheehan and E.D.T. Atkins: Int. J. Biol. Macromol. 5, 215 (1983) and N. Figueroa and B. Chakrabarti: Biopolymers 17, 2415 (1978)). 3HaHmenbHoe μ3μθηθημθ MoneKynapHon CTpyiaypbi7 xax noxa3biBaeT cpaBHmenbHoe ρθητγθηοβοκοθ nccnepoBaHne rnanypoHaTOB Kanna n HaTpna. μοχθτ 6wTb Bbi3BaH0 pa>κθ noHaMn nopo6Hbix MeiannoB (A. K. Mitra et al.: J. Macromol. Sci. Phys. 824, 1 n 21 (1985)). B nnTepaType Henb3a HaiiTn HHKaxnx ccbinoK, OTHocamnxca κ accopnaTaM (KOMnneKcaM) rnanypoHOBon KncnoTbi, copep^amen noHbi 3d MeTannoB ηθτβθρτογο nepnopa nepnopnnecKon Ta6nnpbi. flencTBnTenbHO, b οοοτβθτοτβμμ c paHHbiMn xpoMaTorpa$nHecKoro aHann3a npn cpnnbTpapnn rēna, rnanypoHOBaa KncnoTa ηθ μο>κθτ CBa3biBaTb noHbi pnHKa, b omnnne ot renapnHa (R. F. Parrish and W. R. Fair: Biochem. J. 193, 407-4010 (1981)).
HecMOTpa Ha tot $aKT, hto b οοοτβθτοτβηη c nniepaTypHbiMn paHHbiMn rnanypoHOBaa KncnoTa (nnn ee HaTpneeaa conb) ηθ μο>κθτ CBa3bieaTb noHbi pnHKa, aBTopbi HacToaipero n3o6peieHna pernann 3apany nccnepoBaTb xnMnnecKne npopeccbi B3anMopeiicTBna Mexpy rnanypoHOBon κηοποτοίί n noHaMn 3d MeiannoB ηθτβθρτογο nepnopa nepnopnnecKon Tačnnpbi, BKmonaiomen b ceča rnaBHbiM o6pa30M noHbi pnHKa n KoCanbTa. TaK KaK b npoMbiiuneHHOM npon3BopcTBe rnanypoHOBy»o KncnoTy BbinycKaK)T npaKTnnecKn TonbKO b Bnpe ee ΗθτρηβΒοη conn, paHHaa conb aenaeTca οοηοβημμ βθιρθοτβομ, copepx<atpnM rnanypOHaT. ll03T0My nccnepoeaHna Hanann c n3yneHna npopecca B3anM0peiicTBna noHOB HaTpna n rnanypoHaTa. C 3τοη penbīo aKTnBHOCTb ceo6opHbix noHOB HaTpna n3 βορηνχ pacTBopoB rnanypOHaTa HaTpna 6bina onpepeneHa c noMoīpbio CTeKnaHHoro HaTpnn-ceneKTnBHoro aneKTpopa. B cooTBeTCTBnn c paHHbiMn nccnepoBaHnn 6bino 0PH03HaHH0 ycTaHOBneHO. hto ηθ 6onee. ηθμ 60% hohob HaTpna. ββθρθηηηχ b 3KBnBaneHTH0M cooTHOiueHnn βμθοτθ c Kap6oKcnnaTHbiMn rpynnaMn manypoHaTa, npncyTCTByioT b BopHbix pacTBOpax b Bnpe CBo6opHbix noHOB, Torpa κβκ ocTaBLuneca 40% o6pa3yioT CBa3b LV 10965 c rnanypOHaTOM. B ΟΟΟΤΒΘΤΟΤΒΜΜ C Μ3ΜΘΡΘΗΜΒΜΜ 6blHO ΟΠρβΡΘΠΘΗΟ, ΗΤΟ ΠγΤΘΜ γΒΘΠΜΗΘΗΜΗ KOHUeHTpaumi MOHOB HaTpua, ΚΟΠΜΗΘΟΤΒΟ ΧΜΜΜΗΘΟΚΜ CBB3aHHblX HOHOB HaTpMB μο>κθτ 6biTb υβθπμηθηο flo 50-55% b pacneTe Ha Bce KapčoKCM/iaTHbie rpynnbi. TaKMM o6pa30M, 6bino BbiaeneHO, hto ηθομοτρ* Ha oāiuMe xapaKTepncTMKn Bcex οοπθμ, rnanypoHaT HaTpMB ηθ nonHOCTbio αμοοορμμρυθτ b boahom pacTBope.
Ha cnenyioiueM CTapMM MceneflOBaHMM BOflHbiM pacTBop rnanypoHaia HaTpMH 6bin OTTMTpOBaH paCTBOpOM Xnopnna UHHKa ΓφΜ MCn0nb30BaHMM HaTpneBOrO moh—οθπθκτμβηογο aneKTpooa, ynoMiiHyToro Bbiiue npH onncaHnn οπρθοθπθημη Μ3ΜΘΗΘΗΜΒ aKTMBHOCTM CB060flHblX MOHOB Η3ΤρΜΒ B ΟΜΟΤΘΜΘ. Χ3ρ3ΚΤθρΜ0ΤΜΗΘ0Κ3Β
KpMBajļ, onMCbiBaHDinafl npouecc, npepcTaBneHa Ha pMc. 1. Ποηβτηο, ητο
ΧΜΜΜΗΘΟΚΜ CBB3aHHbie C ΓΜ3Πγρ0Η3Τ0Μ MOHbl ΗΟΤρΜΒ ΟΟΒΟδΟΧφΟΙΟΤΟΒ ΠΟΑ ΠΘΜΟΤΒΜΘΜ MOHOB
UMHKa. B ΟΟΟΤΒΘΤΟΤΒΜΜ C pe3y/lbTaTaMM Μ3ΜβρΘΗΜΜ 06maa KOHUeHTpaUMB MOHOB
HaTpMB ocBo6o>KnaeTCfl 3a οηθτ θκβμββπθητηογο κοπμηθοτβθ umhkb - φθκτ, onpeneneHHO noKa3biBaioinMM, ητο MOHbi UMHKa o6pa3yioT c TManypoHaTOM 6onee npOHHyiO CBfl3b, ΗΘΜ MOHbl ΗΒΤρΜΒ. TaKMM 06pa30M, 60ΠΘΘ paHHee γΤΒθρΧφθΗΜΘ 0 tom, hto rManypoHOBaa κμοποτβ ηθ μο>κθτ CBB3biBaTb MOHbi UMHKa (R. F.Parrish and W. R. Fair: Biochem. J. 193, 407 (1981)) 6bino 3KcnepMMeHTaribH0 onpOBepmyTO. B ΟΟΟΤΒΘΤΟΤΒΜΜ C flaHHbIMM ΠρΟΒΘΑΘΗΗΜΧ MCCneflOBaHMM CTaHOBMTCB BCHO, HTO 6naroaapa β33μμορθμοτβμιο 3KBMBaneHTHbix κοπμηθοτβ TManypOHaTa HaTpMB m mohob UMHKa (xnopMfla UMHKa) b BopHOM pacTBope, o6pa3yeTCfl accouMaT TManypoHaTa umhkb οτθχμομθτρμηθοκογο cocTaBa. Ποοπθ οοοτβθτοτβυιοιιιθμ M30T0HM3auMM ποπυηθηημμ pacTBop μο>κθτ ηθποορθποτβθηηο Mcnonb30BaTbca b TepaneBTMHecKMx uenflx. μ οοθαμηθημθ umhkb b τβθρρομ coctobhmm ηθ hy>kho nonynaTb OTnenbHbiM cnocoOoM. OcymecTBneHMe npenBapMTenbHbix μοοπθποβθημμ C ΠρΜΜΘΗΘΗΜΘΜ MOHOB KOČa/lbTa M flpyTMX MOHOB 3d ΜΘΤΘΠΠΟΒ npMBOflMT K aHanorMHHbiM pe3ynbTaTaM. Ēbin ΠΟΠγΗΘΗ ΚΟΜΠΠΘΚΟ B TBepflOM COCTOBHMM flJlfl M3yHeHMfl CBOMCTB ΟΟΘΟΜΗΘΗΜΒ, Μ ΗΘΠΟΟρθΑΟΤΒΘΗΗΟΘ ΟΚργ>ΚΘΗΜΘ MOHOB UMHKa 6binO ΜΟΟΠΘΡΟΒβΗΟ ΜΘΤΟΗΟΜ ΠΟΠγΗΘΗΜΒ ΤΟΗΚΜΧ CTpyKTyp ΠρΜ ΠΟΓΠΟΙΜΘΗΜΜ ρθΗΤΓΘΗΟΒΟΚΜΧ ΠγΗΘΜ.
Bbino ycTaHOBneHO, ητο umhk οκργ>κθΗ neTbipbMB aTOMaMM yrnepona βο ΒΗγτρθΗΗΘΜ KOOpflMHaUMOHHOM Οφθρθ. flHMHa CBB3M Ζπ-0 paBHa 199 ρΜ, TOTfla KaK flBa aTOMa yrnepona HaxoflHTca Ha paccTOflHMM 241 pM ot aTOMa umhk3. B ΟΟΟΤΒΘΤΟΤΒΜΜ C ΜΟΟΠΘΠΟΒ3ΗΜΒΜΜ TManypOHaT UMHKa 3HaHMTenbHO 0ΤΠΜΗ3ΘΤ0Β ot aHanorMHHoro KOMnneKca μθπμ. KOTopbiii conep>KMT neTbīpe SKBaTOpMaribHbie m flBe OCeBbie CBH3M Cu-0 Τ1ΠΜΗΟΜ 194 M 234 PM ΟΟΟΤΒΘΤΟΤΒΘΗΗΟ. PaCCTOBHMe 4
Mex<my aTOMOM Meqn μ qByMH yrneBoqopoqHbiMM aTOMaMu paBHo 258 pM. CīpyKTypa KOMnneKca KoSanbTa nopoČHa CTpyKType κομππθκοθ unHKa, a ηθ Meqn. M3o6peieHne, TaKMM o6pa30M, KacaeTca KOMno3nunii, coqepx<aiuMX b ιοηθοτβθ aKTMBHOrO Κ0ΜΠ0ΗβΗΤ3 ΜΠΜ ΗΟΟΜΤΘΠΒ aCCOUMaT (ΚΟΜΠΠΘΚΟ) rnanypOHOBOM KUCHOTbl c MOHaMM 3d MeTanna ηθτβθρτογο nepnopa nepnopunecKOM Ta6nm_ļbi Heo6fl3aTenbHO b cocTaBe c qpyrnMM aKTUBHbiMM κομποηθητθμμ n/nnn poSaBKaMn.
