0102030405
Mannose & Mannitol
2025-03-21
- Kuwumitsa-kuzizira, komwe kumatchedwa kuunika kozizira, ndi njira yowumitsa yomwe imayimitsa njira yothetsera mankhwala yomwe imayenera kuumitsidwa kukhala yolimba ndiyeno imatsitsa madzi kuchokera kumalo oundana popanda kudutsa mumadzi ozizira pansi pa kutentha kochepa komanso kupanikizika kochepa. Chifukwa ntchito yonseyi imakhala yotsika kutentha, njirayi ndi yabwino kwambiri pokonzekera kukonzekera kwa mankhwala opangira mapuloteni. Mapuloteni owumitsidwa owumitsidwa anali otayirira ngati keke, zomwe sizinangothandiza kuti zisungidwe komanso zimathandizira kubwezeretsanso kwa mankhwala a protein pambuyo pakuwonongekanso. Mwachiwonekere, ukadaulo wowumitsa kuzizira umapereka njira yabwino yokonzekera zopangira zopangira mapuloteni okhala ndi zinthu zosakhazikika zakuthupi ndi zamankhwala. Komabe, kuzizira kowuma ndi njira yovuta yosinthira, ndipo pali zinthu zambiri zomwe zimapangitsa kuti mapuloteni awonongeke panthawi ya kuzizira, kuzizira, kuyanika ndi kusungirako, kotero ena otetezera nthawi zambiri amagwiritsidwa ntchito kuti akhazikitse mapuloteni mu mankhwala. Shuga, ndi ambiri ntchito excipient mu amaundana-zouma zouma, gulu hydroxyl mu dongosolo lake akhoza m'malo hydrogen chomangira pakati mapuloteni ndi madzi kupereka khola zotsatira, ndi sanali enieni stabilizer wa mapuloteni, ndipo akhoza kuchita mbali zina zoteteza mu magawo osiyanasiyana amaundana-kuyanika (monga kuzizira, amaundana-thaw ndi subli). Chitetezo cha shuga chimagwirizana ndi mtundu wa mapuloteni ndi ma disaccharides, ndipo ma disaccharides ndi omwe amaphunziridwa kwambiri komanso odziwika kuti ndi othandiza kwambiri. Sucrose ndi disaccharide wopangidwa ndi molekyu imodzi ya shuga ndi molekyulu imodzi ya fructose, yomwe imakhala yosasunthika pamankhwala ndipo nthawi zambiri imakhala ndi mawonekedwe aamorphous, ndipo imagwira ntchito yofunika kwambiri poletsa kusintha kwa mapuloteni achiwiri, komanso kukulitsa ndi kuphatikizika kwa mapuloteni pa lyophilization ndi kusunga. Poyerekeza ndi sucrose, trehalose imakhala ndi kutentha kwapamwamba kwa galasi, kutsika kwa chinyezi, komanso kuchepetsa kuchepa. Ubwinowu ukuwonetsa kuti trehalose ikhoza kukhala ndi chiyembekezo chochulukirapo. Mowa, monga mannitol, nthawi zambiri amagwiritsidwa ntchito ngati zodzaza zomwe zimanyezimira pang'onopang'ono kuzizira kuti zithandizire chigawo chogwira ntchito ndipo samachita nazo.
