0102030405
I-Mannose ne-Mannitol
2025-03-21
- Ukomisa iqhwa, okubizwa ngokuthi ukomisa iqhwa, kuyindlela yokomisa eqandisa ngaphambili isixazululo somuthi esidinga ukomiswa sibe esiqinile bese sinciphisa ngokuqondile amanzi asuka endaweni eyiqhwa ngaphandle kokudlula esimweni esiwuketshezi ngaphansi kwezinga lokushisa eliphansi nezimo zengcindezi ephansi. Ngenxa yokuthi yonke inqubo yokusebenza isesimweni sokushisa esiphansi, le ndlela ifaneleka ngokukhethekile ukulungiswa kwamalungiselelo ezidakamizwa ezizwela ukushisa amaprotheni. Umuthi weprotein omisiwe ube yiqhwa wawuxega njengekhekhe, owawungagcini nje ngokugcina ukulondoloza kodwa futhi ube nomthelela ekuvuselelekeni komuthi wamaprotheni ngemva kokuhlakazwa kabusha. Ngokusobala, ubuchwepheshe bokumisa iqhwa bunikeza indlela ephumelelayo yokulungiselela amaprotheni amalungiselelo emithi enezakhiwo ezingazinzile zomzimba namakhemikhali. Kodwa-ke, inqubo yokumisa iqhwa iyinqubo yenguquko yesigaba esiyinkimbinkimbi, futhi kunezici eziningi ezenza amaprotheni denaturation ngesikhathi sokuqandisa, ukuncibilika kweqhwa, ukomisa nokugcinwa, ngakho-ke amanye ama-agent avikelayo avame ukusetshenziselwa ukuzinzisa amaprotheni encwadini kadokotela. Ushukela, i-excipient evame ukusetshenziswa kakhulu emikhiqizweni eqandisiwe, iqembu le-hydroxyl esakhiweni salo lingashintsha isibopho se-hydrogen phakathi kwamaprotheni namanzi ukuze sinikeze umphumela ozinzile, i-stabilizer engaqondile yamaprotheni, futhi ingadlala indima ethile yokuzivikela ezigabeni ezihlukahlukene zokumisa iqhwa (njengokuqhwaza, ukumisa iqhwa, ukuncibilika, njll.). Umthelela wokuvikela ushukela uhlobene nohlobo lwamaprotheni nama-disaccharides, futhi ama-disaccharides yiwona asetshenziswa kakhulu futhi aqashelwa ukuthi avikeleke kakhulu. I-Sucrose iyi-disaccharide eyakhiwe i-molecule eyodwa ye-glucose ne-molecule eyodwa ye-fructose, eqinile kumakhemikhali futhi ikakhulukazi inesakhiwo se-amorphous, futhi idlala indima ebalulekile ekuvimbeleni ukuguqulwa kwesakhiwo sesibili samaprotheni, nokwandiswa nokuhlanganiswa kwamaprotheni ngesikhathi se-lyophilization nokugcinwa. Uma kuqhathaniswa ne-sucrose, i-trehalose inezinga lokushisa eliphakeme lokushintsha kwengilazi, ukungeniswa komswakama okuphansi, kanye nokuncishiswa okuncane. Lezi zinzuzo zibonisa ukuthi i-trehalose ingaba nethuba elibanzi lohlelo lokusebenza. Uphuzo oludakayo, olufana ne-mannitol, luvame ukusetshenziswa njengezigcwalisi ezicwebezela lapho kubanda kancane ukuze kuhlinzekwe isakhiwo esisekela ingxenye esebenzayo futhi akusabeli ngaso.