Bxoflyunne b cociaB κομπο3ιίι4Ιίμ κομππθκομ nonyHatOT cneqytoiqnM o6pa30M: a) ūoāaBneHne βοηηογο pacTBopa, coqep>KaLuero 3κβμβ3πθητηοθ κοπμηθοτβο conn, npeflnoHTUTeribHO xnopnqa ορηογο M3 mohob 3d MeTanna ηθτβθρτογο nepnoqa nepnoqnHecKOii Taānmjbi, b BOflHbiiži pacTBop rnanypoHaTa HaTpun μπμ qpyroM conu (conu menoHHoro nnn inenoHH03eMenbHoro MeTanna, npn >xenaHMM, conu cepebpa) rnanypoHaTa, nnn
b) pacTBopeHne accoqnaTa, o6pa30BaHHoro M3 rnanypoHaTa KucnoTbi βμθοτθ c conbīo ΗβτΒΘρτΜΗΗΟΓΟ aMMOHMfl b BOflHOM cycneH3MM, b ομθομ pacTBopnTeneii, coqep)KaiHMX BOflHbie pacTBopbi 3d MeTanna ηθτβθρτογο nepnoqa πθρμορμηθοκομ Taānuubi n pacTBopuTenb, ηθοτμηηο CMeujMBaeMbiM c BoqoPi, πρθαποητμτθπβηο H-6yTaHon, 3aTeM - oca>KiļeHMe accounaTa (KOMnneKca), nonyneHHoro M3 rnanypoHOBoii KucnoTbi c hohom 3d MeTanna ηθτβθρτογο nepnoqa nepnopunecKOM Ta6nnubi, μ3βθοτημμ cnocočoM c πρνίΜΘΗΘΗΜΘΜ anKaHona nnn anKaHOHa, μπμ - BbiqeneHne ocaqKa H3 pacTBopa m 3aTeM, npn >KenaHnn, - BbicyuiHBaHne b μβγκμχ ycnoBnax. B npouecce nonyHeHMfl accounaTOB MeTannoB cnocočoM, yKa3aHHbiM Bbime, pH ocTaeTca paBHbiM 5. B cnynae 0,2 βθο./ο6.% pacTBopa rnanypoHaTa, pH qocTnraeT BennHMHbi 5,4, Torqa xax b cnynae 0,5 βθο./ο6.% pacTBopa, pH paBHo 5. flpM Heo5xoqnMOCTM, pH ποοπθρηθγο pacTBopa μοχηο ροβθοτμ ot 5,5 qo 5,6 nyTeM qo6aBneHMfl ηθοκοπβκμχ Kanenb μθοτοημηθοκογο pacTBopa aueTaTa HaTpua.
PacTBOpbi qByx bupob. copepacauuie rnanypoHaT UHHKa b κθηθοτβθ 3κτμβηογο κομποηθητ3, MoryT 6biTb nonyneHbi cnocoāoM, yKa3aHHbiM Bbime. H30T0HMHecKnii pacTBop rnanypoHaTa UMHKa nonyHaiOT nyTeM qo6aBneHna M36biTKa xnopnqa uMHKa. C yneTOM τογο, hto CBo6oqHbiii xnopnq UHHKa μο>κθτ 6biTb ncnonb30BaH b qepMaTonormi, οομοτμηθοκοθ ρθβπθημθ pacTBopa rnanypOHaTa uhhio 6bino qoeeqeHO qo μ30τοημηθοκογο qaBneHna c noMombio xnopnqa unHKa. PacTBop, nonyHeHHbiii t3kmm o6pa30M, ηθ coqep>KMT cBo6oqHbiii (ηθ CBH3aHHbiM c umhkom) rnanypoHaT Booāme, ho b ομομθμθ βμθοτθ c raanypOHaTOM UHHKa npncyTCTByeT M36biTOK xnopnqa UHHKa. 2. l/l30T0HHHecKnvi pacTBop rnanypoHaTa UHHKa nonyna»OT nyTeM qo6aBneHna LV 10965 MOHOcaxapnfla μπμ caxapHoro crmpTa. Jļnn TepaneBTMMecKnx ueneii, Korpa npncyTCTBne mohob qnHKa, ηθ cBa3aHHbix c rnanypoHaTOM. ηθ oroBapMBaeTcn, μ30τοημηθοκμμ pacTBop, copep>Kaiunii HOHbi UMHKa B ΚΟΠΜΗΘΟΤΒΘ, 3ΚΒΜΒ3ΠΘΗΤΗ0Μ rnanypOHaTy, nOnyHaKDT C ΠρΜΜΘΗΘΗΜΘΜ MHoroaTOMHoro criMpTa (caxapHoro cnnpia, npeMMymecTBeHHo copāmona) μπμ moho— Unu ancaxapnjqa (npenMymecTBeHHO rmoK03bi). Copep>KaHne cbočophoio MOHa LļMHKa h CBo6opHoro manypoHaTa b paHHoii ομοτθμθ ηθ pocTMraeT 5% ot oOiuero copepaoHMn unHKa v\m rnanypoHaTa, θοοτβθτθτβθηηο. B npopecce ncnonb30BaHna accoqnaTOB b οοοτβθτοτβμμ c Μ3ο6ρθτθημθμ co βρθμθηθμ MoryT noHapo6wTbcn οοθρμηθημη, cojqepx<aiyne CBoāopHbie HOHbi. To ecTb accouMaTbi, nonyneHHbie cnocoOoM, yKa3aHHbiM Bbiiue, oābiHHo copep>KaT xnopnp HaTpMH μπμ ppyryio conb, o6pa30BaHHyKD H3 KaTHOHa ncxonHoro rnanypoHaTa μ aHMOHa conn 3d MeTanna. flea pa3nMHHbix BapMaHTa cnoco6a MoryT 6biTb ncnonb30BaHbi pnn nonyHeHHii accouMaTa rnanypoHOBoii KMcnoTbi, ηθ coaep>Kamero conb, o6pa30BaHHoro c noMoiubfo HOHa 3d MeTanna. 3to ocymecTBnneTcn cnepyK>mnM o6pa30M. a) PacTBop conn μθτβθρτηηηογο aMMOHvm nopuHOHHO počaBnaioT b M3BecTHbiw pacTBop rnanypoHaia, npepnoHTMTenbHO rnanypoHaia HaTpmi. ilocne ohmctkm HOBbiPi ocax<fleHHbiM accoqnaT conn ηθτβθρτμμηογο θμμοημα pacTBopfltOT npn MHTeHCMBHOM nepeMeiiiHBaHMM b cMecH pByx pacTBopmeneii, cocTonmnx M3 βορηογο pacTBopa HOHa 3d MeTanna ηθτβθρτογο nepnopa πθρμορμηθοκομ Taānmjbi n pacTBopuTena, MacTvmHo CMeiuviBaioinerocn c boqom, npepnoHTHTenbHO H-6yTaHona. flBe cpa3bi mo>kho pa3pennTb, 3aTeM accoqnaT rnanypoHaTa ocax<naiOT nyTeM počaBneHHH anKaHona mv\ anKaHOHa b BopHyio cf>a3y. OcapoK OTpennKDT h npoMbiBaiOT, μπμ b) Ilocne počaBneHMfl ot 2,0 po 3,0 ο6τ>θμοβ C-|_3 anKaHona Unu Οβ_4 anKaHOHa npw nepeMeuuHBaHHH κ pacTBopy rnanypoHaTa qnHKa, cooTBeTCTByioipeMy HeM30T0HM3np0BaHH0My pacTBopy, copep>KaLneMy xnopnp qnHKa, b κοπμηθοτβθ. SKBMBaneHTHOM rnanypoHaTy, ocaxpeHHbiii rnanypoHaT qnHxa OTc£>nnbTpoBbiBaiOT m npOMbiBaroT c noMombio anKaHona Unu anKaHOHa, οοοτβθτοτβθηηο ncnonb30BaHHOMy pnn ocax<peHnn. ripu ηθο6χορμμοοτμ, rnanypoHaT qnHKa pacTBopnioT b cboOophom βορθ v\ ποετορηιοτ npoqecc oca>KpeHMn.
Korpa ηθο6χορμμο nonynnTb TBeppbin rwanypoHaT qnHKa, copepacainHH CBoāopHbie HOHbi, ocapoK BbicyiiiMBaiOT noppaBneHMeM b μηγκμχ ycnoBnnx. B cnynae. eonn Tpe6yeTcn pacTBop rnanypoHaTa qnHKa. copepx<aipnH cBoOopHbie MOHbi, npepnoHTMTenbHO pacTBopHTb rnanypoHaT qnHKa, nonyHeHHbiPi H3 pacTBopHTenn. B οοοτβθτοτβμμ c mo6biM M3 o6ohx BapnaHTOB npoqecca TBeppoe r> μπιί pacTBopeHHoe βθικθοτβο, copep>Kamee CBo6opHbie MOHbi, nonyHaK)T c np0M3B0nbH0M HMCTOTOM, 33ΒΜ0ΗΙΡΘΜ OT Κ3ΗΘ0ΤΒ3 ΜΟΧΟΡΗΟΓΟ rManypOHaTa IļMHKa.
