Amateka ya methylene blue: kuva ku rangi kugeza ku muti no ku bushakashatsi

Methylene blue yageze ku murwayi mbere y'uko igera muri farumasi.

Raporo yo mu 1891 ya Paul Guttmann na Paul Ehrlich ku ikoreshwa ry'irangi muri malaria irimo ibishushanyo bibiri by'ubushyuhe bw'umubiri. Icya kabiri gitangira ku wa 13 Nyakanga kikagera ku wa 5 Kanama, kandi ku ruhande handitswe uko ubuvuzi bwatanzwe umunsi ku wundi. Ibyanditswe ku wa 18 na 19 Nyakanga bigira biti "1 × 0,05 Methylenblau". Mu minsi yakurikiyeho handitswe inshuro eshanu n'indwi z'ingano imwe, kandi ku wa 22 Nyakanga hongewemo kinine nkeya. Umurongo w'ubushyuhe, uhindagurika hagati ya 37 °C na 39.5 °C mu gice cya mbere cy'igishushanyo, uraringanira nyuma y'uko irangi ritangiye gutangwa kandi ukaguma hagati ya hafi 36 °C na 37.5 °C mu byumweru bitatu bisigaye.

Umurwayi yari umwe muri babiri, basobanuwe muri iyo nyandiko nk'umukozi wo mu rugo n'umusare. Uru ruvange bari bahawe rwari rumaze imyaka cumi n'itanu rugurishwa nk'irangi ry'imyenda, kandi abo bagabo bombi bari mu bantu ba mbere banditswe ko bavuwe n'umuti wakozwe mu buryo bwa sintetike wose ugenewe ikinyabuzima runaka.

Irangi ni ryo ryabanje

Irangi rya mbere rya sintetike ryageze ku ntsinzi mu bucuruzi ryakozwe na William Henry Perkin mu 1856. Perkin yari afite imyaka cumi n'umunani, yakoreraga muri laboratwari yo mu rugo mu kiruhuko cya Pasika, kandi yageragezaga gukora kinine mu buryo bwa sintetike. Ahubwo yabonye ibisigazwa by'umukara, arabishongesha, maze abona ibara ryafataga kuri silike mu buryo bwiza cyane. Yarifatiye patanti muri Kanama 1856, kandi mu mpera za 1857 yari amaze kugira uruganda rwagezaga irangi ku ruganda rwo gusiga silike i Londres.

Mu 1875 Adolf von Baeyer yakoze irangi ritukura mu buryo bwa sintetike aryita eosin, rikomoka kuri Eos, ijambo ry'Ikigereki risobanura umuseke. Mu 1876 Heinrich Caro, wari umuyobozi wa laboratwari ya Badische Anilin- und Soda-Fabrik icyo gihe, yateje imbere methylene blue afatanyije na Baeyer nk'irangi rishingiye kuri aniline rigenewe ipamba. Imiterere yayo ya shimi ntiyemejwe neza kugeza hafi imyaka icyenda nyuma yaho.

Iyo nkomoko iracyagaragara mu buryo icyo kinyabutabire cyitwa. "Methylene blue" ni izina ry'ubucuruzi ryaturutse muri kataloge y'amabara, si ibisobanuro bya shimi. Uruvange iryo zina ryerekeza kuri rwo ni methylthioninium chloride, kandi itandukaniro hagati y'izina, umunyu waryo, na hydrates zaryo ritangira kugira akamaro igihe umuntu apima icyo kinyabutabire cyangwa asoma ibisabwa ku bwiza bwacyo.

Gusiga ingirabuzimafatizo byabaye ikiraro

Inzira yavanye irangi mu nganda ikarigeza mu bitaro yanyuze muri microscope, kandi yatangiye mbere y'uko methylene blue ibaho. Wilhelm Erb ni we muntu wa mbere wakoresheje irangi rya sintetike ku maraso, akoresha picric acid mu 1865, maze abona imiterere imeze nk'urusobe imbere muri zimwe mu ngirabuzimafatizo zitukura.

