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Mannose thiab Mannitol

2025-03-21 2025

  1. Freeze-drying, hu ua freeze-drying, yog ib txoj kev ziab uas ua ntej-freezes cov tshuaj tov uas yuav tsum tau qhuav rau hauv cov khoom thiab ces ncaj qha sublimates cov dej los ntawm lub xeev khov yam tsis mus dhau lub xeev cov kua nyob rau hauv qis kub thiab tsis tshua muaj siab tej yam kev mob. Vim tias tag nrho cov txheej txheem kev ua haujlwm yog nyob rau hauv qhov kub thiab txias, txoj kev no yog tshwj xeeb tshaj yog haum rau kev npaj cov tshuaj tiv thaiv tshav kub-sensitive protein. Cov tshuaj khov-qhuav cov protein tau xoob zoo li ncuav mog qab zib, uas tsis yog tsuas yog ua rau kev khaws cia tab sis kuj tseem muaj txiaj ntsig rau kev rov ua dua ntawm cov tshuaj protein tom qab rov ua dua. Obviously, khov-drying thev naus laus zis muab txoj hauv kev zoo rau kev npaj tshuaj protein nrog cov khoom tsis ruaj khov ntawm lub cev thiab tshuaj lom neeg. Txawm li cas los xij, cov txheej txheem khov-ua kom qhuav yog txheej txheem hloov pauv theem, thiab muaj ntau yam ua rau cov protein denaturation nyob rau hauv cov txheej txheem ntawm khov, khov-thawing, ziab thiab cia, yog li qee cov tshuaj tiv thaiv feem ntau siv los tswj cov protein nyob hauv daim ntawv tshuaj. Qab Zib, feem ntau siv excipient hauv cov khoom khov-qhuav, pawg hydroxyl hauv nws cov qauv tuaj yeem hloov cov hydrogen daim ntawv cog lus ntawm cov protein thiab dej kom muaj cov nyhuv ruaj khov, yog cov tsis muaj kev ruaj ntseg ntawm cov protein, thiab tuaj yeem ua lub luag haujlwm tiv thaiv hauv ntau theem ntawm khov-qhuav (xws li khov, khov-thaw thiab sublimation). Cov nyhuv tiv thaiv ntawm cov piam thaj muaj feem xyuam rau hom protein thiab disaccharides, thiab disaccharides yog cov kev tshawb fawb tshaj plaws thiab lees paub cov tshuaj tiv thaiv zoo tshaj plaws. Sucrose yog ib qho disaccharide uas tsim los ntawm ib qho molecule ntawm qabzib thiab ib lub molecule ntawm fructose, uas yog tshuaj lom neeg ruaj khov thiab feem ntau muaj cov qauv amorphous, thiab ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv cov qauv kev hloov pauv ntawm cov protein, thiab txuas ntxiv thiab sib sau ua ke ntawm cov proteins thaum lyophilization thiab cia. Piv nrog rau sucrose, trehalose muaj qhov hloov pauv ntawm iav ntau dua, txo cov dej noo induction, thiab txo qis dua. Cov txiaj ntsig zoo no qhia tias trehalose tuaj yeem muaj qhov kev thov dav dua. Cawv, xws li mannitol, feem ntau yog siv los ua cov fillers uas crystallize ntawm qeeb khov los muab cov qauv kev txhawb nqa rau cov khoom nquag thiab tsis ua rau nws.