Pe3ynbTaTbi κπμημκο—Φθρμθκοπογμηθοκμχ MccneflOBaHuii οοθριίηθημβ (npmviep 13), copepacauuero b ιοηθοτβθ θκτμβηογο κομποηθητθ rnanypoHaT LiMHKa b ΟΟΟΤΒΘΤΟΤΒΜΜ C Μ3θ6ρθΤΘΗΜΘΜ, ΠΟΗΟΗΗΙΟΤΟΗ Ha ΠρίΊΜθρθ ΠΘΗΘΗΜΗ 6θΡΡΘΗΗθίί B3Bbl npM MCnonb30BaHMM ΟΟΘΡΜΗΘΗΜΗ ΡΠΗ 3ΠΜΤΘΠΜ3ΘΙ4νΐΜ ΠΟΒθρΧΗΟΟΤθίί Tena, nmueHHbix anuTenna. Οοθρμηθημθ, copepacaiuee rnanypoHaT ηθτρμη, 6bino ncnonb30BaHO b ιοηθοτβθ KOHTponbHoro o6pa3pa.
HacTOHmee μοοπθροβθημθ 6bino προβθρθηο Ha 12 hhm 14 o6pa3uax οοοτβθτοτβθηηο, c noMombto 8-12 nauneHTOB, cTpapatoiqnx 6eppeHHoii b3bom. PacnpepeneHHe nauneHTOB o6ewx rpynn b οοοτβθτοτβμμ c ποπομ m B03pacT0M, a Taoce npupopoti 6οπθ3ημ 6bino cnepyiomwM.
AlCTMBHblM ΚΟΜΠΟΗΘΗΤ N napHeH- Ta >Κθη- LUMHbl My>K- HMHbl Cpejņ-h m B03paCT N Bbine- HeHHblX XapaxTep s33Bbi * A V M rnanypo-HaTUMHKa 12 10 2 69,9 14 2 9 1 Tnanypo-HaT HaTpua 8 6 2 65,7 12 - 7 1 * A - apTepnanbHaat V - βθηοθηθη, M - cMemaHHaa
Jleηθημθ 6bino npeayCMOTpeHO tskum o6pa30M, hto npeflBapmenbHO npoBOflHnacb TepaneBTMHecKasi o6pa6oTxa b οοοτβθτοτβμμ c κπμημηθοκμμ οοοτοηημθμ B3Bbi. Πθηθημθ c noMOUļbK) TManypoHaTa umhio μπμ ηθτρμη, οοοτβθτοτβθηηο, 6bino HanaTo Ha o6pa6oTaHHbix «3Bax μπμ B3Bax co 3HanMTenbH0 coKpameHHbiMH py6uaMM. Πθηθημθ npoBopMnocb θ>κθρηθβηο τθκμμ o6pa30M, hto ormh pa3 b qeHb Ha noBepxHOCTb, nopa>KeHHyto π3βομ, ηθηοομποη tohkmm οποίί CMaHMBaioiuero paHy neKapcTBa. Οοθρμηθημθ ncnonb30Banocb b τθηθημθ neTbipex Hepenb. B Hanane πθηθημη m 3aTeM pa3 b ηθρθπιο 38ποπηβποπ πμοτοκ 3anncn pe3ynbTaT0B πθηθημη m penanMCb Φοτοοημμκμ ynacTKOB ko>km nauHeHTa, nopax<eHHbie Η3Βθίί. ΠροεορΜποπ 6aKTepnononiHecKnii aHann3 o6pa3pa.
XapaKTepncTMKM m cTeneHb nopax<eHMfl 3πμτθπμπ 6bmn οτμθηθημ c noMombio HM>KecnepyK)iunx o6o3HaneHMM h 3annceii.
XapaKTepncTMKM CTeneHb nopa>KeHH3 7 LV 10965 ΥΗβοτοκ (a) 0 0 Μθηθθ 10 cm2 1
Mex<ny 10 m 25 cm2 2
Bonee 25 cm2 3 l/lHCpMUMpOBaHHOCTb (b) Κ/ΙΜΗΜΗΘΟΚΜ HMCTbIM 0 noKpbiTbiPi Ha 50% 1 lloKpbiTbiii Ha 100% 2 ΗΘκρο3 (c) (TonbKo b cnynae apTepnaribHOM fl3Bbl) OTpmjaTenbHbiii 0
Hn>Ke 10% 1
Mexny 10 h 15% 2 100% 3 OTcyrcTBne HeKpQ3a_4
OueHKa flna oueHKH 6binn onpeneneHbi θηθηθημα omenbHbix xapaKTepncTHK m očmaa CTeneHb nopa>xeHH5ļ 6bina paenmaHa c noMombio cnenyioLneM cpopMynbi: S = yļaxbxc
Pe3ynbTaTbi κπμημκο—Φ3ρμ3κοπογμηθοκμχ μοοπθοοβθημμ nnntocTpnpyK)Tcyi Ha pHC. 2. Pe3yribTaTbi πθηθημα c noMotpbio rnanypoHaTa UHHKa noKa3aHbi Ha kpmbom, οτμθηθηηομ KpecTHKaMM, a c noMouļbio rnanypoHaTa Haipn5ļ - Ha kpmbom,
ΟΤΜΘΗΘΗΗΟΜ ΚΒ30ρθΤΜΚ3ΜΜ, KaK (f)yHKUMM OT HMCna Hepenb, B ΤΘΗΘΗΜΘ KOTOpblX npoBOflnnocb πθηθημθ. BenHHHHa οτθπθημ nopax<eHna noKa3aHa Ha οραμηθτθ, npeacTaBrmromeii co6om očiumm noKa3aTenb nopax<aHMfl, paccHMTbiBaeMbiM no yKa3aHHoii Bbiiue cpopMyne. fln* 6onee npaBMnbHoro cpaBHeHM?i manypoHaTa Haipna n rnanypoHaTa UMHKa Ha pnc. 3 npMBOAaTca oTHOCMTenbHbie θηθηθημη οτθπθημ nopaweHMfl npu 100% ΟΟΟΤΗΟΙΙΙΘΗΜΜ C MCXOAHblMM 3Η3ΗΘΗΜ3ΜΜ ΟΤΘΠΘΗΜ nOpa>KeHMfl. Ι/Ι3ΜΘΗΘΗΜΘ OTHOCMTenbHblX 3Η3ΗΘΗΜΜ 6binO ΟΤΘΤΜΟΤΜΗΘΟΚΜ ΟΜΘΗΘΗΟ ΚΘΚ <ļ>yHKUMa οτ HMcna (οτ 1 ρο 4) Heaenb. ΠρΜ πθηθημμ c noMombio rnanypoHaTa UHHKa μ manypoHaTa HaTpiia 6bino μοοπθαοβθηο hmcjio h3b, yMeHbWMBWMxc5ļ flo 90%, 80%, 70% m 60% οτ OTHOcirrenbHoro 3Η3ηθημ?ι οτθπθημ nopax<eHMSļ nocne 1, 2, 3 m 4-x Heflerib. οοοτβθτοτβθηηο. Pe3ynbTaTbi cyMMMpoBaHbi b Ta6nnqe 1.
TačnMua 1. 8 1-flHenerm 2-a Hepena 3-a Hepena 4-a Hepena AKTMBHbiii PacnpocTpaHeHne OTHOCMTenbHoro 3HaHeHMa οτθπθημ nopax<eHMa ΚΟΜΠΟΗΘΗΤ 90% 80% 70% 60% ΗΜ>ΚΘ Bbiuie ΗΜΧΘ Bbiiue ΗΜΧΘ Bbiuie ΗΜ)ΚΘ Bbiiue Γ Manypo-H3T UMHKa 12 2 11 3 11 3 11 3 Γ Manypo- 4 8 7 5 6 6 3 9
HaT HaTpna B οοοτβθτοτβμμ c naHHbiMM TačnuMbi 1 μο>κθτ 6biTb ycTaHOBneHo, ητο πθηθημθ c noMombto ruanypoHaTa UMHKa Ka>Kpyio ηθρθπιο 6bino 6onee θΦΦθκτμβηο no cpaBHeHMK) c pe3ynbTaTaMM, nonyneHHbiMM πριι πομοιρμ rnanypoHaTa HaTpMa, ncnonb3yeMoro b KaaecTBe KOHTponbHoro BeipecTBa. CTaTMCTMHecKuii aHariM3 nonyseHHbix paHHbix noKa3an, hto npewviymecTBO οοθρμηθημ3 rnanypoHaTa UMHKa ābino 3HanMTenbHbiM (p. 99%) no ορθβηθημιο c rnanypoHaTOM HaTpMa. npn aanbHeiiiuMx οτθτμοτμηθοκμχ pa3pa60TKax 6bino MccnepoBaHo 6onee noapočHoe pacnpeneneHne OTHOcmenbHbix θηθηθημμ οτθπθημ nopa>KeHMH xax φyHK^M^1 ΒρθΜΘΗΜ πθηθημλ. Πογ^ηθηημθ pe3ynbTaTbi cyMMnpoBaHbi b Ta6nnue 2.
Ta6nMua 2. Ημοπο m 3HaneHMe οτθπθημ nopaaceHMa AKTMBHblii ΚΟΜΠΟΗΘΗΤ A3B0M BblLUe 90% ΜΘΧαΥ 90 Me>Kfly 70 ΗΜ>ΚΘ _00ΘΡΜΗΘΗΜ3_50% Μ 70% Μ 50%_ 1-51 ΗΘΠΘΠΗ
ΓManypoHaT UMHKa 2 7 5 0 Γ ManypoHaT HaTpMa 8 3 0 1 2-a Hepena TManypoHaT UMHKa 0 6 7 1 ΓManypoHaT HaTpMa 4 > 5 0 3-a Hepena ΓManypoHaT UMHKa 0 1 8 2 ΓManypoHaT HaTpMa 2 5 5 1 4-51 ΗΘΡΘΠη ΓManypoHaT UMHKa 2 1 7 Λ J ΓManypoHaT HaTpMa 1 5 J Λ J JļaHHbie Ta6nMLjbi 2 το>κθ nopTBep>xpaioT npeMMyipecTBo Mcnonb30BaHMa 9 LV 10965 rnanypoHaTa um-iKa. Bonee nonpočHbie CTaTMCTunecKue nccneflOBaHua yi<a3biBai0T Ha 3HaHmenbHoe yMeHbweHne οτθπθημ nopax<eHMn, 3aBMcnmee οτ βρθμθημ πθμθημη.
