Akụkọ ihe mere eme nke methylene blue: site n’agba ruo n’ọgwụ na nyocha

Methylene blue rutere n’ahụ onye ọrịa tupu ọ rute n’ụlọ ahịa ọgwụ.

Akụkọ Paul Guttmann na Paul Ehrlich bipụtara na 1891 banyere iji agba ahụ na malaria nwere eserese okpomọkụ abụọ. Nke abụọ malitere na 13 July ruo 5 August, e dekwara ọgwụgwọ e nyere n’akụkụ eserese ahụ kwa ụbọchị. Ihe e dere na 18 na 19 July bụ "1 × 0,05 Methylenblau". Ụbọchị ndị sochirinụ depụtara ọgwụ ise na asaa nke otu oke ahụ, ma ka ọ na-erule 22 July, e tinyekwara obere quinine n’akwụkwọ ndekọ ahụ. Ahịrị okpomọkụ ahụ, nke na-agbagharị n’etiti 37 °C na 39.5 °C n’ọkara mbụ nke eserese ahụ, kwụsịrị ịrị elu na ịda mgbe agba ahụ pụtara, wee nọrọ n’etiti ihe dịka 36 °C na 37.5 °C n’ime izu atọ ndị fọdụrụ.

Onye ọrịa ahụ bụ otu n’ime mmadụ abụọ a kọwara n’akwụkwọ ahụ dịka onye ọrụ ụlọ na onye ọrụ ụgbọ mmiri. Ngwakọta ha natara abụwo agba akwa a na-ere n’ahịa ruo afọ iri na ise, ma ndị nwoke abụọ ahụ so n’ime ndị mbụ e dekọrọ na a gwọrọ ha site n’ọgwụ e ji usoro sịntetik zuru ezu mepụta nke e mere ka ọ lekwasị anya n’otu ihe dị ndụ kpọmkwem.

Agba ahụ bịara mbụ

William Henry Perkin mepụtara agba sịntetik mbụ gara nke ọma n’ahịa na 1856. Perkin dị afọ iri na asatọ, na-arụ ọrụ n’ụlọ nyocha dị n’ụlọ ya n’oge ezumike Easter, ma na-agbalị ịmepụta quinine. Kama nke ahụ, ọ nwetara ihe fọdụrụ ojii, gbazee ya, wee chọpụta agba na-arapara nke ọma n’akwa silk. O nwetara patent ya na August 1856, ma ka ọ na-erule ngwụcha 1857, o nwere ụlọ ọrụ na-ebunye agba n’ụlọ ọrụ ịgba silk dị na London.

Na 1875 Adolf von Baeyer mepụtara agba uhie ma kpọọ ya eosin, site na Eos, okwu Greek pụtara chi ọbụbọ. Na 1876 Heinrich Caro, onye bụ mgbe ahụ onye isi ụlọ nyocha na Badische Anilin- und Soda-Fabrik, mepụtara methylene blue ya na Baeyer dịka agba sitere na aniline maka owu. A naghị akwado nhazi kemịkal ya nke ọma ruo ihe dịka afọ itoolu ka e mesịrị.

A ka na-ahụ mmalite ahụ n’ụzọ e si akpọ ihe ahụ aha. "Methylene blue" bụ aha azụmahịa sitere na katalọgụ agba, ọ bụghị nkọwa kemịkal. Ngwakọta aha ahụ na-ezo aka na ya bụ methylthioninium chloride, na ọdịiche dị n’etiti aha ahụ, nnu ahụ, na hydrates ya na-amalite ịdị mkpa ozugbo mmadụ chọrọ ịtụ ihe ahụ n’arọ ma ọ bụ ịgụ nkọwapụta ya.

Ịgba ntụpọ bụ ụzọ njikọ

Ụzọ si n’ụlọ ọrụ agba gaa n’ụlọ ọgwụ gafere n’okpuru microscope, ma ọ malitere tupu methylene blue adị. Wilhelm Erb bụ onye mbụ tinyere agba sịntetik n’ọbara, jiri picric acid na 1865, ma hụ usoro yiri ụgbụ n’ime ụfọdụ mkpụrụ ndụ ọbara uhie.