Mannose ndi monosaccharide, sungunuka m'madzi, sungunuka pang'ono mu Mowa. Ufa wopanda mtundu kapena woyera wa crystalline. Zimagwira ntchito yofunika kwambiri mu metabolism yaumunthu, makamaka mu ndondomeko ya glycosylation ya mapuloteni enieni. Ndizovuta kuti mannose atengeke ndi thupi la munthu, ndipo amatulutsidwa ndi thupi la munthu atangomwa, makamaka kudzera mu metabolism ya impso, ndipo kagayidwe kake kake kamakhala pafupifupi maola asanu ndi atatu. Kudya mannose sikumayambitsa kukwera kwa shuga m'magazi, choncho ndi mtundu wa shuga umene anthu ena odwala matenda a shuga angadye. Mwachilengedwe, mannose amakhalapo mwaulere mu zipatso zina, monga cranberries, maapulo, malalanje, ndi zina zotero. Mu thupi la munthu, mannose amagawidwa m'magulu onse ndi magazi, kuphatikizapo khungu, ziwalo ndi mitsempha. Mu minyewa iyi, mannose imakhudzidwa ndi kaphatikizidwe ka glycoproteins omwe amayendetsa ntchito ya autoimmune system. Kafukufuku wam'mbuyomu wachipatala awonetsa kuti mannose amatha kuchiza ndi kupewa matenda amkodzo, kotero kuti mankhwala ena akunja okhala ndi mannose monga chigawo chachikulu amagwiritsidwa ntchito kuti asunge thanzi la mkodzo. Mannitol ndi mowa wa shuga, womwe umachepetsedwa kuchokera ku shuga (mannose), ndi isomers wa sorbitol, wosungunuka m'madzi, ufa woyera wa crystalline, uli ndi kukoma kokoma kofanana ndi sucrose. Mannitol angagwiritsidwe ntchito osati monga kwambiri mafupa wothandizila, komanso monga lyophilized mapuloteni mtetezi mu malangizo ena. Kuteteza kwa mannitol pamapuloteni kumakhudzana ndi kukhazikika kwake komanso kapangidwe kake ka morphological, ndipo mayendedwe ake nthawi zina amagwirizana ndi crystal morphology. Nthawi zambiri amakhulupirira kuti amorphous mannitol imakhala ndi ntchito yokhazikitsira mapuloteni pomwe mannitol yonyezimira imataya ntchito yake yoteteza. Mannitol woipa wa 1% kapena zochepa kupewa kuphatikizika kwa mapuloteni mankhwala mwa mapangidwe amorphous nyumba, koma mkulu woipa wa mannitol amakonda crystallize ndi kulimbikitsa kaphatikizidwe mapuloteni mankhwala. Kwa mapuloteni ambiri, kusungidwa pa 4 ° C kumakhala kwakanthawi kochepa (pafupifupi sabata imodzi) mutayimitsidwanso. Posungira kwa nthawi yayitali, tikulimbikitsidwa kuti tikonzekere zosakaniza (zomwe ziyenera kukhala ndi mapuloteni onyamula, monga 0.1% BSA, 5%HSA, kapena 10% FBS) ndiyeno subpack itazizira pa -20 ℃ kapena -80 ℃. Ndikofunika kupewa kuzizira kobwerezabwereza ndi kusungunuka, chifukwa kuzizira ndi kusungunuka kulikonse kungayambitse kuchepa kwa mapuloteni. Trehalose ndi mannitol nthawi zambiri amawonjezeredwa ndi 8% (unyinji ndi voliyumu) ??ngati zoteteza zokongoletsedwa. Trehalose akhoza mwachionekere kuteteza yachiwiri dongosolo kusintha kwa mapuloteni ndi kutambasula ndi aggregation wa mapuloteni pa lyophilization. Mannitol amagwiritsidwanso ntchito lyophilized chitetezo ndi filler kuti akhoza kuchepetsa kudzikundikira ena mapuloteni pambuyo lyophilization. Chojambuliracho chimatha kupereka mawonekedwe oyenera a keke yowumitsidwa, kuthandizira mawonekedwe oyenera a keke yowuma-wouma, ndikupanga mawonekedwe a pore. Porosity ndizofunikira kuti madzi asungunuke, ndipo ma pores akuluakulu amatha kutsika mofulumira, kotero nthawi yoyamba yowumitsa imatha kuchepetsedwa. Kuphatikizika kwa zodzaza kumathandizira kuyanika kwakufupi koyambirira (kutentha kwazinthu Tp?Tg' kapena Tc) ndipo kutha kugwiritsidwa ntchito ngati njira yopititsira patsogolo njira ya biopharmaceutical lyophilization. Kawirikawiri chi?erengero cha stabilizer ku filler chiyenera kukhala osachepera 1: 2 kuti apereke crystallization yofunikira ya filler. The chifukwa latisi amapereka mawotchi thandizo kwa zigawo zikuluzikulu mu chikhalidwe chawo amorphous. Pamwamba pa Tg', dziko la amorphous lomwe limapangidwa ndi dongosolo lokonzekera silili lolimba mokwanira kuti lithandizire kulemera kwake ndipo lidzagwera pa intaneti ya crystal. Chifukwa cha chithandizo chamakina, kugwa kumatha kupewedwa ngakhale kuyanika kutentha kwambiri kuposa Tg' (kapena Tc). Pazakudya zokhala ndi zomanga thupi zochulukirapo kuposa 50 mg/mL, kuwonjezera ma fillers ndikofunikira kwambiri chifukwa Tg 'ya dongosolo imachulukitsidwa m'mapangidwe okhala ndi mapuloteni apamwamba kwambiri. Komabe, ngati filler imakhalabe amorphous pa nthawi ya lyophilization, kukhazikika kwa mapuloteni kungakhudzidwe chifukwa cha kuthekera kwa crystallization panthawi yosungirako, kotero kuti crystallization ya filler nthawi zambiri imalimbikitsidwa powonjezera sitepe ya annealing.