BbiBop: ripu ομθηκθ κπμημκο-Φβρμβκοπογμηθοκμχ McenenoBaHMii BbicoKaa aKTMBHocTb rnanypoHaTa LļMHKa μο>κθτ 6biTb noKa3aHa na?Ke Ha npmviepe HečonbLuoro HHcna b3b; sto npemviyinecTBO μοχθτ 6biTb οοο6θηηο Bbipax<eHo Ha HaHanbHoii CTaann πθηθημπ. l/l3oāpeTeHne 6onee ποηροδΗο nnmocTpnpyeTCfl HM>KecnenyioinMMM HeorpaHHHeHHbiMM npmviepaMH.
Coqep>KaHMe npoTeMHa b rnanypoHaTe (HA) 6bino onpeneneHO μθτοαομ Ο. H. Lowry (J. Biol. Chem. 193 (1951)), BH3K0CTb rnanypoHaia 6bina M3MepeHa BMCK03WVieTp0M OCTBanfla B φΜ3110Π0ΓΜΗΘ0Κ0Μ ΟΟΠΗΗΟΜ paCTBOpe ΠρΜ 25°C. 3η3ηθημθ xapaKTepncTMHecKOM βπ3κοοτμ, SKCTpanoni/ipoBaHHoe no ”0” KOHueHTpauMM, t. e. [η] c -» 0%, npneeneHO ημ>κθ. Conep>KaHMe HA 6bino onpepeneHO μθτοηομ Brnrepa (Anal. Biochem. 4, 330 (1962)). flpHMep 1 ΠρκΓοτοΒΠΘΗΜθ pacTBopa rnanypoHaia UMHKa. 40,18 μγ rnanypoHaTa ηβτρμβ pacTBopaioT b 20,0 μπ nea>Knbi flncTnnnnpoBaHHOM Boqbi. TaKMM o6pa30M. ncxoflHaa KOHueHTpauMH rnanypoHOBoii KHcnoTbi cocTaBnaeT 2,009 μγ/μπ, 3κβμβ3πθητη33 KOHueHTpai4na pacTBopa - 4,241 x 10-3 Monb/nmp (Na+ nmi amviep rnanypoHOBon KHcnoTbi). B xone n3MepeHMii pacTBop xnopnna uhhkb KOHuempamieM 0.05154 Monb/nnTp noāaBnaioT b peaKUMOHHyio CMecb nepe3 MMKpo6rapeTKy. CHanana pacTBop nočaBnaioT ManeHbKMMM nopuMHMM (0,05 μπ), a 3aieM 6oribiunMn (ot 0,1 no 0,2 μπ). H3MeHeHne noTeHunana pacTBopa H3MepflK)T c noMombio τοηηογο noTeHUHOMeipa c ΜΜφροΒοΡί HHnMKauMeii, HaTpneBoro hoh— ceneKTHBHoro οτθκππηηογο sneKTpona h cepečpnHoro sneicrpona. THTpoBaHMe προηοπχοιοτ no τβχ nop, noKa n3MepneMbiH noTeHLļHan ηθ 6yneT M3MeHflTbCfl npH nočaBneHHM cnenyiOLueM nopunn pacTBopa nna TMTpoBaHHfl (n3MepnienbHaa CMCTeMa 6bina OTKann6poBaHa b ycnoBnnx, aHanorMHHbix πρβκτμηθοκμμ MeTonaM M3MepeHnPi). M36npaTenbHoe πθηοτβμθ μοη-οθπθκτμβηογό sneicrpona Hačnionanocb τθιοκθ b npMcyrcTBMM hohob Zn2+ c uenbīo κοΗτροππ 3a μ3μθηθημθμ noTeHunana B npaKTHHecnx M3MepeHMnx, Bbi3BaHHbix HannmieM CBo5onHbix hohob Na+, ho He Zn2+, BBonnMbix b pacTBop. PacTBop xnopnna HaTpHH KOHueHTpauMeii 2,00 χ 10-2 M 6bin OTTHTpoBaH c noMouļbio pacTBopa xnopwna LjHHKa b ycnoBnnx, aHanornMHbix BblLJUeonHCaHHblM. ΠρΜ B03paCTaHMH KOHLieHTpaMHH Zn2+ OT 0 ΠΟ 4 X 10~3 Monb/nnTp ροοτ noTeHUHana cociaBHn 2 mB, Torņa xax npaKTHnecKHe M3MepeHnn b 10 aHanorMHHbix ycnoBM?ix noKa3ann μθμθηθημθ noTeHunana Ha 20 mB. TaKMM o6pa30M, oueHKa ηθ Bbi3biBaeT 3aTpyflHeHMM. B xoqe M3MepeHMii yβθπμηθημθ aKTMBHOCTM MOHOB HaTpMB, paCCMMTblBaeMOe Ha OCHOBe naHHblX Μ3ΜΘΡΘΗΜΜ, očHapy>KHBaeT κοπμηθοτβθηηοθ o6pa30BaHne accounaTa unHKa. ΠρΜΓΟΤΟΒΠΘΗΜΘ paCTBOpa xn0pnfla LļHHKa.
Tax Kax pacTBop, conepaoiuMii xnopnq 141/iHKa tohhom KOHLieHTpauHM, He μο>κθτ 6biTb nonyHeH HenocpencTBeHHbiM B3BeujnBaHneM, CHanana nonyHaioT pacTBop c npn6nn3HT0nbHO >xenaeMoii KOHueHTpauHeii. flnn πρμγοτοβπθημβ naHHoro pacTBopa ηθ Hy>KHO ncnonb30BaTb KMcnoTy, no3TOMy μοχθτ cnyHHTbCfl TaK, hto B3BeuunBaeMbiii xnopnq uMHKa 6yneT pacTBOpeH ηθ nonHocTbto. riocne ceflUMeHTauMu HepacTBopMMoro ocapKa (οκοπο 30 MMHyT) MepHyto xon6y HanonHBKDT no ΟΤΜΘΤΚΜ H pacTBop OTCpHnbTpOBblBaiOT Ηθρθ3 φHΠbTpOBaΠbHy^O 6yiviary.
ToHHyio KOHueHTpauHK) φΜΠΒτρ3τ3 onpenenaioT nyTeM κομππθκοομθτρμηθοκογο THTpoBaHHa c ncnonb30BaHneM 6yφepa 10 μ ηθρηογο T HHmHKaTOpa apnoxpoMa. PacTBop xnopnqa uMHKa tohhom KOHueHTpaunu 0,100 Monb/n nonyHaioT nyieM τοηηογο pa36aBneHMsi θτογο pacTBopa.
XapaKTepncTMKM rwanypoHaTa HaTpiiR ncnonb3yeMoro nna nonyHeHMfi pacTBopa:
MoneKynflpHbiti Bec: 1850000
Conep>KaHMe npoTeMHa: 0,07 Bec. % yO-ancop6una A"· ^257: 0,133 A1%280; ū'075
Ba3K0CTb [η] c -» 0% (25°C): 13,7 qn/r
Coqep>KaHMe HA*: 98,12 Bec % HA* = rnanypoHOBasļ KMcnota - /yKa3aHHoe Bbirne coKpameHne/ Πρμμθρ 2 nonyneHne pacTBopa nna αθρμθτοπογμηθοκμχ μ κοομθτοπογμηθοκμχ ueneii. 12.5 μπ pacTBopa xnopnqa UHHKa KOHuempaLiMeM 0.100 Monb/n, nonyweHHoro βμθοτθ co CBo6oqHoii boaom, no6aBna»OT κ 0.50 r B3BeiueHHoro rnanypoHaia b 100-ΜΠ MepHyio Kon6y (xnopnn uhhk3 qpyroii KOHueHTpaum/i μο>κθτ 6biTb ncnonb30BaH, ho ero κοπμηθοτβο flon>KHo ocTaBaTbcn npejKHMM). ΓnanypoHaT Haipnn Bbiqep>KMBaK)T qn« Ha6yxaHnn 12 nacoB b κοπόβ, ηθποπηθηηομ no οτμθτκμ CBo6onHOii βοπομ, c uenbīo nonyHeHnn pacTBopa rnanypoHaTa unHKa 0,5 Bec./o6. 11 LV 10965 0/ /0.
XapaKTepncTMKM rnanypoHaia Η3τρΐΊΗ, ncnonb3yeMoro prm nony4eHkin BbiujeyKa3aHHoro pacTBopa:
Bfl3K0CTb [η] c -> 0% (25°C): 16,5 qn/r Copep>KaHne npoienHa: 0,8 Bec. % ΠΡΜΜθρ 3 l1onyHeHne pacTBopa rnanypoHaia um-iKa nna ncnonb30BaHM5i b KanecTBe MH-beKLļMOHHoro pacTBopa. npouecc, onncaHHbiti b αεηηομ npMMepe αοπ>κθη 6biTb npoBepeH b CTepnnbHbix ycnoBnax. 0,5 ΜΠ pacTBopa xnopnna UMHKa KOHuempauMePi 0,100 Monb/n nony4aK)T βμθοτθ c flBax<fļbi flucTunnupoBaHHoii BonoPi (eopa nna MHbeKuuPi, nnporeHHbix npenapaTOB, CTepunbHaa) nočaBnatoT κ 0,20 r rnanypoHaia HaTpkm (b βμηθ ΗΜΟΤΟΓΟ nopOUJKa), Β3Β8ΐυθΗΗ0Γ0 B 100-ΜΠ ΜβρΗΟΜ ΚΟΠδβ. 33ΤΘΜ θ6ΐ»ΘΜ POBOflMTCfl fļBa>Kflbl PMCTunnupoBaHHoPi BOfloii no 50 μπ. Bcio HOHb rnanypoHaT HaTpua Bbinepx<MBaioT nna Ha6yxaHMH, 3aTeM pacTBopatoT npn BCTpflxnBaHnn n ποβοαατ pacTBop no otmbtkh flBa>Kflbi flMCTunnupoBaHHOM BOfloPi. flonyHeHHbiii pacTBop ΟΤφΐ/inbTpOBblBaiOT ΗΘΡΘ3 MeMČpaHHblM φΜ/lbTp (0,45 μ - pa3Mep nop) nna nony4eHUH 0,2 Bec./o6. % pacTBopa rwanypoHaTa UMHKa.