Akwụkwọ doctoral thesis Paul Ehrlich nke 1878 tụnyere ịgba ntụpọ histological na ịgba akwa, ma kwuo na ha abụọ bụ mmeghachi omume kemịkal. Mgbe ọ na-arụ ọrụ n’okpuru Robert Koch banyere tubercle bacillus, ọ kewara aniline dyes n’ìgwè acid na basic ma gosipụta na ìgwè ọ bụla na-agba akụkụ dị iche iche nke mkpụrụ ndụ agba. Na 1880 ọ gwakọtara ha abụọ: ọ wụsara saturated solution nke methylene blue n’ime acid fuchsin ruo mgbe mmiri dị n’elu ngwakọta ahụ doro anya. Ihe si na ya pụta, nke ọ kpọrọ neutralen Farbkörper ma ọ bụ neutral stain, mepụtara agba atọ kama otu, kpughee granules n’ime polymorphonuclear cells ndị a na-ahụbeghị mbụ, ma mee ka o kwe omume ime leukocyte differential count mbụ. N’ihi na granules ndị ahụ nabatara akụkụ abụọ nke ngwakọta ahụ, Ehrlich mepụtara okwu neutrophil maka mkpụrụ ndụ ndị bu ha.

Afọ abụọ ka e mesịrị Koch jiri methylene blue chọta tubercle bacillus, ma na 1883 Ehrlich meziwanye usoro ahụ. Na 1886 ọ bipụtara ụdị nlele ọzọ: o tinyere agba ahụ n’ahụ anụmanụ dị ndụ site n’injection ma tụnyere otú akụkụ ahụ dị iche iche si nabata ya nke ukwuu, wee kwubie na ọ nwere mmasị pụtara ìhè n’anụ ahụ ụbụrụ na akwara. O jikọtara mmasị ahụ na oxidation-reduction cycling nke agba ahụ, nke o hụrụ n’afọ gara aga. Cycling ahụ bụkwa ihe kpatara solution methylene blue ji tufuo agba ya mgbe oxygen dị n’ime ya gwụsịrị ma nwetaghachi ya mgbe ikuku laghachiri. Nnwale ndị mbụ tụrụ ihe si na cycling ahụ pụta bụ nke afọ iri ọzọ, ma usoro ahụ n’onwe ya bụ isiokwu dị iche na akụkọ ihe mere eme.

Parasite ahụ na nucleus odo-uhie

Alphonse Laveran chọpụtara parasite malaria na 1880 site n’inyocha ọbara ọhụrụ a na-agbabeghị ntụpọ. Iji hụ ya mgbe niile n’ime smear akọrọ chọrọ stain, ma stains nke oge ahụ na-emepụta naanị uhie na anụnụ anụnụ.

Na 1888 onye Polish pathologist Czesław Cheçinski jiri eosin dochie acid fuchsin, wee mepụta ngwakọta methylene blue na eosin. Ihe mere o ji mepụta usoro ahụ sitere n’aka otu onye agha nwụrụ n’ihi malaria na 30 September 1887. N’ime blood films, Cheçinski hụrụ ụdị anụnụ anụnụ yiri okooko daisy, nke a na-amata ugbu a dịka Plasmodium malariae, yana ụdị yiri mma owuwe ihe ubi, nke a na-amata ugbu a dịka gametocytes nke Plasmodium falciparum. Nsonaazụ ahụ kwụsịrị nkọwa abụọ na-asọrịta mpi banyere ọrịa ahụ n’otu oge: echiche miasma, na nkwupụta Edwin Klebs na Corrado Tommasi-Crudeli na nje bacterium na-akpata malaria.

A pụrụ ịhụ parasite ahụ. Ma a pụghị ịhụ nucleus ya, nke mere ka ụdị ihe ọ bụ ka bụrụ ajụjụ mepere emepe. Ernst Malachowski, dibịa nọ na Breslau, doziri nsogbu ahụ n’amaghị ama ma mesịa mee ya n’amamihe. Ọ hụrụ differential staining nke plasmodial nucleus n’otu preparation na 1889 ma o nweghị ike imegharị nsonaazụ ahụ. Ime methylene blue ka ọ bụrụ acidic enyereghị aka. Ịgbakwunye borax iji mee ya alkaline na-emepụta mmetụta ahụ oge ọ bụla. O gosipụtara usoro ahụ n’ihu ọha na 15 June 1890 ma bipụta ya n’otu afọ ahụ, yana usoro zuru ezu karị na August 1891.