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    Mannose yog monosaccharide, soluble hauv dej, me ntsis soluble hauv ethanol. Tsis muaj xim lossis dawb crystalline hmoov. Nws ua lub luag haujlwm tseem ceeb hauv tib neeg cov metabolism, tshwj xeeb tshaj yog nyob rau hauv cov txheej txheem glycosylation ntawm cov proteins tshwj xeeb. Nws yog ib qho nyuaj rau mannose absorbed los ntawm tib neeg lub cev, thiab nws yuav raug tshem tawm los ntawm tib neeg lub cev sai sai tom qab noj, feem ntau yog los ntawm lub raum metabolism, thiab tag nrho cov metabolic voj voog yog txog yim teev. Kev noj cov mannose tsis ua rau cov ntshav qab zib nce ntxiv, yog li nws yog hom suab thaj uas qee cov neeg mob ntshav qab zib noj tau. Nyob rau hauv qhov xwm txheej, mannose muaj nyob hauv lub xeev dawb hauv qee cov txiv hmab txiv ntoo, xws li cranberries, txiv apples, txiv kab ntxwv, thiab lwm yam. Hauv tib neeg lub cev, mannose tau faib rau txhua cov ntaub so ntswg thiab ntshav, suav nrog daim tawv nqaij, kab mob thiab cov hlab ntsha. Hauv cov ntaub so ntswg, mannose koom nrog hauv kev sib txuas ntawm glycoproteins uas tswj kev ua haujlwm ntawm autoimmune system. Cov kev tshawb fawb soj ntsuam yav dhau los tau pom tias mannose tuaj yeem kho thiab tiv thaiv kab mob urinary, yog li qee cov khoom noj qab haus huv txawv teb chaws nrog mannose yog cov khoom tseem ceeb yog siv los tswj cov kab mob urinary. Mannitol yog qab zib cawv, feem ntau txo los ntawm qab zib (mannose), yog ib qho isomers ntawm sorbitol, soluble hauv dej, dawb crystalline hmoov, muaj qab zib saj zoo li sucrose. Mannitol tuaj yeem siv tsis tau tsuas yog ua tus neeg saib xyuas pob txha zoo xwb, tab sis kuj yog tus tiv thaiv lyophilized protein hauv qee cov tshuaj. Kev tiv thaiv ntawm mannitol ntawm cov protein muaj feem xyuam rau nws cov concentration thiab morphological qauv, thiab nws cov concentration yog qee zaum cuam tshuam nrog crystal morphology. Nws feem ntau ntseeg tias amorphous mannitol muaj cov haujlwm ntawm stabilizing protein thaum crystallized mannitol poob nws txoj haujlwm tiv thaiv. Mannitol concentrations ntawm 1% los yog tsawg dua tiv thaiv kev sib sau ntawm cov tshuaj protein los ntawm kev tsim cov qauv amorphous, tab sis cov ntsiab lus siab ntawm mannitol zoo li crystallize thiab txhawb kev sib sau ntawm cov tshuaj protein. Rau feem ntau cov proteins, kev khaws cia ntawm 4 ° C tsuas yog luv luv (kwv yees li 1 lub lis piam) tom qab rov raug ncua. Rau kev khaws cia ntev, nws raug nquahu kom npaj cov diluents (uas yuav tsum muaj cov carrier proteins, xws li 0.1% BSA, 5% HSA, lossis 10% FBS) thiab tom qab ntawd subpack khov ntawm -20 ℃ lossis -80 ℃. Nws yog ib qho tseem ceeb kom tsis txhob rov khov thiab thawing, vim txhua qhov khov thiab thawing yuav ua rau ib feem ntawm cov protein tsis ua haujlwm. Trehalose thiab mannitol feem ntau yog ntxiv nrog 8% (ntau los ntawm ntim) raws li cov tshuaj tiv thaiv lyophilized. Trehalose tuaj yeem tiv thaiv qhov kev hloov pauv theem nrab ntawm cov protein thiab ncab thiab sib sau ua ke ntawm cov protein thaum lyophilization. Mannitol kuj yog siv dav siv lyophilized tiv thaiv thiab muab tub lim uas tuaj yeem txo qhov sib xyaw ntawm qee cov proteins tom qab lyophilization. Cov muab tub lim tuaj yeem muab cov qauv tsim nyog rau lub ncuav mog qab zib khov-qhuav, ua kom zoo zoo ntawm lub ncuav mog qab zib khov-qhuav, thiab tsim cov qauv pore. Porosity yog qhov yuav tsum tau ua ua ntej rau sublimation ntawm cov dej khov, thiab cov pores loj tuaj yeem sublimate sai dua, yog li thawj lub sij hawm ziab tuaj yeem txo. Qhov sib ntxiv ntawm cov fillers ua rau lub sij hawm luv luv (cov khoom kub Tp?Tg' lossis Tc) thiab tuaj yeem siv los ua ib txoj hauv kev los txhim kho cov txheej txheem biopharmaceutical lyophilization. Feem ntau qhov piv ntawm stabilizer rau muab tub lim yuav tsum yog tsawg kawg yog 1: 2 los muab qhov tsim nyog crystallization ntawm muab tub lim. Qhov tshwm sim lattice muab kev txhawb nqa txhua yam rau cov khoom hauv lawv lub xeev amorphous. Saum toj no Tg', lub xeev amorphous tsim los ntawm kev npaj cov txheej txheem tsis nruj txaus los txhawb nws tus kheej qhov hnyav thiab yuav vau mus rau hauv cov siv lead ua network. Ua tsaug rau kev txhawb nqa txhua yam, kev sib tsoo tuaj yeem tiv thaiv txawm tias ziab kub siab dua Tg' (lossis txawm tias Tc). Nyob rau hauv formulations nrog protein ntau ntau