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IMannose kunye neMannitol

2025-03-21

  1. Umkhenkce-ukomisa, obizwa ngokuba ngumkhenkce-womisa, yindlela yokomisa ebeka kwangaphambili isisombululo sechiza esifuna ukusomiswa sibe siqina kwaye sithobe ngokuthe ngqo amanzi avela kwimo engumkhenkce ngaphandle kokudlula kwimeko yolwelo phantsi kobushushu obuphantsi kunye neemeko zoxinzelelo oluphantsi. Ngenxa yokuba yonke inkqubo yokusebenza ikwimeko yobushushu obuphantsi, le ndlela ifaneleke ngokukodwa ukulungiselela amalungiselelo eziyobisi ezingeva lubushushu. Ichiza leprotein eyomisiweyo elinomkhenkce lalikhululekile njengekeyiki, elalingancedi nje kuphela ekugcinweni kodwa likwanceda ekukwazini ukuphinda kusebenze ichiza leprotein emva kokuchithwa kwakhona. Ngokucacileyo, itekhnoloji yokumisa umkhenkce ibonelela ngendlela esebenzayo yokulungiselela iprotein yamalungiselelo amayeza aneempawu ezingazinzanga zomzimba kunye neekhemikhali. Nangona kunjalo, inkqubo yokumisa umkhenkce yinkqubo yokuguquka kwesigaba esiyinkimbinkimbi, kwaye kukho izinto ezininzi ezibangela iprotheni denaturation kwinkqubo yokukhenkceza, i-freeze-thawing, ukomisa kunye nokugcinwa, ngoko ke ezinye ii-arhente zokukhusela zihlala zisetyenziselwa ukuzinzisa iprotheni kwi-prescription. Iswekile, i-excipient esetyenziswa ngokuqhelekileyo kwimveliso eyomileyo, iqela le-hydroxyl kwisakhiwo salo lingathatha indawo yebhondi ye-hydrogen phakathi kweprotheni kunye namanzi ukubonelela ngefuthe elizinzileyo, i-stabilizer engabonakaliyo yeprotheni, kwaye inokudlala indima ethile yokukhusela kwizigaba ezahlukeneyo zokumisa umkhenkce (njengokukhenkceza, ukucima ukuqhaqha, ukunyibilika, njl njl). Isiphumo sokukhusela iswekile sinxulumene nohlobo lweprotheyini kunye ne-disaccharides, kwaye i-disaccharides yiyona nto ifundwayo kwaye ibonwa njengeyona ndlela ikhuselekileyo yokukhusela. I-Sucrose yi-disaccharide eyenziwe yi-molecule enye ye-glucose kunye ne-molecule enye ye-fructose, ezinzileyo kwiikhemikhali kwaye ininzi inesakhiwo se-amorphous, kwaye idlala indima ebalulekileyo ekuthinteleni ukuguqulwa kwesakhiwo sesibini seeprotheni, kunye nokwandiswa kunye nokuhlanganiswa kweeprotheni ngexesha le-lyophilization kunye nokugcinwa. Xa kuthelekiswa ne-sucrose, i-trehalose inobushushu obuphezulu beglasi yokutshintsha, ukungeniswa kokufuma okusezantsi, kunye nokuncipha okuncitshisiweyo. Ezi zibonelelo zibonisa ukuba i-trehalose inokuba nethemba elibanzi lokusetyenziswa. Utywala, obufana ne-mannitol, busetyenziswa ngokuqhelekileyo njengezigcwalisi ezicwebezelayo ekukhenkceni okucothayo ukubonelela ngesakhiwo esixhasayo secandelo elisebenzayo kwaye musa ukusabela ngalo.
