Isihloko
Indlela i-methylene blue ekhiqizwa futhi ihlanzwe ngayo
I-methylene blue yenziwa ngokuhlanganiswa kwamakhemikhali. Abakhiqizi bakha i-molecule kadayi, bayihlukanise nezinsalela zokusabela kwamakhemikhali, bahlukanise into edingekayo, bese behlola ikhwalithi yayo. Le misebenzi ihlukene: ukwenza ikhompawundi eluhlaza okwesibhakabhaka akufakazeli ukuthi iqoqo lihlangabezana nezimfuneko ezithile.
Ulwazi lwamakhemikhali olutholakala emphakathini luchaza ukuthi lokhu kungenziwa kanjani. Aluvezi indlela esetshenziselwe ibhodlela elithile. Ilungelo lobunikazi lichaza okusunguliwe nezibonelo zakho; irekhodi leqoqo lichaza okwenzeka ngesikhathi sokukhiqiza kwangempela.
I-methylene blue yenziwa ngani?
Incazelo ye-IARC yokukhiqizwa ngenjongo yokudayisa ichaza indlela esebenzisa ama-amine anesakhiwo esiyindilinga se-aromatic namaqembu afakwe esikhundleni samanye, okuhlanganisa i-N,N-dimethyl-p-phenylenediamine ne-N,N-dimethylaniline, kanye ne-sodium thiosulfate nezinto ezibangela i-oxidation. Ukusabela kwamakhemikhali kwakha uhlelo lwezindilinga eziqukethe isibabule lwe-methylene blue. Into eqediwe ivame ukuhlinzekwa njengosawoti we-chloride onamanzi ahambisana nento eqinile.
Lokhu ukuguqulwa kwamakhemikhali okuqala abe yinto entsha. Isithako esisetshenziswa ngesikhathi sokuhlanganisa asibi ngokuzenzakalelayo isithako sebhodlela eliqediwe. Ngakolunye uhlangothi, ukusibiza ngokuthi into yokuqala akufakazeli ukuthi izinsalela zaso zisusiwe. Imibuzo mayelana nenani lezinsalela idinga ubufakazi bokuhlaziywa.
Isahluko esifanayo se-IARC sichaza i-methylene blue eyomile njengamakristalu aluhlaza ngokumnyama noma impushana enamakristalu ecwebezela njengethusi, nakuba izixazululo zayo ziluhlaza okwesibhakabhaka ngokujulile. Akukho kulokhu kubukeka okufakazela ubumsulwa.
Izindlela ezishicilelwe ziyehluka ngezinto ezizifakayo
Indlela yendabuko ihlanganisa izingxenye zokwakha ze-aromatic bese ivala indilinga emaphakathi ngochungechunge lokusabela kwe-oxidation. Izinhlobo zayo ezisetshenziswa ezimbonini ziyehluka ngezinto ezibangela i-oxidation, ukuphathwa kwezinto eziphakathi nenqubo, nokuhlukaniswa komkhiqizo.
Ngokwesibonelo, i-US4212971A ichaza indlela ye-manganese dioxide eklanyelwe ukugwema i-dichromate ochungechungeni lwe-oxidation. I-copper sulfate nayo ibamba iqhaza enqubweni echaziwe. Lo mehluko ubalulekile ekuhleleni ikhwalithi: ukugwema isithako sokusabela esiqukethe i-chromium kushintsha omunye umthombo ongaba khona wokungcola, kodwa i-manganese nethusi kusadinga ukunakwa. “Inqubo engenayo i-dichromate” nokuthi “akukho ukungcola kwezakhi zamakhemikhali” kuyizimangalo ezihlukene.
Ezinye iziphakamiso ezintsha ziqala ngohlaka lwezindilinga oseluvele lukhona. I-WO2018167185A1 ichaza ukulungiswa okusekelwe ku-phenothiazine, kusetshenziswa ukufakwa kwama-halogen okulandelwa ukusabela ne-dimethylamine ukuze kutholakale udayi onamaqembu afakwe esikhundleni samanye. Lokhu kubonisa isu elihlukile lokuhlanganisa, hhayi ubufakazi bokuthi le ndlela isithathe indawo yokukhiqiza kwendabuko kuyo yonke indawo.
Ngokuvamile umthengi akakwazi ukuhlelela lezi zindlela ngokubaluleka esebenzisa amagama azo kuphela. Ukuqhathanisa okuwusizo ukubheka ukuthi inqubo ngayinye elawulwayo ikhiqiza yini ngokuphindaphindiwe into ehlangabezana nezimfuneko ezihlosiwe, okuhlanganisa nokungcola okuqondene naleyo ndlela.