XapaKTepncTHKH rnanypoHaTa HaTpMH, ncnonb3yeivioro nna nonyHeHMfl BbiLueyKa3aHHoro pacTBopa:
KanecTBo: HMCTbiPi. CBOāoflHbiPi ot nnporem-ibix BemecTB CTepunbHbiM ποροιυοκ. MoneKyn?ipHbiM Bec: 1850000 Conep>KaHue npoTenHa: 0,07 Bec. % ΥΦ aOcopČL\v\9\ A"! %257; 0,133 A1%258: 0,075
Conep>KaHMe HA: 98,12 Bec %
Bsļ3K0CTb [η] c -> 0% (25°C) : 13,7 fln/r ΠρΜΜβρ 4 nonyHeHne pacTBopa rnanypoHaTa UHHKa co CBOčoflHbiMn MOHaMn. 600 μπ aTaHona nnn aHanMTMHecKMX ueneii aoOaBnatOT npn nepeMeujMBaHMM κ 200 μπ 0,50 Bec. % pacTBopa rnanypoHaia UMHKa, nonyHeHHoro b cooTBeTCTBun c npuMepoM 2. Oca>KfleHHbiPi rnanypoHaT pnHKa oτφ^1ΠbτpoBblBa^oτ Ha στβκππΗΗΟΜ φμπΒτρθ. flBa>Kflbi npoMbieaioT 50 μπ STaHona τογο >κβ «anecTBa m 3aieM BbicyiUMBaiOT npn noHM>xeHHOM naBneHMM. TaKMM o6pa30M, nony4aiOT 0,88 r rnanypoHaia unHKa, KOTopbiri ncnonb3y»OT qnn npnroTOBneHnn 0,50 Bec./ 06. % pacTBopa rnanypoHaTa 141/iHKa cnocočOM, yKa3aHHbiM b npuMepe 2. i1onyHeHHbiii pacTBop manypoHaTa UHHKa ηθ coqep>KHT xnopnq Haipnn, o6pa3yiOLUniicfl b pe3ynbTaie peaKunn Me*qy rnanypoHaTOM HaTpua η xnopnqoM unHKa: τβκμμ o6pa30M, oh cooepjKMT npaKTnnecKn CBoāoflHbie noHbi. Πρμμθρ 5 ΠοΓ^ΗΘΗΜθ rnanypoHaTa UHHKa cp CBo6oqHbiMn noHaMn nnn ero pacTBopa qnn TepaneBTMHecKMx ueneīi. ripouecc, onncaHHbiii b stom npuMepe, ocymecTBnnK>T b CTepnnbHbix ycnoBnnx. 1500 ΜΠ 3TaHona (BbicoKon HMCTOTbi) nopuMOHHO qo6aBn«ioT κ 500 μπ pacTBopa rnanypOHaTa uHHKa, nonyHeHHoro β οοοτβθτοτβμμ c npHMepoM 3 npn nepeMeiunBamiM. riocne qo6aBneHnn CMecb BCTpnxnBaiOT β τθμθημθ 30 MHHyT, oca>KfleHHbiii rnanypoHaT UHHKa OTCpMfībTpoBbiBaiOT Ha οτθκπηηηομ cJjnnbTpe, Tpn>Kflbi npOMbieaioT, ncnonb3ya qo 100 μπ STaHona (BbicoKon ημοτοτη) n BblCyiUMBatOT npM ΠΡΗΜΧΘΗΗΡΜ flaBneHMM B CTepnnbHblX H ΜΠΓΚΜΧ ycnOBM?ļX. IļpuMep 6 nonyHeHne rnanypoHaTa UHHKa co CBo6oqHbiMn μοηβμμ. 200 μπ 10 Bec. % pacTBopa rnaMMHa R-|g22 (6eH3nnqnMemn/-2-/2-p-(1,1,3,3-TeTpaMeTnn6yTMn)<$eHCKCM/3TOKCM/xnopnfl aMMOHnn) qo6aBnaK)T npn nepeMeiiiMBaHMM b pacTBop, coqep>KaLnnH 1 r rnanypoHaTa HaTpun b 400 μπ qea>Kqbi qncTnnnnpoBaHHOM Boqbi. 06pa30BaBiunncn ocaqoK, t. e. accounaT ηθτβθρτμηηογο aMMOHnn rnanypoHOBon κμοποτη BbiqenaK>T ueHTpnc}3yrnpoBaHneM, qBa>xqbi npOMbiBa»OT, ncnonb3yn no 100 μπ qncTnnnnpoBaHHon Boqbi h CHOBa ueHTpn0yrnpyK)T. npoMbiTbiii ocaqoK pacTBopniOT β CMecn pacTBopmeneH, cocTonmeii M3 400 μπ 2 Bec./o6. % xnopnqa UHHKa β bophom pacTBope (pH ot 5,0 qo 5,4) n 400 μπ H-6yTaHona. Ilocne Bbiqep>KHBaHnn qo o6pa30BaHnn qByx cpa3, BoqHbiii cnoii, coqep>KamMM pacTBopeHHbiii rnanypOHaT UHHKa OTCpnnbTpoBbiBaiOT nepe3 MeMāpaHHbiii cļ)nnbTp (0.45 μ - pa3Mep nopbi); 3aTeM rnanypoHaT unHKa ocax<qaK3T nyieM qo6aBneHnn τρβχ o6beMHbix nacien aTaHona, OTcpnnbTpoBbiBaioT Ha οτθκππηηομ cpHnbTpe, npoMbiBaiOT 3TaHonoM h BbicyiunBaK)T b aTMoc$epe a30Ta β μπγκμχ ycnoBnnx qo nonyHeHnn 0,82 r rnanypoHaTa unHKa. ripu Heo6xoqnMOCTM, 0.50 Bec./o6. % pacTBop nonynaK)T H3 nonyHeHHoro rnanypoHaTa uhhio. KOTopbin β qanbHenmeM onnmatOT cnocoSoM, yKa3aHHbiM b npuMepe 4.
XapaKTepncTHKn rnanypoHaia HaTpnn, ncnonb3yeMoro b KanecTBe ncxoqHoro LV 10965 π
BemecTBa:
Bfl3KOCTb [η] c -» 0% (25°C): 16,5 fln/r Coqep>KaHMe npoTenHa: 0,18 Bec./οδ. % ΓnanypoHaT unHKa μοχθτ 6biTb ποπγπΘΗ BbiiueyKa3aHHbiM cnocoāoM M3 accopMaTOB, o6pa30BaHHbix M3 npymx conefi ηθτβθρτμηηογο aMMOHMn. HeTBepTMHHbie conu, ηθο6χοημμμθ pna stom peņu: a) χποριιρ KapčoTeTpafleuMKnoKCMMeTMn-TpMMeTunaMMOHMM (cM.onncaHue Μ3θ6ρΘΤΘΗΜΑ κ naTeHTy Βθηγρμμ N 188537), b) xnopnfl reKcafleuunnMpMflMHa, c) xnopnfl ueTMnnupMflMHa, d) XHOpnn TpMMeTMnaMMOHM« M nOflOČHbie ΟΟΘΗΜΗΘΗΜΠ. ΠΡΜΜθρ 7 rionyMeHne rnanypoHaTa Ko6anbTa cooTBeTCTByeT cnoco6y, yKa3aHHOMy b npuMepe 6, 3a μοκπιοηθημθμ τογο, hto accopnaT rnanypoHOBoii κμοποτμ ΜΘΤΒΘρΤΜΜΗΟΓΟ aMMOHMfl paCTBOpBJOT Β ΟΜβΟΜ paCTBOpMTeneii, COCTOflUjeii m 2 Bec./o6. % xnopnpa KoSanbTa (II) 6H2O βοηηογο pacTBopa m H-6yTaHona. Πρμμθρ 8 f1onyHeHne βοηηογο pacTBopa, conep>Kainero 0,50 βθο./ο6. % rnanypoHaTa UMHKa, Μ Μ3ΟΤΟΗΜΜΘ0ΚΟΓΟ paCTBOpa C nOMOlUbK) XnOpMHa UMHKa. Οκοπο 50 μπ pacTBopa xnopMna pnHKa κοηρθητρθρμθμ 0,110 Monb/n Ho6aBnn»OT κ 0,50 r rnanypoHaia Haipna β 100-μπ MepHyio Kon6y m ocTaBnniOT Ha bcio HOHb ΗΠΒ Ha6yxaHMa. 3aTeM rnanypoHaT HaTpun pacrreopniOT npw BCTpnxMBaHMM m Kon6y 3anonH3K)T flo οτμθτκμ pacTBopoM xnopMfla unHKa KOHueHTpauMeii 0,110 Monb/n.
OcMOTMHecKoe naBneHMe nonyHeHHoro pacTBopa cocTaBnneT 0,1491 Monb/n, BenMHMHa pH paBHa 5,0. ΠρΜ ηθο6χοημμοοτμ BenMHMHy pH hobohhtho 5,5-5,6 nyTeM fločaBneHMH 2,00 μπ pacTBopa apeiaia ΗβτρΜΠ KOHueHTpauMeii 0,150 MOnb/n. ΠΟΟΠΘ ΗΟΟΤΜ>ΚΘΗΜΠ Η3ΗΗ0Γ0 3Η3ΗΘΗΜΠ ρΗ ΟΟΜΟΤΜΗΘΟΚΟΘ Η3ΒΠΘΗΜΘ pacTBopa οτηηοβμτοπ paBHbiM 0,1489.