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    I-Mannose yi-monosaccharide, i-soluble emanzini, i-soluble kancinane kwi-ethanol. I-crystalline powder engenambala okanye emhlophe. Idlala indima ebalulekileyo kwi-metabolism yabantu, ngakumbi kwinkqubo ye-glycosylation yeeprotheni ezithile. Kunzima ukuba i-mannose ifunxwe ngumzimba womntu, kwaye iya kukhutshelwa ngumzimba womntu ngokukhawuleza emva kokuyitya, ngokukodwa ngokusebenzisa i-metabolism yezintso, kwaye umjikelo we-metabolic uphelele malunga neeyure ezisibhozo. Ukutyiwa kwemannose akukwenzi ukuba iswekile inyuke, ngoko luhlobo lweswekile olunokutyiwa ngabanye abantu abanesifo seswekile. Ngokwendalo, i-mannose ikhona kwindawo ekhululekile kwezinye iziqhamo, ezifana ne-cranberries, ii-apula, ii-oranges, njl. Emzimbeni womntu, i-mannose isasazwa kuzo zonke izicubu kunye negazi, kubandakanywa ulusu, izitho kunye nemithambo-luvo. Kwezi zicubu, i-mannose ibandakanyeka kwi-synthesis ye-glycoprotein elawula umsebenzi we-autoimmune system. Izifundo zeklinikhi zangaphambili zibonise ukuba i-mannose inokunyanga kwaye ithintele usulelo lwe-urinary tract, ngoko ke ezinye iimveliso zempilo zangaphandle kunye ne-mannose njengenxalenye ephambili zisetyenziselwa ukugcina impilo ye-urinary system. I-Mannitol yi-alcohol yeswekile, edla ngokuncitshiswa kwiswekile (mannose), i-isomers ye-sorbitol, i-soluble emanzini, i-white crystalline powder, inencasa eswiti efana ne-sucrose. I-Mannitol ingasetyenziselwa kuphela njenge-agent egqwesileyo yamathambo, kodwa kunye nomkhuseli weprotheni ye-lyophilized kwezinye imimiselo. Impembelelo yokukhusela ye-mannitol kwiprotheni ihambelana nokugxininiswa kwayo kunye nesakhiwo se-morphological, kwaye ukugxininiswa kwayo ngamanye amaxesha kuhambelana ne-crystal morphology. Ngokuqhelekileyo kukholelwa ukuba i-amorphous mannitol inomsebenzi wokuzinzisa iprotheni ngelixa i-mannitol eyikristale ilahlekelwa ngumsebenzi wayo wokukhusela. I-Mannitol concentrations ye-1% okanye ngaphantsi ithintela ukuhlanganiswa kwamachiza eprotheni ngokuqulunqwa kwezakhiwo ze-amorphous, kodwa ukugxila okuphezulu kwe-mannitol kuthande ukucwebezela kwaye kukhuthaze ukuhlanganiswa kwamachiza eprotheni. Kwiiprotheyini ezininzi, ukugcinwa kwi-4 ° C lixesha elifutshane kuphela (malunga neveki ye-1) emva kokumiswa kwakhona. Ukugcina ixesha elide, kuyacetyiswa ukuba kulungiswe izinyibilikisi (ekufuneka ziqulathe iiproteni ezithwalayo, ezifana ne-0.1% BSA, 5%HSA, okanye i-10% FBS) emva koko i-subpack ikhenkcezwe ku -20℃ okanye -80℃. Kubalulekile ukuphepha ukukhenkceza okuphindaphindiweyo kunye nokunyibilika, njengoko ukukhenkceza kunye nokunyibilika ngalunye kuya kubangela ukungasebenzi kweprotheni. I-Trehalose kunye ne-mannitol zihlala zongezwa nge-8% (ubunzima ngomthamo) njengezikhuseli ezi-lyophilized. I-Trehalose inokuthintela ngokucacileyo utshintsho lwesibini lwesakhiwo seprotheni kunye nokwelula kunye nokuhlanganiswa kweeprotheni ngexesha le-lyophilization. I-Mannitol iphinda isetyenziswe ngokubanzi i-lyophilized ukukhusela kunye nokuzalisa oko kunokunciphisa ukuqokelela kweeprotheni ezithile emva kwe-lyophilization. I-filler inokubonelela ngesakhiwo esifanelekileyo sekhekhe elomileyo, igalelo kwimilo efanelekileyo yebhloko yekhekhe eyomileyo, kwaye yenza isakhiwo se-pore. I-Porosity iyimfuneko yokuthotywa kwamanzi angumkhenkce, kwaye iipores ezinkulu zinokuthoba ngokukhawuleza, ngoko ke ixesha lokuqala lokumisa lingancitshiswa. Ukongezwa kwezihluzi kwenza ukomisa okuphambili okufutshane (ubushushu bemveliso Tp?Tg' okanye Tc) ixesha kwaye ingasetyenziswa njengendlela yokwandisa inkqubo yebiopharmaceutical lyophilization. Ngokuqhelekileyo umlinganiselo we-stabilizer kwi-filler kufuneka ubuncinane ube yi-1: 2 ukubonelela nge-crystallization efunekayo yokugcwalisa. I-lattice ephumelayo ibonelela ngenkxaso yomatshini kumacandelo kwimeko yabo ye-amorphous. Ngaphezulu kwe-Tg', i-amorphous state eyenziwe yinkqubo yokulungiselela ayiqini ngokwaneleyo ukuxhasa ubunzima bayo kwaye iya kuwela kwi-crystal network. Ngombulelo kwinkxaso yomatshini, ukuwa kunokuthintelwa nangona amaqondo okushisa omile aphezulu kune-Tg' (okanye i-Tc). Ekuqulunqweni kunye neeprotheyini ze-protein