Mu nyandiko ye y'ikirenga ya 1878, Paul Ehrlich yagereranyije gusiga ingirangingo mu bushakashatsi n'ikoreshwa ry'amabara ku myenda, avuga ko byombi ari imikoranire ya shimi. Akorana na Robert Koch kuri bacillus itera igituntu, yashyize amabara ya aniline mu byiciro bya acid n'ibya basic kandi agaragaza ko buri cyiciro cyasigaga ibice bitandukanye by'ingirabuzimafatizo. Mu 1880 yabivanze byombi: umuti wuzuye wa methylene blue wasukwaga muri acid fuchsin kugeza igice cy'amazi cyo hejuru kibaye kibonerana. Icyavuyemo, yise neutralen Farbkörper cyangwa irangi ridafite uruhande rwa acid cyangwa basic, cyatangaga amabara atatu aho gutanga rimwe, kigaragaza udukomatanyabice two mu ngirabuzimafatizo za polymorphonuclear tutari twarigeze tugaragara mbere, kandi kigatuma bishoboka bwa mbere kubara ubwoko butandukanye bwa leukocytes. Kubera ko utwo dukomatanyabice twafataga ibice byombi by'uruvange, Ehrlich yahimbye ijambo neutrophil kuri izo ngirabuzimafatizo twabagamo.

Imyaka ibiri nyuma yaho Koch yakoresheje methylene blue kugira ngo abone bacillus itera igituntu, kandi mu 1883 Ehrlich anonosora ubwo buryo. Mu 1886 yatangaje ubundi bwoko bw'ubushakashatsi: yateye irangi mu nyamaswa zikiri nzima, agereranya uburyo buri rugingo rwarifata, maze asoza avuga ko ryagaragazaga gukunda cyane ingirangingo z'ubwonko n'imyakura. Yavuze ko ibyo byaterwaga n'izunguruka rya oxidation-reduction ry'irangi, yari yarabonye umwaka wabanje. Iryo zunguruka ni na ryo rituma umuti wa methylene blue utakaza ibara iyo oxygen iwurimo ikoreshejwe, maze ukarisubirana igihe umwuka ugarutse. Ubushakashatsi bwa mbere bwapimye ingaruka z'iryo zunguruka ni ubw'ikindi gihe cyakurikiyeho, kandi uburyo ubwabwo bukora ni ingingo itandukanye n'amateka yabwo.

Parasite na nucleus y'umutuku

Alphonse Laveran yavumbuye parasite ya malaria mu 1880 asuzuma amaraso mashya atarasizwe irangi. Kuyibona buri gihe muri smear yumye byasabaga irangi, kandi amabara yakoreshwaga icyo gihe yatangaga umutuku n'ubururu gusa.

Mu 1888, umuhanga mu ndwara w'Umunyapolonye Czesław Cheçinski yasimbuje acid fuchsin eosin, akora uruvange rwa methylene blue na eosin. Uburyo bwe bwaturutse ku kibazo cy'umusirikare wari wapfuye azize malaria ku wa 30 Nzeri 1887. Mu mafoto y'amaraso Cheçinski yabonye imiterere y'ubururu imeze nk'indabo za daisy, ubu izwi nka Plasmodium malariae, n'imiterere imeze nk'umuhoro, ubu izwi nka gametocytes za Plasmodium falciparum. Ibyavuye muri ubwo bushakashatsi byarangije ibisobanuro bibiri byari bihanganye ku cyateraga indwara icyarimwe: igitekerezo cya miasma, n'igitekerezo cya Edwin Klebs na Corrado Tommasi-Crudeli cy'uko malaria yaterwaga na bagiteri.

Parasite yari igaragara. Nucleus yayo ntiyagaragaraga, bituma imiterere yayo ikomeza kutamenyekana. Ernst Malachowski, umuganga wakoreraga i Breslau, yakemuye icyo kibazo kubw'impanuka hanyuma abikora abigambiriye. Mu 1889 yabonye nucleus ya plasmodium ifata irangi mu buryo butandukanye mu cyitegererezo kimwe, ariko ntiyabasha kubisubiramo. Kongera acidity ya methylene blue ntibyafashije. Kuyigira alkaline akoresheje borax byatumaga iyo ngaruka iboneka buri gihe. Yerekanye ubwo buryo mu ruhame ku wa 15 Kamena 1890 kandi abutangaza muri uwo mwaka, asohora uburyo burambuye kurushaho muri Kanama 1891.

Dmitri Romanowsky yatangaje uburyo bwe muri Nzeri 1891. Ibisubizo bye byiza cyane byaturutse mu icupa rya methylene blue ryari ryarirengagijwe, ririmo uruhumbu, kandi umuti urimo umaze amezi arenga abiri. Ibisobanuro bya Malachowski byari byateguwe nkana kandi, nk'uko yabivuze, byashoboraga gusubirwamo byoroshye; ibya Romanowsky byari inzira yapfiriye aho yakoresheje rimwe gusa. Nubwo bimeze bityo, izina ry'ubwo buryo ryitiriwe Romanowsky, kandi impaka ku muntu wakoze ibara ry'umutuku ryatumye nucleus igaragara ni indi nkuru yihariye ifite inyandiko zayo.