PacTBop rManypOHaia UMHKa nonyHaioT M3 οοο6θηηο ημοτογο rManypoHaTa HaTpMB. OnMCaHHOrO B npMMepe 3. ΒΜβΟΤβ C flBa>KHbl flMCTMnnMpOBaHHOM BOflOM B CTepMnbHblX yCnOBMBX. 3aTeM paCTBOp OTCpMnbTpOBblBaiOT ΗΘΡΘ3 MeMāpaHHbIM $MnbTp (0,45 μ - pa3Mep nopbi). nonyHeHHbiM pacTBop μο>κθτ 6biTb TaKx<e Mcnonb30BaH b KanecTBe BemecTBa ΗΠΠ ΜΗΤϊΘΚΜΜΜ. ΠρΜΜθρ 9 14 ΠοπγΗΘΗΜΘ βοαηογο pacTBopa, copep>Kamero 0,2 βθο./ο6. % rnanypoHaTa UMHKa. Μ ΠΟΠγΗΘΗΜΘ Μ30Τ0ΗΜΗΘ0Κ0Γ0 paCTBOpa C ΠρΜΜΘΗΘΗΜΘΜ XnopMfla UMHK3. βΠΠ ΠΟΠγΗΘΗΜΠ ΚΟΗΘΗΗΟΓΟ 06teMa 100 ΜΠ Β3ΒΘΐυΜΒ310Τ 0,20 Γ rnanypoHaia HaTpMfl m pacTBopaioT b pacTBope xnopnna UMHKa κοημθητρθμμθμ 0,120 Monb/n.
PacTBopeHne μ ποπυηθημθ pacTBopa xnopMpa UMHKa 0,120 Monb/n προΒορπτ CnOCOāOM, npMBBfleHHblM B ΠρΜΜβρβ 1 (πγΤΘΜ Μ3ΜΘΗΘΗΜΠ ΚΟΠΜΗΘΟΤΒβ ΧΠΟρΜΟβ UMHKa).
OcMOTunecKoe paBneHne pacTBopa 0,154 Monb/n, hto 3κβμβ3πθητηο KOHueHTpaunu xnopnpa HaTpua, pH paBHO ot 5,3 no 5,4.
Coaep>KaHMe προτβΜΗβ: 0,015 μγ/μπ
HiicTOTa pacTBopa (Ha ochob3hmm μ3μθρθημπ cneKTpanbHOM nomoiuaTenbHOM CnOCOČHOCTM npM 1 60 HM C ΠρΜΜΘΗΘΗΜΘΜ 1-CM KKDBBTbl) A1 CM660: °-015 Οοπθρχοημθ HA: 1,96 μγ/μπ Bfl3KOCTb [η] c -> 0%: 15,9 on/r
PacTBOp nonyHaiOT c noMombio manypoHaTa Haipnn, onvicaHHoro b npMMepe 2, m npe>Kae Bcero Mcnonb3yioT ρππ πρμγοτοβπθημβ BemecTB, πρμμθηπθμβιχ b flepMaTonornn n κοομθτοπογμμ. Πρμμθρ 10 ΠοπγΗΘΗΜΘ βοαηογο pacTBopa, copepacamero 0,50 βθο./ο6. % rManypoHaia
HaTpMB, Μ ΠοπγΗΘΗΜΘ Μ30ΤΟΗΜΗΘ0Κ0Γ0 paCTBOpa C ΠρΜΜΘΗΘΗΜΘΜ miOK03bl.
PacTBop conep>KMT rManypoHaT ηβτρμα m pacneTHoe θκβμβθπθητηοθ ΚΟΠΜΗΘΟΤΒΟ XHOpMfla UMHK3. 12.50 μπ pacTBopa xnopMpa ΗβτρΜΠ κοημθητρβρμθμ 0,100 Monb/n flo6aBnniOT κ 0,50 r TManypoHaTa HaipMn, β3βθιιιθηηογο b 100-μπ μθρηομ κοπ6θ (χπορΜρ μμηκθ npyroM KOHpeHTpauMM μο>κθτ 6biTb Taoce Mcnonb30BaH, ho θγο κοπμηθοτβο ροπ>κηο ocTaBaTbca πρθχημμ). rManypoHaT Haipna Bbipep>KMBatOT b τθηθημθ 12 nacoB πππ Ha6yxaHMB b pacTBope xnopMpa UMHKa, ροβθπθηηογο qo 50 μπ CBOČOflHOM BOflOM, 3aTeM pacTBopBiOT npM βοτρπχμββημμ. 3aTeM počaBnniOT 24,50 μπ pacTBopa rniOK03bi KOHueHTpauMeīi 1,00 Monb/n μ ροεορπτ po οτμθτκμ cbočophom bopom.
OcMOTMHecKoe ρθβπθημθ pacTBopa 0,1495 Monb/n θκβμββπθητηο KOHueHTpauMM xnopMpa HaTpMB, 3ηθηθημθ pH paBHO 5,4. Oāiuan KOHueHTpauMB UMHKa 1,25x10-2 MOnb/n.
PacTBop nonyHaiOT c noMombra rManypoHaia HaipMa, onMcaHHoro b npMMepe 2, m npex<ae Bcero Mcnonb3yiOT ρππ πρμγοτοβπθημπ βθιρθοτβ. πρμμθηπθμμχ b pepMaTonorMM μ κοομθτοπογμμ. 15 LV 10965 Πρμμθρ 11 rionyHeHMe βορηογο pacTBopa, copepacaiuero 0,2 bbc. % rnanypOHaia UMHKa, m nonyMeHne μ30τοημμθοκογο pacTBopa c πρμμθηθημθμ rriK)K03bi.
PacTBop coflep>Km rnanypoHaT ηθτρμπ m pacneTHoe θκβμβθπθητηοθ κοπμηθοτβο xnopnfla UMHKa. 5,0 μπ pacTBopa xnopnpa UMHKa κοηρθητρθρμθμ 0,100 Monb/π flo6aBriflfOT κ 0,20 r rnanypoHaTa naipm, B3BeiueHHoro β 100-μπ μθρηομ κοπδθ, 3aTeM očteM ροΒορπτρο 50 μπ c noMOinbio ρθμοημ3μροβθηηομ BOflbi. Ilocne Ha6yxaHMfl b τθηθημθ hohm rnanypoHaT HaTpua pacTBopaiOT npM BCTpaxMBaHMM, po6aBnaioT 27,0 μπ pacTBopa rn»OK03bi KOHpeHTpauMeM 1,00 Monb/n n Kon6y HanonHflKDT no οτμθτκμ CBOČOPHOM BOflOM.
OcMOTunecKoe ρθβπθημθ pacTBopa 0,151 Monb/n θκβμβθπθητηο KOHueHTpauMM xnopnjqa HaTpua, pH paBHO ot 5,6 po 5,7. 06man KOHueHTpauMn unHKa 5x10“3 Monb/n. Πρμμθρ 12 nonyMeHMe βοαηογο pacTBopa, copep>Kamero 0,50 Bec./o6. % rManypoHaTa UMHKa. m nonyHeHMe μ30τοημηθοκογο pacTBopa c πρμμθηθημθμ copČMTona.
PacTBop rManypoHaTa UMHKa nonynaK)T b CTepMnbHbix ycnoBMnx M3 rManypoHaTa HaTpMJļ BbICOKOM HMCTOTbl, ΟΠΜΟβΗΗΟΓΟ Β ΠρΜΜθρβ 3, Μ ΑΜ0ΤΜΠΠΜρ0Β3ΗΗ0Μ BOflbl. PacTBop copep>KMT 3κβμβ3πθητηβιθ KonMHecTBa xnopMpa UMHKa. paccHMTaHHbie Ha rManypoHaT HaTpMH. npouecc ποΓψΜΘΗΜΗ προΒοηπτ cnocoāoM, yKa3aHHbiM b npMMepe 10, 3a ΜΟΚΠΙΟΗΘΗΜΘΜ ΤΟΓΟ, ΗΤΟ ΒΜΘΟΤΟ paCTBOpa m»OK03bl 23,50 ΜΠ pacTBopa COpČMTOna KOHueHTpauMeM 1,00 Monb/n (182,19 r D-cop6MTona b 1 n) ροδβΒππιοτ b pacTBOp rManypoHaTa UMHKa. nonyHeHHblM pacTBOp OTCfjMnbTpOBbIBaKDT ΗΘΡΘ3 MGMČpaHHblM CļjMnbTp (0,45 μ -pa3Mep nopbi). 3tot pacTBOp μο>κθτ 6biTb Mcnonb30BaH pnn mo6bix uenePi. κροΜθ ΜΗΒΘΚΜΜΜ.
OcMOTMMecKoe paBneHMe pacTBopa 0,1520 Monb/n SKBMBaneHTHO KOHueHTpauMM xnopMpa HaTpMH, 3ηθηθημθ pH paBHO 5,5, o6maa KOHueHTpauMn UMHKa 1.25x10~2 Monb/n. ΠρΜΜΘΡ 13 nonyHeHMe βορηογο pacTBopa. copep>Kamero 0,2 Bec./οδ. % rManypoHaTa UMHKa, m nonyweHMe μ3οτοημηθοκογο pacTBopa c πρμμθηθημθμ copČMTona.
PacTBop cooep>KMT θκβμβθπθητηοθ κοπμηθοτβο xnopMpa UMHKa, paccHMTaHHoe Ha rManypoHat HaTpMfl. 16
PacTBOp rnanypoHaTa um-iKa nonyHa»OT b CTepnnbHbix ycnoBnnx M3 rnanypoHaTa HaTpn« BbicoKoii ημοτοτμ, xax yxa3aHO b npuMepe 3, βμθοτθ c flBax<pbi aMCTMnnupOBaHHOM BOflOil. npouecc nonyHeHMfl προΒορπτ cnoco6oM, onncaHHOM b npuMepe 12, 3a ΜΟκπιοΗβΗΜβΜ τογο, Ητο 0,2 r rnanypoHaTa HaTpua pacTBOpniOT β5μπ pacrreopa xnopnpa UHHKa KOHueHTpaLineii 0,100 Monb/n, 3aieM poāaBnnioT 26,50 μπ pacTBOpa copčMTona KOHuei-npauMeii 1 Monb/n μ ποβοππτ pacTBOop no 100 μπ. flonyHeHHbiii pacTBop OTCpMnbTpoBbiBaioT nepe3 MeMČpaHHbiii φΐ/inbTp (0,45 μ -pa3Mep nopbi). 3tot pacTBop Μθ>κβτ 6biTb ncnonb3oeaH pnn nto6bix ueneii, κροΜβ MHbeKUMM.
OcMOTunecKoe paBneHne pacTBopa 0,1501 Monb/n 3κβμβ3πθητηο KOHueHTpauMM xnopnna Haipna, 3HaMeHne pH paBHO 5,6, očman KOHLieHTpaunn unHKa 5x10-3 Monb/n.
