Azure B: Umwanda, Metabolite n'Ubushakashatsi

Azure B ni ikinyabutabire gitandukanye na methylene blue ariko bifitanye isano ya hafi. Gishobora kuba gisanzwe kiri mu rugero rwa methylene blue, kikagaragara nyuma y'uko umubiri utunganyije methylene blue, cyangwa kigatangwa ukwacyo kugira ngo gikoreshwe mu igerageza. Ibi bisobanuro ntibivuguruzanya. Bisobanura aho icyo kinyabutabire cyaturutse n'icyo umushakashatsi ashaka kumenya kuri cyo.

Iri tandukaniro ni ingenzi mu gusobanura icyemezo cy'isesengura cyangwa amagambo avuga ku gikorwa cy'ikinyabuzima. Kwita Azure B metabolite ikora ntibituma ingano yayo itagenzurwa iri mu icupa iba yifuzwa. Kuyita umwanda na byo ntibisobanura ko idakora mu binyabuzima.

Ni iki gihinduka mu rwego rw'ikinyabutabire?

Azure B ni derivative ya methylene blue yakuweho methyl imwe. Itsinda rimwe rya methyl ryari rifatanye na nitrogen ryasimbujwe hydrogen. Iyi sano isobanurwa mu biganiro ku miterere y'ikinyabutabire no muri Figure 1 y'isuzuma rya Schirmer na bagenzi be. Ni ihinduka ryihariye ry'imiterere y'ikinyabutabire, si irindi zina rya methylene blue.

Ibi kandi bitandukanye no kugabanywa kwa methylene blue ikaba leucomethylene blue. Reduction ihindura oxidation state; N-demethylation yo ihindura substituent iri kuri nitrogen. Gufata izi nzira zombi nk'aho ari “methylene blue ihinduka idafite ibara” gusa bitakaza itandukaniro rikenewe mu gusobanura metabolism. Amazina y'amarangi afitanye isano na yo agomba kwitonderwa kimwe: Azure A, Azure B, na methylene blue si amazina ashobora gusimburana. Ubuyobozi ku binyabutabire bifite amazina asa busobanura icyo kibazo cy'amazina.

Inkomoko eshatu, ibibazo bitatu bitandukanye

Igishushanyo cyo ku gifuniko gitandukanya inzira eshatu zishobora gukurikizwa mu iperereza. Imbonerahamwe igaragaza neza ibimenyetso bikenewe kuri buri nzira.

Aho Azure B yinjirira mu iperereza	Ikibazo kibazwa	Ibimenyetso bifite akamaro	Umwanzuro udakwiye gukurwamo
Isanzwe iri mu bikoresho byatangiriweho	Iyi batch irimo iki?	Uburyo butandukanya kandi bugapima ingano ya Azure B, buhujwe na lot kandi bukurikiza specification ikoreshwa	Ingano yabonetse ituma ingaruka z'igicuruzwa zirushaho kuba nziza
Ibonetse nyuma yo guhura na methylene blue	Ni ibihe binyabutabire biboneka uko igihe kigenda?	Isesengura ry'ibikoresho byatangiriweho hamwe n'ibipimo by'ibinyabuzima bikurikirana, byemejwe	Buri molecule yabonetse igomba kuba yarakorewe mu mubiri
Yongewe nk'ikinyabutabire cyasobanuwe ukwacyo	Azure B ubwayo ikora iki?	Kumenya icyo ari cyo, ubuziranenge, concentration, comparator, n'endpoint y'igerageza yasobanuwe	Ingaruka imwe iba no ku barwayi bafata methylene blue

Umurongo wo hagati ushobora kwirengagizwa byoroshye. Niba Azure B yari isanzwe iri mu kinyabutabire cyatanzwe, urugero rw'ikinyabuzima rufashwe nyuma rushobora kuba rurimo Azure B yari isanzwe ihari hamwe n'iyakozwe nyuma. Kwemeza ko yakozwe mu mubiri bisaba ibirenze kubona peak nyuma yo guhura na methylene blue.

Azure B mu bikoresho byatangiriweho

Ubushakashatsi bw'isesengura bwo hambere butanga urugero rwiza rw'impamvu ikinyabutabire kiri ku rugero ruto gishobora kuba ingenzi. Abashakashatsi basuzumaga iodination ya methylene blue bakoresheje HPLC–mass spectrometry basanze igicuruzwa nyamukuru cyari cyashyizwemo iodine cyaturukaga ku mwanda wa Azure B. Ingero za methylene blue zasuzumwe zari zirimo hafi 7–8% Azure B. Mu mimerere y'iyo reaction, Azure B yashyizwemo iodine yari nyinshi cyane kurusha methylene blue yashyizwemo iodine.

Izo percentages zisobanura ibikoresho byakoreshejwe muri ubwo bushakashatsi bwo mu 1999. Ntizigaragaza urugero rw'umwanda rwemewe uyu munsi cyangwa ibigize igicuruzwa cy'undi mutanga. Iryo gerageza rigaragaza ingingo yihariye: ikinyabutabire cyinshi kurusha ibindi mu byo batangiranye si ko buri gihe gitanga igicuruzwa cya reaction kiba kinini kurusha ibindi.