Ishusho: igishushanyo cya kabiri cy'ubushyuhe cyo muri raporo ya Guttmann na Ehrlich yo mu 1891. Igice cyo hejuru gikubiyemo kuva ku wa 13 kugeza ku wa 24 Nyakanga, naho icyo hasi kuva ku wa 25 Nyakanga kugeza ku wa 5 Kanama; ibyanditswe ku ruhande bigaragaza ingano zatanzwe, kandi ubushyuhe bukomeza kuba hafi y'ibisanzwe mu byumweru bitatu bya nyuma by'inyandiko. Cyakuwe muri raporo nk'uko yasikaniwe Krafts, Hempelmann na Skórska-Stania, Parasitology Research 111:1–6 (2012), PMID 22411634.

Byagaragaye ko "ripening" yari demethylation

Nta muntu n'umwe wabigizemo uruhare mu myaka ya 1890 wari uzi icyo "ripening" yakoraga kuri methylene blue. Igisubizo cyaturutse muri shimi y'inganda. Heinrich August Bernthsen yari yarakoze phenothiazine, uruvange rw'ibanze, mu buryo bwa sintetike mu 1883, agaragaza mu 1885 ko methylene blue yari muri uwo muryango, kandi muri icyo gihe kimwe yerekana ko ibihe bya alkaline bikuraho methyl groups ku irangi, bigatanga ibinyabutabire ubu byitwa azures.

Bernard Nocht yakuye igice gikora muri 1898 na 1899 kandi yashoboraga gusa kucyita Rot aus Methylenblau, umutuku ukomoka kuri methylene blue. Michaelis yacyemeje nka azure I mu 1901. Jenner yatangije ikoreshwa rya absolute methanol nk'umushongi w'uduce tw'irangi twari twabumbanye mu 1899, bikuraho igikenewe cyo gukoresha ubushyuhe mu gufatisha blood films; Leishman na Reuter bahuje ibyo byombi; Wright atangaza uburyo bworoshye mu 1902. Umusanzu wa Giemsa, na wo wo mu 1902, wari ukureka gushingira ku muti wari wararipened mu buryo butagenzuwe, ahubwo hagakoreshwa ingano zapimwe z'amabara azwi. Nyuma yanze gutangaza uko yakoraga methylene azure itanduye maze agurisha ubwo buryo kuri laboratwari ya Dr. Grübler, yagurishaga icyo gicuruzwa nka azure I kandi ikavuga ko ari yo yonyine yari irangi rya Giemsa ry'umwimerere.

Intambara ebyiri z'isi zarangije icyo gikorwa ku bw'impanuka. Igihe amabara yo mu Budage yaburaga, Lillie, Roe na Wilcox bakoze ku yasimburaga yo muri Amerika maze basanga gusiga neza cyane byaturukaga ku bice bitatu bitandukanyijwe: methylene blue itanduye, igicuruzwa cyo kwangirika kwayo azure B, na eosin. Ibyo bitatu biracyari ibice by'ingenzi by'irangi rikoreshwa mu gusuzuma malaria uyu munsi, munsi y'izina ubu rihuza Malachowski, Wright na Giemsa.

Ishusho: imiterere y'impeta ya Plasmodium falciparum mu ngirabuzimafatizo zitukura z'umuntu, yasizwe hakoreshejwe uburyo bwo mu bwoko bwa Romanowsky. Imiterere y'umutuku iri imbere mu mpeta ni chromatin uburyo bwa Malachowski bwa methylene blue yavuwe na borax bwatumye igaragara bwa mbere. Ishusho ya Ernst Hempelmann, yashyizwe mu mutungo rusange.

Izina rimwe, ibikoresho byinshi

Imyaka yatandukanyije ibyo bice yasize ikibazo cyamaze igihe kirekire kurusha shimi yabyo. Ralph Lillie yashyizeho itandukaniro mu 1969 hagati y'amabara akoreshwa mu binyabuzima, "akorwa hakurikijwe ibisabwa bikomeye bihwanye n'uko ikoreshwa ryayo ryoroshye kandi risaba ukuri", n'amabara atari ay'ibinyabuzima akoreshwa ku myenda, "asaba amahame y'inganda adakomeye kandi adasaba byinshi". Ubwoko bwombi bw'ibicuruzwa bwitwaga izina rimwe, kandi itandukaniro ryabwo ntiryigeze riba iry'urwego gusa. Ibisabwa byandikiwe ipamba n'ibisabwa byandikiwe reagent yo kwisuzumisha ntibisimburana, kandi ibikoresho byakozwe hakurikijwe ibisabwa by'imyenda ntibyagenewe kumirwa.