Conep>KaHMe npoīenHa: 0,016 μγ/μπ
HncTOTa pacTBopa (Ha ocHOBaHun n3MepeHna cneKTpanbHOM nornomaienbHOM CnOCOāHOCTM npn 160 HM C ΓφΜΜβΗβΗΜβΜ 1-CM KKDBeTbl) A1 CM660: ū>ū1°
Conep>KaHMe rnanypoHaTa: 2,03 μγ/μπ
Bn3K0CTb [η] c -» 0%: 16,1 pn/r flpHMepbi 14-26 B cnepyiouuix npnMepax KOMnoHeHTbi pa3nnHHbix BemecTB (pnn $apMaKonornn H ΚΟΟΜβΤΟΠΟΓΜΜ) ΠρΜΒβρβΗΜ B ΟΟΟΤΒβΤΟΤΒΜΜ C peiļenTypoii, BblāpaHHOii HaMM. nonyHeHne μ30τοημμθοκμχ pacTBOpoe rnanypoHaTa unHKa onncaHO b npnBepeHHbix Bbirne npnMepax. 3pecb τθρμμη ”ρμοτμππμροβ3ηηη3π Bopa ρππ MH-beKunti” cooTBeTCTByeT pBax<pbi nncTnnnnpoBaHHoii eope, nonyHeHHoii b CTepunbHbix ycnoBnnx. I. HHbeKLļMOHHbie pacTBopbi.
BemecTBa, npuBepeHHbie b npnMepax 14-17, ncnonb3yiOT pnn BHyTpMKO>KHbix MHbeKLiMM, a b npuMepe 18 - pnn BHyTpnrna3Hbix unteKunii. Ακτμβημμ κομποηθητ, onncaHMe κοτορογο npneeneHO b npuMepe 3, ncnonb3yiOT b paHHbix npnMepax. Πρμμθρ 14 AKTHBHbiii κομποηθητ rnanypoHaTa unHKa 2,0 μγ CopāHTon 48,3 ΜΓ 17 LV 10965
KoHeHHbm očteM βοαηογο pacTBopa, nonyHeHHbin c noMombio flUCTUnnMpOBaHHOii BOflbl, flHfl MHbeKUMM 1,0 ΜΠ. Πρμμθρ 15 Ακτμβηημ κομποηθητ rnanypoHaTa UMHKa 5,0 μγ Οορδητοπ 42,8 μγ Κοηθηημμ očteM βοαηογο pacTBopa, nonyHeHHbin c noMoiflbio flklCTUnnupOBaHHOii BOflbl, flHH MHteKUMM 1,0 ΜΠ. Πρμμθρ 16 Ακτμβηνμ κομποηθητ rManypoHaia μμηκθ 2,0 μγ nponMn-napa-rMppoKCM6eH3oaT 0,05 μγ MeTMn-napa-rMnpoKCM6eH3oaT 0,5 μγ rniOK03a 48,6 μγ Κοηθηηημ ο6ι.θμ βοαηογο pacTBopa. nonyweHHoro c noMOiubto ΡΜΟΤΜΠΠΜρΟΒΒΗΗΟΜ BOflbl, ΑΠΗ MHteKUMM 1,0 ΜΠ. ΠρΜΜΘΡ 17 AKTMBHbiii κομποηθητ rnanypOHaTa UMHKa 5,0 μγ nponMn-napa-rMflpoKCM6eH3oaT 0,05 μγ MeTMn-napa-rnflpoKCM6eH3oaT 0,5 μγ rmoK03a44,1 μγ Κοηθηημμ očteM βοαηογο pacTBopa. nonyneHHoro c noMombio flMCTMnnMpOBaHHOM BOflbl, flHfl MHbeKUMM 1,0 ΜΠ. Πρμμθρ 18 AKTMBHbIM ΚΟΜΠΟΗΘΗΤ manypOHaTa UMHKa 10,0 ΜΓ Cop6aT Kanna 1,0 μγ Οορδητοπ 41,0 μγ
KoHeHHbiii ο6τ>θμ βοαηογο pacTBopa. nonyHeHHoro c noMombio flMCTMnnMpOBaHHOM BOflbl, flHH MHbeKUMM 1,0 ΜΠ.
BeinecTBa, npMBefleHHbie b npMMepax 20-28, Mcnonb3yiOTca, b ochobhom. b AepMaTonornn μ κοομθτοπογμμ. Ακτμβηβιμ κομποηθητ, npMBeneHHbiM b npMMepe 2, Mcnonb3yioT b flaHHbix npMMepax. II. PacTBopbi flna μθοτηογο πρμμθηθημπ. 18 Πρημθρ 19 AKTMBHbiii κομποηθητ rnanypoHaTa unHKa 5,0 μγ CopčaT Kanna 1,0 μγ AueiaT HaTpna 24,6 μγ
KoHeHHbin ο6^θμ βοαηογο pacTBopa, nonyHeHHbin c noMombio ancTnnnnpOBaHHon BOflbj 1,0 μπ. flpnMep 20 AKTHBHbiii κομποηθητ rnanypOHaia unHKa 2,0 μγ CopčaT Kanna 1,0 μγ Copčmon 48,3 μγ Κοηθηημη oāteM βοαηογο pacTBopa. nonyHeHHbin c noMombio oncTnnnnpoBaHHon BOflbi 1,0 μπ. III. Tenn pna μθοτηογο npnMeHeHna ΠρηΜθΡ 21 AKTnBHbin κομποηθητ rnanypoHaTa unHKa 20,0 μγ nonnMepn3aT aKpnnoBon KncnoTbi 200 μγ ΓnnpoKcnu HaTpna 30% KOHueHTpaunn 50 μγ Cop6aT Kanna 10 μγ HncTnnnnpoBaHHaa Boua no 10,0 μγ. ΠρηΜΘρ 22 AKTnBHbin κομποηθητ rnanypoHaTa unHKa 20,0 μγ llonnMepn3aT aKpnnoBon KncnoTbi 50 μγ ΓnupoKcnu HaTpna 30% KOHueHTpaunn 40 μγ llponnneHrnnKonb 1500 μγ CopčaT Kanna 10 μγ flncTnnnnpOBaHHaa Boua no 10,0 μγ. IV. llacTbi n Ma3n flna μθοτηογο npnMeHeHna ΠρηΜΘΡ 23 Ακτηβημη κομποηθητ rnanypoHaTa unHKa 50 μγ 19 19 LV 10965
CopčaT Kanna 10 μγ MarKnn čenbīn bock 125 μγ Cop6nTaHoneaT150 μγ LļeTnnoBbin CTeapnHOBbin cnnpT 840 μγ rnnuepnHMOHOCTeapaT 1100 μγ nponnneHrnnKonb 4750 μγ flncTnnnnpoBaHHaa Bopa po 10 r. llpnMep 24 AKTnBHbin κομποηθητ rnanypoHaia KOčanbTa 50 μγ CopčaT Kanna 10 μγ Man-cnn 6enbin bock 125 μγ CopāmaHoneaT 150 μγ UemnoBbin CTeapnHOBbin cnnpT 840 μγ rnnuepnHMOHOCTeapaT 1100 μγ nponnneHrnnKonb 4750 μγ JļncTnnnnpoBaHHaa Bopaflo 10 r. ΠρηΜθΡ 25 AKTnBHbin κομποηθητ rnanypoHaTa unHKa 50 μγ 2-nļ)eHOKcnaTaHon 100 μγ nopnncynbCf)aT HaTpna 100 μγ
UeTnnnanbMHTaT 400 μγ CTeapnH 400 μγ CTeapnHOBbin cnnpT 450 μγ
UeTnnoBbin cnnpT 450 μγ
Benbīn Ba3ennH 500 μγ nponnneHrnnKonb 550 μγ
TnnuepnH 600 μγ flHCTnnnnpoBaHHaa Bopa no 10 r.
HpnMep 26 ΑκτΗΒΗΝίί κομποηθητ rnanypoHaTa KoāanbTa 50 μγ 2-$eHOKcneTaHon 100 μγ flopnncynb$aT HaTpna 100 μγ
UeTnnnanbMnTaT 400 μγ CTeapnH 400 μγ CTeapnHOBbin cnnpT 450 μγ 20
UeTMnoBbiii οπηρτ 450 μγ BenbīPi Ba3ennH 500 μγ nponnneHrnnKonb 550 μγ rnnuepnH 600 μγ JļucTMnnupOBaHHafl Boqa no 10 r. flpuMep 27 Ακτηβηηη κομποηθητ rnanypoHaTa qnHKa 50 μγ MnKpoKpncTannnHecKHM napacpHH 250 μγ nponnneHrnnKonb 500 μγ CopOmon 400 μγ >KMBOTHblii BOCK (aueTMnupOBaHHblM) 500 ΜΓ Benbīii Ba3ennH ,qo 10 r. V. BemecTBa ηπη fle3HH<ļ>eKunn h py6qeBaHna γηοηηνχ paH h ο>κογοβ Πρμμθρ 28 AKTMBHbiii κομποηθητ rnanypoHaTa UHHKa 10 μγ Cop6aT Kanna 1,0 μγ rnppo0nnbHbiii KonnonpHbiii pnoKcnn κρΘΜΗΐ/ia 50 μγ CopānTon flo 1 r. 21 LV 10965
Φ Ο P Μ Υ Π A M30BPETEHM5R 1. CnOCOČ ΠΟΓψΜΘΗΜΗ Κ0ΜΠ03ΙΊ14ΜΜ ΠγΤΘΜ CMeUJMBaHMfl βΚΤΜΒΗΟΓΟ Κ0ΜΠ0ΗΘΗΤ3 c o6biMHbiMu ooēaBKaMU n/nnn ηοομτθπαμμ, OTnunaioiuMMca τθμ, mto b KanecTBe aKTUBHoro κομποηθητ3 Acnorib3yioT accounaT flenpoTOHMpOBaHHoii rna/iypoHOBoti KMcnoTbi c MOHaMM 3d Metanna ηθτβθρτογο nepnopa nepnonunecKoii taānuubi. 22 LV 10965
ΡΕΦ EPAT ΙΊ3θ6ρθΤΘΗΜΘ OTHOCMTCJ1 K Cn0C06y ΠΟΠγΗΘΗΜη K0Mn03MUMM, coflepacamvu HOBbie accoLinaTbi (KOMnneKCbi) AenpoTOHnpoBai-ΐΗθίί rnanypoHOBoii KucnoTbi c MOHaMM 3d Meianna ηθτβθρτογο nepnona nepnoflMHecKoii Tačnmļbi u b KawecTBe aKTMBHblX ΚΟΜΠΟΗΘΗΤΟΒ ΜΠΜ ΗΟΟΜΤΘΠΘΜ. ripeflno>KeHHbie κομπο3μμμμ ncnonb3yiOT b «anecTBe cf)apMai4eeTWHecKMx wm κοομθτμηθοκμχ cpeflCTB, ohm πο3βοπακ)τ ycKopmb npouecc 3nnTenn3auMn ynacTKOB Tena, 3a>KMBneHne 6eqpeHHbix α3β, nponeaoHeii m t. a.