Ku cyemezo cy'isesengura, suzuma igisubizo cya Azure B by'umwihariko, units, uburyo bwo gupima, reporting limit, n'umwirondoro wa lot. Total dye assay na related-substances test bisubiza ibibazo bitandukanye. Igisubizo cya “ntiyabonetse” na cyo gisaba detection cyangwa reporting limit kugira ngo gishobore gusobanurwa. Reba uburyo bwo gusoma icyemezo cy'isesengura cya methylene blue kugira ngo ubone ibindi bigomba kugenzurwa muri iyo nyandiko.

Azure B ikorwa mu gihe cya metabolism

Kwiga metabolism bisaba uburyo bw'isesengura butandukanya ikinyabutabire cy'ibanze na metabolite yacyo. Kim na bagenzi be bakoze uburyo bwa LC–MS/MS bwo gupima ibinyabutabire byombi muri plasma y'imbeba. Calibration range yabo yari 1–1,000 ng/mL kuri buri kinyabutabire, bafite lower quantification limit ya 1 ng/mL bakoresheje 20 microlitres za plasma y'imbeba. Hanyuma bakoresheje ubwo buryo mu bushakashatsi bwa pharmacokinetics ku mbeba.

Ibi bisobanuro ni ingenzi kuko uburyo bwo gupima bugira ubwoko bw'urugero bwagenewe. Validation yakozwe muri plasma y'imbeba ntiyemeza mu buryo bwikora ko ubwo buryo ari nyabwo muri plasma y'umuntu, urine, cyangwa solution y'ubucuruzi ifite concentration nyinshi. Ubu buryo bwerekana uko abashakashatsi bashobora gukurikirana ibinyabutabire bibiri ukwabyo; ntibutanga itegeko ryo kugena dose ku bantu.

Amakuru yo ku guhura kw'abantu n'ibi binyabutabire na yo agaragaza impamvu percentage imwe idahinduka ya metabolite idahagije. Igice cya clinical pharmacology cyo ku kirango cy'umuti wa methylene blue uterwa kivuga ko exposure ya Azure B yiyongereye ku bitabiriye ubushakashatsi bari bafite renal impairment. Exposure uko igihe kigenda igaragaza ikorwa ry'ikinyabutabire, uko gikwirakwira, n'uko gisohorwa, aho kugaragaza gusa ibigize ibiri mu icupa. Route, igihe urugero rwafatiwe, n'aho mu mubiri hapimwe byose ni ingenzi mu kugereranya ibi bisubizo.

Icyo amagerageza ataziguye agaragaza

Azure B ifite pharmacological activity ipimika. Ikibazo gifite akamaro kurushaho ni target ikoraho n'imimerere ikoreramo.

Mu bushakashatsi bwo mu 2012 bwakoresheje recombinant human monoamine oxidase, Azure B yabujije MAO-A gukora ifite IC50 ya 11 nM, ugereranyije na 70 nM kuri methylene blue mu mimerere imwe. IC50 ni concentration ijyanye na 50% inhibition muri iyo assay. Azure B yanabujije MAO-B gukora, ariko kuri concentration iri hejuru cyane: 968 nM. Abashakashatsi bavuze ko inhibition yashoboraga gusubira inyuma.

Ibi bisubizo bishyigikira ko Azure B ishobora kugira uruhare mu ngaruka z'ibinyabuzima no mu mikoranire y'ibinyabutabire, harimo n'ibibazo bijyanye na methylene blue na neurotransmitters. Ntibisobanura ko Azure B ari umuti mwiza inshuro esheshatu. Iyo ratio isobanura inhibition ya enzyme imwe mu igereranya rimwe ry'igerageza.

Irindi gerageza ryihariye rya cholinesterase y'umuntu rigaragaza imipaka yo gukwirakwiza uwo mwanzuro. IC50 za Azure B zari 0.486 micromolar kuri acetylcholinesterase na 1.99 micromolar kuri butyrylcholinesterase. Methylene blue yari ifite potency nyinshi muri izo assays, ifite agaciro ka 0.214 na 0.389 micromolar uko zikurikirana. Uko byakurikiranye byarahindutse bitewe na biological target. Nta na kimwe muri ibyo bisubizo cyonyine cyemeza ko cognition irushaho kuba nziza cyangwa ko Alzheimer's disease ivurwa.

Kuva ku gikorwa cy'igerageza kugera ku busobanuro bwa clinical

Amagerageza akorerwa ku nyamaswa nzima atanga urundi rwego rw'ibimenyetso ariko ntiyemeza clinical efficacy. Mu bushakashatsi bwa Delport na bagenzi be ku mbeba, Azure B yagabanyije immobility mu acute forced-swim test, aho methylene blue na imipramine byari bimwe mu byakoreshwaga mu kugereranya. Inyandiko y'ubushakashatsi ibyita antidepressant-like effect. Ryari igerageza ry'imyitwarire ku mbeba, si trial ipima uko abarwayi bakira depression.

Ku kintu icyo ari cyo cyose kivugwa kuri Azure B, banza umenye ibikoresho byapimwe. Hanyuma umenye organism cyangwa assay, exposure, na endpoint. Hanyuma urebe niba umwanzuro werekeye ibigize ikintu, metabolism, enzyme activity, imyitwarire y'inyamaswa, cyangwa clinical benefit. Izi ntambwe zituma igisubizo kijyanye n'ubuziranenge bwa batch kititiranywa n'amagambo avuga ku kuvura, kandi zigatuma mechanism yagaragajwe mu igerageza ititiranywa n'ibisubizo byemejwe ku barwayi.