Ukuhlanza kubhekana nezinhlobo ezahlukene zezinto ezisala zidlulela emkhiqizweni
Odayi abahlobene bayinselelo eyodwa. I-Azure A, i-Azure B ne-Azure C banezakhiwo ezisondelene ne-methylene blue. Ngakho ukuhlukanisa kungaba nzima kunokususa inhlayiya engahlobene engancibiliki. Isihlungi esihle singabamba izinhlayiya kuyilapho ukungcola kodayi okuncibilikile kudlula.
Inselelo yesibili yizinsalela eziqukethe izinsimbi. Eyesithathu yisincibilikisi senqubo esisala ngemva kokuhlukaniswa komkhiqizo. Isinyathelo sokuhlanza esinciphisa uhlobo olulodwa singashiya olunye lungashintshile kakhulu.
Izindlela ezimbili ezishicilelwe zibonisa lo mehluko:
- Ukuphuma kwento eqinile esixazululweni, ukukhishwa nokwakhiwa kwamakristalu. I-US12215234B2 ichaza ukususwa kwezinsimbi ngokuzikhipha njengezinto eziqinile ngesikhathi sokukhishwa ngesincibilikisi, okulandelwa ukuhlanzwa okwengeziwe nokuhlukaniswa komkhiqizo. Lo mbhalo uphinde uxhumanise izimo ze-alkaline nokwakheka kokungcola kodayi, futhi uxoxa ngokulawulwa kwe-pH nendlela ehlukile yokwakha amakristalu ukuze kususwe ukungcola okuyikhompawundi ye-organic. Lokhu kubonisa ukulinganiswa kwezinzuzo nezinkinga zenqubo: izimo eziwusizo ekuhlukaniseni kufanele zihlolwe nokuthi azibangeli yini ushintsho lwamakhemikhali olungafuneki. Ukusebenza okubikiwe kule ndlela kuqondene nezibonelo ezichaziwe, hhayi nayo yonke i-methylene blue edayiswayo.
- Ukuhlanza uhlobo olwenziwe i-reduction okwesikhashana. I-US20160200696A1 ichaza i-complex ezinzisiwe ye-leucomethylene blue efakwe i-proton. Inqubo yenza i-reduction ye-methylene blue, ihlanze leyo nto ephakathi nenqubo, bese iyibuyisela ngokuyenza i-oxidation. Inzuzo ehlongozwayo iwukuthi ukushintsha uhlobo lwamakhemikhali kwenza kube lula ukuyihlukanisa kodayi be-azure nasekungcoleni kwezinsimbi. “Leuco” ihlonza uhlobo olwenziwe i-reduction; yona ngokwayo ayisho ukuthi “imsulwa.”
Lezi zindlela zisebenzisa izici zamakhemikhali ezihlukene ukuze zifeze ukuhlukanisa. Ukuba khona kwazo kuchaza ukuthi kungani incazelo eyanele yenqubo inikeza ulwazi olungaphezu kwegama elithi “kuhlungiwe,” kodwa ayikho ethatha indawo yemiphumela yeqoqo langempela.
Umdwebo wenqubo: lapho kuvela khona imibuzo yekhwalithi
Ukuhlanganiswa kwemibono yezinqubo ezishicilelwe nezimiso zekhwalithi okuxoxwe ngazo lapha. Imicibisholo yemigqa eqhubekayo ibonisa ukuhamba kwezinto; imicibisholo yemigqa ephukile ihlobanisa izigaba nemibuzo yokuhlaziywa. Lezi akuzona izikhathi zokuthatha amasampula ezinqunyiwe, futhi ukuhlolwa kungase kusebenze ezigabeni eziningana. Izinto ezisusiwe ziyaphuma ngesikhathi sokuhlanza; ukuhlolwa kwaselabhorethri kukala lokho okusala.
Ithebula lixhumanisa leyo mibuzo nobufakazi obuwusizo. I-HPLC isho i-chromatography yoketshezi esebenza kahle kakhulu; i-IR isho i-spectroscopy ye-infrared; i-GC isho i-chromatography yegesi; i-ICP-MS isho i-mass spectrometry esebenzisa i-plasma ehlanganiswe ngokungeniswa kukagesi.