I-Mannose iyi-monosaccharide, encibilika emanzini, encibilika kancane ku-ethanol. I-crystalline powder engenambala noma emhlophe. Idlala indima ebalulekile kumetabolism yomuntu, ikakhulukazi kunqubo ye-glycosylation yamaprotheni athile. Kunzima ukuthi i-mannose imunce umzimba womuntu, futhi izokhishwa ngumzimba womuntu ngokushesha ngemva kokuyidla, ikakhulukazi nge-metabolism yezinso, futhi umjikelezo womzimba wonke cishe amahora ayisishiyagalombili. Ukudla i-mannose akukubangeli ukunyuka kukashukela egazini, ngakho kuwuhlobo lukashukela olungadliwa abanye abantu abanesifo sikashukela. Ngokwemvelo, i-mannose ikhona esimweni esikhululekile kwezinye izithelo, njengama-cranberries, ama-apula, amawolintshi, njll. Emzimbeni womuntu, i-mannose isakazwa kuzo zonke izicubu negazi, okuhlanganisa isikhumba, izitho nezinzwa. Kulezi zicubu, i-mannose ihileleke ekuhlanganiseni ama-glycoprotein alawula umsebenzi wesistimu ye-autoimmune. Ucwaningo lwangaphambili lwezokwelapha luye lwabonisa ukuthi i-mannose ingakwazi ukwelapha futhi ivimbele izifo ze-urinary tract, ngakho-ke eminye imikhiqizo yezempilo yangaphandle ene-mannose njengengxenye eyinhloko isetshenziselwa ukugcina impilo yesistimu yomchamo. I-Mannitol iwutshwala obushukela, ngokuvamile obuncishisiwe kusuka kushukela (mannose), iyisomers ye-sorbitol, encibilika emanzini, i-white crystalline powder, inokunambitheka okumnandi okufana ne-sucrose. I-Mannitol ingasetshenziswa hhayi nje njenge-ejenti enhle kakhulu yamathambo, kodwa futhi njengesivikeli seprotheyini e-lyophilized kweminye imiyalelo. Umthelela wokuvikela we-mannitol kumaprotheni uhlobene nokugxila kwayo kanye nesakhiwo se-morphological, futhi ukugxila kwayo ngezinye izikhathi kuhlobene ne-crystal morphology. Ngokuvamile kunenkolelo yokuthi i-amorphous mannitol inomsebenzi wokuzinzisa amaprotheni kuyilapho i-mannitol ecwebezelayo ilahlekelwa umsebenzi wayo wokuvikela. Ukugxiliswa kwe-Mannitol okungu-1% noma ngaphansi kuvimbela ukuhlanganiswa kwezidakamizwa zamaprotheni ngokwakhiwa kwezakhiwo ze-amorphous, kodwa ukugxila okuphezulu kwe-mannitol kuvame ukucwebezela futhi kukhuthaze ukuhlangana kwezidakamizwa zamaprotheni. Kumaprotheni amaningi, ukulondolozwa ku-4 ° C kungokwesikhashana (cishe isonto eli-1) ngemuva kokumiswa kabusha. Ukugcina isikhathi eside, kuyanconywa ukuthi kulungiswe izixuku (okumele ziqukathe amaprotheni enkampani yenethiwekhi, afana no-0.1% BSA, 5%HSA, noma u-10% FBS) bese iphakethe elincane liqandiswe ku -20℃ noma -80℃. Kubalulekile ukugwema ukubanda nokuncibilika okuphindaphindiwe, njengoba ukuqhwa nokuncibilika ngakunye kuzobangela ukungasebenzi ngokwengxenye kwamaprotheni. I-Trehalose kanye ne-mannitol kuvame ukwengezwa ngo-8% (ubuningi ngevolumu) njengezivikeli ezi-lyophilized. I-Trehalose ngokusobala ingavimbela ukuguqulwa kwesakhiwo sesibili samaprotheni kanye nokwelula nokuhlanganiswa kwamaprotheni ngesikhathi se-lyophilization. I-Mannitol nayo iyisivikelo se-lyophilized esisetshenziswa kakhulu futhi isigcwalisi esinganciphisa ukuqoqwa kwamaprotheni athile ngemuva kwe-lyophilization. I-filler ingahlinzeka ngesakhiwo esifanele sekhekhe elomisiwe, ifake isandla ekubunjweni okufanele kwebhulokhi yekhekhe efriziwe, futhi yakha isakhiwo se-pore. I-Porosity iyisidingo sokuqala sokuncishiswa kwamanzi ayiqhwa, futhi izimbotshana ezinkudlwana zingancipha ngokushesha, ngakho-ke isikhathi sokuqala sokumisa singancishiswa. Ukwengezwa kwezigcwalisi kuvumela ukomisa okuyisisekelo okufushane (izinga lokushisa lomkhiqizo Tp?Tg' noma Tc) futhi kungasetshenziswa njengendlela yokuthuthukisa inqubo ye-biopharmaceutical lyophilization. Imvamisa isilinganiso se-stabilizer ne-filler kufanele okungenani sibe ngu-1:2 ukuze sinikeze ukucwebezela okudingekile kokugcwalisa. I-lattice ewumphumela inikeza ukusekelwa kwemishini kwezingxenye esimweni sazo se-amorphous. Ngenhla kwe-Tg', isimo se-amorphous esakhiwe uhlelo lokulungiselela asiqinile ngokwanele ukusekela isisindo saso futhi sizowela kunethiwekhi yekristalu. Ngenxa yokusekelwa komshini, ukuwa kungavinjelwa naphezu kwamazinga okushisa omile angaphezu kwe-Tg' (noma i-Tc imbala). Ekwakheni okune-protein concentrations