Claims (1)
- LV 10965 IZGUDROJUMA FORMULA 1. Kompozīcijas iegūšanas paņēmiens, aktīvā komponenta sajaukšanas ceļā ar parastām piedevām un/vai nesējiem, a t š ķ i r a s ar to, ka par aktīvo komponentu izmanto deprotonētās hialuronskābes asociētu ar periodiskās sistēmas ceturtā perioda 3d metāla joniem.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU89891A HU203372B (en) | 1989-02-24 | 1989-02-24 | Process for producing hyaluronic associates and pharmaceutical compositions and cosmetics comprising such active ingredient |
| PCT/HU1990/000013 WO1990010020A1 (en) | 1989-02-24 | 1990-02-20 | Novel compositions containing hyaluronic acid associates and a process for preparing same |
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| Publication Number | Publication Date |
|---|---|
| LV10965A LV10965A (lv) | 1995-12-20 |
| LV10965B true LV10965B (en) | 1996-08-20 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LVP-92-687A LV10112B (en) | 1989-02-24 | 1992-12-30 | Associations of deprotonated hyaluronic acid, compositions containing it, method for preparing thereof, process for preparing water solution of hyaluronic acid zinc salt |
| LVP-93-747A LV10965B (en) | 1989-02-24 | 1993-06-29 | Process for producing of compositions conteining hyaluronic acid associate |
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| Application Number | Title | Priority Date | Filing Date |
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| LVP-92-687A LV10112B (en) | 1989-02-24 | 1992-12-30 | Associations of deprotonated hyaluronic acid, compositions containing it, method for preparing thereof, process for preparing water solution of hyaluronic acid zinc salt |
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| JP5763953B2 (ja) * | 2011-03-31 | 2015-08-12 | ロート製薬株式会社 | 外用組成物 |
| CN102961396A (zh) * | 2012-12-17 | 2013-03-13 | 程玉李 | 透明质酸金属盐在制备治疗皮肤病药物中的应用、其药物组合物及其制备方法 |
| CA3100536A1 (en) | 2013-11-03 | 2015-05-07 | The Regents Of The University Of California | Ionic liquids for transdermal drug delivery |
| KR102552848B1 (ko) * | 2016-08-29 | 2023-07-06 | 더 리전츠 오브 더 유니버시티 오브 캘리포니아 | 피부 치료를 위한 이온성 약제에 기초한 국소 제형 |
| KR20190070327A (ko) | 2016-09-21 | 2019-06-20 | 네슬레 스킨 헬스 소시에떼 아노님 | 2가 아연 양이온을 갖는 히알루론산 겔 |
| WO2019001784A1 (en) | 2017-06-28 | 2019-01-03 | Nestlé Skin Health Sa | HYALURONIC ACID GEL WITH A DIVALENT CATION |
| AR112480A1 (es) | 2017-08-24 | 2019-10-30 | Novo Nordisk As | Composiciones de glp-1 y sus usos |
| AU2021208601A1 (en) | 2020-02-18 | 2022-07-28 | Novo Nordisk A/S | Glp-1 compositions and uses thereof |
| CN111647100B (zh) * | 2020-07-14 | 2022-03-01 | 山东华熙海御生物医药有限公司 | 一种高分子量透明质酸锌的制备方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US441973A (en) | 1890-12-02 | rapieff | ||
| US3074927A (en) * | 1960-04-12 | 1963-01-22 | Paul D Saltman | Metallic complexes of reducing sugars |
| US4141973A (en) * | 1975-10-17 | 1979-02-27 | Biotrics, Inc. | Ultrapure hyaluronic acid and the use thereof |
| HU172831B (hu) * | 1976-03-31 | 1978-12-28 | Egyt Gyogyszervegyeszeti Gyar | Sposob poluchenija kompleksov oligo- i poligalakturonnyk kislot s ionami zhiznenno vazhnykh metallov |
| US4303676A (en) | 1980-03-21 | 1981-12-01 | Balazs Endre A | Hyaluronate based compositions and cosmetic formulations containing same |
| IT1229075B (it) | 1985-04-05 | 1991-07-17 | Fidia Farmaceutici | Medicamenti per uso topico, ottenuti tramite l'impiego dell'acido ialuronico |
| US4623539A (en) | 1983-02-04 | 1986-11-18 | Tunc Deger C | Nutrient barrier polysaccharide compositions and method of use |
| NO161573C (no) | 1983-11-25 | 1989-08-30 | Miles Inc | Fremgangsmaate til fremstilling av hyaluronsyre. |
| JPS61286310A (ja) * | 1985-06-10 | 1986-12-16 | Kanebo Ltd | メ−クアツプ化粧料 |
| WO1987005517A1 (en) * | 1986-03-14 | 1987-09-24 | Bio-Technology General Corp. | Heavy metal salts of hyaluronic acid useful as antimicrobial agents |
| US4746504A (en) * | 1986-03-14 | 1988-05-24 | Bio-Technology General Corp. | Heavy metal salts of hyaluronic acid and their use as antimicrobial agents |
| US4742215A (en) * | 1986-05-07 | 1988-05-03 | Personal Computer Card Corporation | IC card system |
| US5145841A (en) * | 1987-03-19 | 1992-09-08 | Arthropharm Pty. Limited | Anti-inflammatory compounds and compositions |
-
1989
- 1989-02-24 HU HU89891A patent/HU203372B/hu unknown
-
1990
- 1990-02-20 UA UA94061636A patent/UA39174C2/uk unknown
- 1990-02-20 KR KR1019900702327A patent/KR960015624B1/ko not_active IP Right Cessation
- 1990-02-20 CA CA002027596A patent/CA2027596C/en not_active Expired - Lifetime
- 1990-02-20 UA UA4895005A patent/UA26324A/uk unknown
- 1990-02-20 WO PCT/HU1990/000013 patent/WO1990010020A1/en active IP Right Grant
- 1990-02-20 ES ES90903397T patent/ES2061016T3/es not_active Expired - Lifetime
- 1990-02-20 RU SU904831382A patent/RU2099350C1/ru active
- 1990-02-20 AT AT90903397T patent/ATE98964T1/de not_active IP Right Cessation
- 1990-02-20 AU AU51088/90A patent/AU623232B2/en not_active Expired
- 1990-02-20 DK DK90903397.9T patent/DK0413016T3/da not_active Application Discontinuation
- 1990-02-20 JP JP2503644A patent/JP2571312B2/ja not_active Expired - Lifetime
- 1990-02-20 DE DE69005394T patent/DE69005394T2/de not_active Expired - Lifetime
- 1990-02-20 EP EP90903397A patent/EP0413016B1/en not_active Expired - Lifetime
- 1990-02-22 CZ CS90857A patent/CZ281000B6/cs not_active IP Right Cessation
- 1990-02-22 DD DD90338061A patent/DD292263A5/de not_active IP Right Cessation
- 1990-02-22 MY MYPI90000280A patent/MY105168A/en unknown
- 1990-02-22 PT PT93237A patent/PT93237B/pt active IP Right Grant
- 1990-02-22 IE IE63790A patent/IE62408B1/en not_active IP Right Cessation
- 1990-02-22 IL IL9348990A patent/IL93489A/en not_active IP Right Cessation
- 1990-02-22 ZA ZA901357A patent/ZA901357B/xx unknown
- 1990-02-22 GR GR900100137A patent/GR1000869B/el not_active IP Right Cessation
- 1990-02-22 SK SK857-90A patent/SK85790A3/sk not_active IP Right Cessation
- 1990-02-23 AR AR90316230A patent/AR243538A1/es active
- 1990-02-23 CN CN90100904A patent/CN1024557C/zh not_active Expired - Lifetime
- 1990-02-23 PL PL90283942A patent/PL163417B1/pl unknown
- 1990-02-23 CN CN93109689A patent/CN1051228C/zh not_active Expired - Lifetime
- 1990-10-17 FI FI905109A patent/FI101707B/fi active IP Right Grant
- 1990-10-23 NO NO904584A patent/NO301169B1/no not_active IP Right Cessation
-
1991
- 1991-04-11 RU SU914895005A patent/RU2021304C1/ru active
-
1992
- 1992-08-10 US US07/928,154 patent/US5554598A/en not_active Expired - Lifetime
- 1992-12-30 LV LVP-92-687A patent/LV10112B/lv unknown
-
1993
- 1993-06-17 GE GEAP1993894A patent/GEP19981358B/en unknown
- 1993-06-29 LV LVP-93-747A patent/LV10965B/lv unknown
- 1993-08-12 GE GEAP19931400A patent/GEP19971015B/en unknown
- 1993-10-26 LT LTIP1418A patent/LT3806B/lt not_active IP Right Cessation
- 1993-11-18 LT LTIP1474A patent/LT3873B/lt not_active IP Right Cessation
-
1994
- 1994-03-01 BG BG098631A patent/BG61515B2/bg unknown
-
1995
- 1995-06-07 HU HU95P/P00167P patent/HU211465A9/hu unknown
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1998
- 1998-03-12 HK HK98102052A patent/HK1003003A1/xx not_active IP Right Cessation
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