| Isigaba noma okukhathazayo | Okungadinga ukulawulwa | Ubufakazi obubhekana nakho |
|---|---|---|
| Amakhemikhali angenayo | Ubunjalo obungalungile, ikhwalithi eguquguqukayo noma ukungcola okungena nezinto ezisetshenziswayo | Izimfuneko zezinto ezingenayo, ukuhlolwa kobunjalo nokuhlolwa kokufaneleka kwabahlinzeki |
| Ukuhlanganiswa kwamakhemikhali | Odayi abahlobene, izinto zokuqala ezisele nezinto eziphakathi nenqubo | Izindlela ezifanele ze-chromatography ezinezinto ezihlosiwe ezihlonziwe, ukuzwela nemikhawulo yokwamukela |
| Izithako zokusabela eziqukethe izinsimbi | Izinsalela zezakhi zamakhemikhali ezidlulela ekuqhubekeni kwenqubo | Ukuhlaziywa okuqondene nezakhi ezithile, njenge-ICP-MS, okuhlanganisa iqoqo lezakhi okukhethwa kwazo kunesisekelo |
| Ukuhlukanisa okusebenzisa izincibilikisi nokomisa | Izinsalela zezincibilikisi zenqubo | Ukuhlolwa kwezincibilikisi nokuhlolwa okufanele kwezinsalela zazo, okuvame ukuba yi-GC |
| Isithako esihlukanisiwe | Ubunjalo obungalungile, inani elingalungile noma isisekelo samanzi esingalungile | Izindlela ezihambisanayo zokuhlonza, ukukala inani nokuhlolwa okufanele kwamanzi noma kokulahleka ngesikhathi sokomisa |
Lezi zindlela ziphendula imibuzo ehlukene. Incazelo ye-USP yokuhlolwa kwezinsalela zezincibilikisi ixoxa ngokuthi i-chromatography yegesi idingeka nini; ayithathi indawo yokuhlaziywa kodayi abahlobene. Ngokufanayo, ukukalwa kwezakhi zamakhemikhali akukwazi ukuhlonza odayi be-azure. Indlela kufanele ifanele into ehlolwayo. Umhlahlandlela wokungcola kwe-methylene blue nezindlela zokuhlola uchaza lo mehluko wokuhlaziywa ngokuningiliziwe.
Kungani iphesenti lokugcina lidinga umongo
Ukuhlolwa kwenani kukala inani lento ethile ngendlela echaziwe nangesisekelo esinqunyiwe sokubika. Indlela yokuhlola ukungcola ikala iqoqo elichaziwe lamanye amakhompawundi. Leyo miphumela ihlobene, kodwa ayikwazi ukusetshenziswa ngokushintshana.
Uhlaka lwezimfuneko lwe-ICH Q6A luhlukanisa ukuhlolwa kobunjalo, ukuhlolwa kwenani nokuhlolwa kokungcola. Luphinde lubhekane nokuhlolwa kwamanzi ezintweni ezimunca umswakama nakuma-hydrate. Entweni enamanzi aboshwe esakhiweni sayo, umphumela obikwe ngesisekelo sento eyomisiwe awukwazi ukufundwa njengephesenti lempushana njengoba yamukelwe ngaphandle kokucabangela leso sisekelo.
Umlando wenqubo wengeza olunye ungqimba. Isiqondiso se-ICH Q7 ngezithako ezisebenzayo zemithi sidinga iphrofayili yokungcola exhumene nenqubo yokukhiqiza elawulwayo, kanye nokuqhathanisa okungaveza izinguquko ezintweni ezingenayo noma ekukhiqizeni. Siphinde sicacise ukuhlonzwa kweqoqo, imikhawulo yokuhlola nemiphumela yezinombolo ezitifiketini zokuhlaziywa. Le mibhalo yesiqondiso yemithi ichaza izimiso zekhwalithi; ayinikezi umkhiqizo odayiswa ezitolo isimo sokuba umkhiqizo wemithi.
Lokhu kufakazelani nge-Blupreme?
Ulwazi lwekhwalithi olushicilelwe yi-Blupreme luchaza amarekhodi axhumanisa iqoqo lomkhiqizo webhodlela neqoqo lesithako se-methylene blue kanye nesitifiketi salo sokuhlaziywa. Leso isimangalo sokulandeleka. Asivezi indlela yokuhlanganisa yomkhiqizi wesithako, ukulandelana kwezinyathelo zokuhlanza noma izimo zokusebenza zefekthri.
Ngakho-ke, ayikho kulezi zindlela zamalungelo obunikazi ezingenhla okufanele ichazwe ngokuthi “indlela i-Blupreme eyenza ngayo i-methylene blue” ngaphandle kwemibhalo eyengeziwe yokukhiqiza. I-COA yesithako nayo ayikwazi, iyodwa, ukufakazela ukugxila kwesixazululo esiqediwe, ukusebenza kokupakisha noma ukungabi namagciwane. Lo mehluko uchazwe kokuthi i-COA yesithako uma iqhathaniswa nokuhlolwa komkhiqizo oqediwe.
Uma wenza isinqumo sokuthenga, qala ngeqoqo langempela nokusetshenziswa okudingekayo. Cela umbiko ohambisana nalo, uhlole izindlela nemikhawulo, bese ubuza ukuthi kulawulwa kanjani ukungcola kwenqubo okuqondene nalo. Uhlu lokuhlola lokuqhathanisa lomthengi we-methylene blue luguqula leyo mibuzo ibe indlela engaguquguquki yokuqhathanisa abahlinzeki.