Dmitri Romanowsky bipụtara ụdị nke ya na September 1891. Nsonaazụ ya kacha mma sitere na karama solution methylene blue ochie, nke e leghaara anya ma jupụta mould, nke dị ihe karịrị ọnwa abụọ. Akụkọ Malachowski bụ nke e mere n’amụma ma, n’okwu ya, dị mfe ịmegharị; nke Romanowsky bụ ụzọ kwụsịrị n’ebe ahụ nke rụrụ ọrụ otu ugboro. N’agbanyeghị nke ahụ, aha eponym ahụ gara Romanowsky, ma esemokwu banyere onye mepụtara agba odo-uhie nke mere ka nucleus pụta ìhè bụ akụkọ dị iche nwere akwụkwọ nke ya.

Onyonyo: eserese okpomọkụ nke abụọ sitere n’akụkọ Guttmann na Ehrlich nke 1891. Akụkụ elu na-ekpuchi 13 ruo 24 July, akụkụ ala na-ekpuchi 25 July ruo 5 August; ihe e dere n’akụkụ na-akpọ dose ndị e nyere aha, ma okpomọkụ ahụ na-anọ nso na nke nkịtị n’ime izu atọ ikpeazụ nke ndekọ ahụ. E megharịrị ya site n’akụkọ ahụ dịka e si scan ya maka Krafts, Hempelmann na Skórska-Stania, Parasitology Research 111:1–6 (2012), PMID 22411634.

“Ripening” mechara bụrụ demethylation

Ọ dịghị onye sonyere n’ọrụ ndị ahụ n’afọ 1890s maara ihe "ripening" na-eme methylene blue. Azịza ya sitere na kemịkal ụlọ ọrụ. Heinrich August Bernthsen mepụtara parent compound phenothiazine na 1883, gosipụta na 1885 na methylene blue so n’ezinụlọ ahụ, ma gosikwa n’otu oge ahụ na ọnọdụ alkaline na-ewepụ methyl groups n’agba ahụ, na-emepụta ngwakọta ndị a na-akpọ azures ugbu a.

Bernard Nocht wepụtara active fraction ahụ na 1898 na 1899 ma nwee ike ịkpọ ya naanị Rot aus Methylenblau, uhie sitere na methylene blue. Michaelis kọwara ya dịka azure I na 1901. Jenner webatara absolute methanol dịka solvent maka precipitate agba ahụ na 1899, nke wepụrụ mkpa nke iji okpomọkụ fix blood films; Leishman na Reuter jikọtara ọganihu abụọ ahụ; Wright bipụtara usoro dị mfe na 1902. Ihe Giemsa gbakwunyere, kwa na 1902, bụ ịkwụsị ịdabere na solution “ripened” n’enweghị njikwa ma jiri oke dyes a maara nke a tụrụ kpọmkwem kama ya. Mgbe ahụ, ọ jụrụ ibipụta otu o si emepụta pure methylene azure ma ree usoro ahụ nye ụlọ nyocha Dr. Grübler, nke rere ngwaahịa ahụ dịka azure I ma kwuo na naanị ụdị nke ya bụ ezigbo Giemsa stain.

Agha ụwa abụọ mechara rụchaa ọrụ ahụ n’amaghị ama. Mgbe dyes Germany ghọrọ ihe a na-apụghị inweta, Lillie, Roe na Wilcox rụrụ ọrụ na ihe ndị America ji dochie ha ma chọpụta na staining kacha mma sitere n’akụkụ atọ e kewapụrụ: pure methylene blue, ihe mmebi ya azure B, na eosin. Ihe atọ ahụ ka bụ isi ihe mejupụtara stain a na-eji achọpụta malaria taa, n’okpuru aha nke na-ejikọta Malachowski, Wright na Giemsa ugbu a.

Onyonyo: ụdị mgbanaka Plasmodium falciparum n’ime mkpụrụ ndụ ọbara uhie mmadụ, nke e ji usoro ụdị Romanowsky stain. Nhazi odo-uhie dị n’ime mgbanaka ahụ bụ chromatin nke methylene blue Malachowski gwọrọ na borax mere ka a hụ ya nke mbụ. Ernst Hempelmann kere onyonyo ahụ ma hapụ ya n’ime public domain.

Otu aha, ihe dị iche iche

Afọ ndị kewapụrụ ihe ndị ahụ hapụrụ nsogbu nke dịgidere karịa kemịkal ahụ. Ralph Lillie kewapụtara biological stains na 1969, "nke a na-emepụta dịka nkọwapụta siri ike dabara n’iji ha eme ihe nke chọrọ nlezianya na izi ezi", na non-biological stains maka ịgba akwa, nke "na-achọ ụkpụrụ nrụpụta na-adịchaghị ike ma na-adịchaghị achọ ihe". Ụdị ngwaahịa abụọ ahụ nwere otu aha, ma ọdịiche dị n’etiti ha abụghị naanị ọdịiche n’ogo. Nkọwapụta e dere maka owu na nkọwapụta e dere maka diagnostic reagent enweghị ike dochie ibe ha, ma ihe e mere dịka nkọwapụta akwa ahụ si dị abụghị nke e mere ka mmadụ rie.