Azure B ni urugero rusobanutse cyane. Ni ubwoko bwa methylene blue bwakuweho methyl group imwe, bufite ibikorwa bya pharmacological bipimika ubwabwo, kandi bwari bumaze imyaka irenga ijana buba mu myiteguro ya methylene blue yo mu buvuzi nk'igice kitagenzuwe mbere y'uko hagira umuntu utandukanya byombi. Itsinda rimwe ryasanze ingirangingo z'umuntu zafashwe mu isuzuma nyuma y'urupfu nyuma yo guhabwa methylene blue zarimo 5 kugeza 14 ku ijana bya methylene blue itarahindutse na 86 kugeza 95 ku ijana bya azure B. Kumenya niba umuti runaka ugomba kuba urimo azure B, n'urugero ntarengwa igomba kugeraho, ni ikibazo cy'ibisabwa ku bwiza, kandi ubushakashatsi kuri azure B nk'umwanda n'ikinyabutabire gikomoka kuri metabolism bukomereza aho.

Ibisabwa ku bwiza ni na ho ingaruka zifatika zigaragara. Kubahiriza USP ni inzira iganisha ku rwego rwo hejuru rw'ubuziranenge ruboneka ku isoko, kuko ari igipimo cyuzuye cy'ibizamini cyatangajwe aho kuba igipimo kimwe gusa. Gikubiyemo kumenya umwirondoro, assay, imyanda ya organic harimo amabara ya azure, residual solvents, elemental impurities, residue on ignition, microbial limits, na bacterial endotoxins. Icyemezo gitanga gusa igisubizo cy'ibipimo bya heavy-metal maze kikacyita kubahiriza USP kiba gitangaje umurongo umwe gusa muri urwo rutonde.

Blupreme ibona methylene blue yayo ku ruganda rukora imiti kandi igatangaza certificate of analysis yuzuye, igasuzuma ibisabwa byose bya USP aho gupima heavy metals gusa. Ubuyobozi bwo gusoma certificate of analysis na icyo izina rya USP ryemeza n'icyo ritemeza bisobanura uburyo bwo kugenzura inyandiko ukayigereranya n'ibivugwa.

Icyo amateka yemerera kuvuga, n'icyo atemerera

Uru ruhererekane rw'amateka ni nyarwo, kandi ni rurerure kurusha uko amapaji menshi y'ibicuruzwa abigaragaza. Methylene blue yakoreshejwe mu kuvura malaria mu 1891, ivugwa nk'umuti utuza mu bantu bari bafite psychosis irimo agitation mu 1899, kandi side chain yayo inyura kuri quinacrine, chloroquine, promethazine na chlorpromazine. Inyandiko ya Ehrlich yo mu 1890 afatanyije na Arthur Leppmann yasobanuye kugabanuka k'ububabare bwa neuralgic na rheumatic, hanyuma isuzuma igitekerezo cyo kugerageza irangi mu burwayi bwo mu mutwe ariko kirangwa.

Nta na kimwe muri ibyo cyemeza ikoreshwa rigezweho. Igisubizo cya malaria cyo mu 1891 cyari gishingiye ku barwayi babiri n'igishushanyo cy'ubushyuhe. Kumara igihe kirekire hamenyerewe molekile ni impamvu yo kuyiga, si igisubizo ubwacyo. Amateka y'iki kinyabutabire nk'umuti na trials zigezweho kuri malaria bisubiza ibibazo bitandukanye n'ibyo Ehrlich yabazaga, kandi endpoints zabyo zigomba gusomwa hakurikijwe icyo zisobanura ubwazo.

Hari ikintu kimwe mu nyandiko kijyanye n'igihe cya none kurusha ibyahise. Igihe abashakashatsi bakoraga trials za methylene blue kuri malaria muri Burkina Faso mu myaka ya 2000, basanze barushanwaga kubona ibikoresho byo ku rwego rwa pharmaceutical-grade, kandi batangaza ko igiciro cy'ibikoresho fatizo cyari cyazamutse hafi inshuro ijana kimaze kugira GMP validation. Irangi ryashoboraga gusimbuzwa. Umuti ntiwashoboraga gusimbuzwa. Itandukaniro Lillie yashyizeho mu 1969 ni na ryo rikigena ibiri mu icupa uyu munsi. :::