Azure B bụ ihe atụ kacha doo anya. Ọ bụ ụdị monodemethylated nke methylene blue, ọ nwere pharmacological activity nke a pụrụ ịtụ n’onwe ya, ma ọ nọ dịka constituent a na-achịkwaghị achịkwa n’ime clinical methylene blue preparations ruo ihe karịrị otu narị afọ tupu onye ọ bụla ekewapụ ha abụọ. Otu ìgwè chọpụtara na anụ ahụ mmadụ e wepụtara n’oge autopsy mgbe e nyesịrị methylene blue nwere 5 ruo 14 per cent methylene blue na-agbanwebeghị na 86 ruo 95 per cent azure B. Ma preparation e nyere kwesịrị ịnwe azure B, yana oke kwesịrị ịbụ ole, bụ ajụjụ nkọwapụta, ma nyocha banyere azure B dịka impurity na metabolite na-amalite site n’ebe ahụ.

Nkọwapụta bụkwa ebe nsonaazụ bara uru dị. Ịgbaso USP bụ ụzọ e si ruo n’ogo ịdị ọcha kachasị elu ahịa na-enye, n’ihi na ọ bụ ụkpụrụ ule zuru ezu e bipụtara, ọ bụghị otu measurement. Ọ na-ekpuchi identity, assay, organic impurities gụnyere azure dyes, residual solvents, elemental impurities, residue on ignition, microbial limits, na bacterial endotoxins. Certificate nke na-akọ heavy-metal result ma kpọọ ya USP compliance akọpụtala naanị otu ahịrị n’ime ndepụta ahụ.

Blupreme na-enweta methylene blue ya n’aka onye nrụpụta ọgwụ ma na-ebipụta certificate of analysis zuru ezu, na-anwale nkọwapụta USP dum kama heavy metals naanị. Nduzi maka ịgụ certificate of analysis na ihe akara USP na-egosi na ihe ọ na-adịghị egosi na-akọwa otu esi elele akwụkwọ ahụ megide nkwupụta ahụ.

Ihe akụkọ ihe mere eme na-enye nkwado ikwu, na ihe ọ na-enyeghị

Usoro akụkọ ahụ bụ eziokwu, ma ọ dị ogologo karịa ka ọtụtụ product pages na-egosi. E jiri methylene blue gwọọ malaria na 1891, a kọọrọ ya dịka sedative n’ọnọdụ agitated psychosis na 1899, ma side chain ya gafere quinacrine, chloroquine, promethazine na chlorpromazine. Akwụkwọ Ehrlich nke 1890 ya na Arthur Leppmann kọwara mbelata neuralgic na rheumatic pain, ma mesịa tụlee iji agba ahụ na mental illness ma kpebie ịghara ịnwale ya.

Ọ dịghị nke ọ bụla n’ime ihe ndị ahụ na-egosi ojiji nke oge a. Nsonaazụ malaria nke 1891 bụ ndị ọrịa abụọ na eserese okpomọkụ. Ịma molecule ogologo oge bụ ihe mere e ji kwesị ịmụ ya, ọ bụghị nsonaazụ. Akụkọ ihe mere eme nke ngwakọta ahụ dịka ọgwụ na nnwale oge a banyere malaria na-aza ajụjụ dị iche na nke Ehrlich na-ajụ, ma a ga-agụ endpoints ndị ahụ dịka ihe ha n’onwe ha pụtara.

E nwere otu nkọwa n’ime ndekọ ahụ nke bụ nke oge ugbu a karịa nke gara aga. Mgbe ndị nyocha mere nnwale methylene blue maka malaria na Burkina Faso n’afọ 2000s, ha hụrụ onwe ha ka ha na-asọmpi maka pharmaceutical-grade material, ma kọọ na ọnụ ahịa raw material arịgoro ihe dịka ugboro otu narị ozugbo o nwetara GMP validation. A pụrụ iji agba dochie ihe ọzọ. A pụghị ime otu ihe ahụ n’ọgwụ. Ọdịiche Lillie kọwara na 1969 bụ otu ọdịiche ahụ na-ekpebi ihe dị n’ime karama taa. :::