Meiyuan Qian, Yuefeng Tan, Bo Xu
Porogaramu R&D Ikigo
Intangiriro
Tagisi (Taxus chinensis cyangwa yew yo mu Bushinwa) ni igihingwa cyo mu gasozi kirinzwe nigihugu.Ni igihingwa kidasanzwe kandi kigeramiwe cyasizwe inyuma na glaciers ya Quaternary.Nicyo kimera cyonyine kivura imiti kwisi.Tagisi ikwirakwizwa mu karere gashyuha gaherereye mu majyaruguru y’akarere ka ruguru rwagati, hamwe n’amoko agera kuri 11 ku isi.Mu Bushinwa hari amoko 4 n'ubwoko 1, aribwo Tagisi y'Amajyaruguru y'Uburasirazuba, Tagisi Yunnan, Tagisi, Tagisi ya Tibet na Tagisi y'Amajyepfo.Ubu bwoko butanu bukwirakwizwa mu majyepfo y’iburengerazuba bw’Ubushinwa, Ubushinwa bw’Amajyepfo, Ubushinwa bwo hagati, Ubushinwa bw’Uburasirazuba, Uburengerazuba bw’Ubushinwa, Amajyaruguru y’Ubushinwa na Tayiwani.Ibimera bya tagisi birimo ibintu byinshi bigize imiti, harimo tagisi, flavonoide, lignans, steroid, acide fenolike, sesquiterpène na glycoside.Umuti uzwi cyane wo kurwanya ibibyimba Taxol (cyangwa Paclitaxel) ni ubwoko bwa tagisi.Taxol ifite uburyo bwihariye bwo kurwanya antikanseri.Taxol irashobora "gukonjesha" microtubules mukuyihuza nayo kandi ikabuza microtubules gutandukanya chromosomes mugihe cyo kugabana selile, bityo bikaviramo urupfu rwingirabuzimafatizo, cyane cyane kanseri ya kanseri ikwirakwira vuba [1].Byongeye kandi, mugukora macrophage, Taxol itera kugabanuka kwakirwa rya TNF-α (tumor necrosis factor) no kurekura TNF-α, bityo bikica cyangwa bikabuza ingirabuzimafatizo [2].Byongeye kandi, Taxol irashobora gutera apoptose ikoresheje inzira ya reseptor ya apoptotique yunganirwa na Fas / FasL cyangwa igakora sisitemu ya protease ya sisitemu [3].Bitewe n'ingaruka nyinshi zirwanya anticancer, Taxol ikoreshwa cyane mukuvura kanseri yintanga, kanseri yamabere, kanseri yibihaha ntoya (NSCLC), kanseri yo mu gifu, kanseri yo mu nda, kanseri y'uruhago, kanseri ya prostate, melanoma mbi, umutwe n'ijosi kanseri, n'ibindi [4].By'umwihariko kuri kanseri y'ibere yateye imbere na kanseri y’intanga ngore, Taxol igira ingaruka zidasanzwe zo kuvura, bityo izwi nka "umurongo wa nyuma wo kwirinda kanseri".
Taxol niwo muti uzwi cyane ku isoko mpuzamahanga mu myaka yashize kandi ufatwa nk'imwe mu miti igabanya ubukana bwa muntu mu myaka 20 iri imbere.Mu myaka yashize, hamwe n’ubwiyongere bukabije bw’abaturage n’abafite kanseri, icyifuzo cya Taxol nacyo cyiyongereye ku buryo bugaragara.Kugeza ubu, Taxol isabwa mubushakashatsi bwubuvuzi cyangwa siyanse ikurwa cyane muri Taxus.Kubwamahirwe, ibikubiye muri Taxol mubihingwa ni bike.Kurugero, ibirimo bya Taxol ni 0.069% gusa mubishishwa bya Taxus brevifolia, mubisanzwe bifatwa nkibiri hejuru.Gukuramo 1 g ya Taxol, bisaba hafi kg 13,6 ya tagisi.Ukurikije iki kigereranyo, bisaba ibiti bya Tagisi 3 - 12 bimaze imyaka irenga 100 kuvura umurwayi wa kanseri yintanga.Kubera iyo mpamvu, umubare munini wibiti bya Tagisi byaraciwe, bituma hafi yubwoko bubi.Byongeye kandi, Tagisi irakennye cyane mubutunzi kandi itinda gukura, ibyo bigatuma bigora iterambere no gukoresha Taxol.
Kugeza ubu, synthesis yose ya Taxol yarangiye neza.Nyamara, inzira yubukorikori iragoye cyane kandi ihenze cyane, bigatuma idafite akamaro munganda.Uburyo bwa kimwe cya kabiri cya Taxol burakuze kandi bifatwa nkuburyo bwiza bwo kwagura isoko ya Taxol hiyongereyeho gutera ibihingwa.Muri make, muri kimwe cya kabiri cya synthesis ya Taxol, uruganda rwa Taxol precursor rwinshi cyane mu bimera bya Taxus rurakurwa hanyuma ruhindurwa muri Taxol hakoreshejwe synthesis.Ibiri muri 10-deacetylbaccatin Ⅲ mu nshinge za Taxus baccata birashobora kugera kuri 0.1%.Kandi inshinge ziroroshye kubyara ugereranije nibishishwa.Kubwibyo, igice cya synthesis ya Taxol ishingiye kuri 10-deacetylbaccatin Ⅲ ikurura abashakashatsi benshi [5] (nkuko bigaragara ku gishushanyo 1).
Igicapo 1. Inzira ya sintetike yinzira ya Taxol ishingiye kuri 10-deacetylbaccatin Ⅲ.
Muri iyi nyandiko, ibimera biva mu ruganda rwa Taxus byahanaguwe na sisitemu ya flash itegura amazi ya chromatografiya ya SepaBean ™ ifatanije na SepaFlash C18 ihinduranya icyiciro (RP) flash cartridges yakozwe na Santai Technologies.Igicuruzwa cyibanze cyujuje ibyangombwa bisukuye cyabonetse kandi gishobora gukoreshwa mubushakashatsi bwakurikiyeho, gitanga igisubizo cyigiciro cyogusukura byihuse ubwoko bwibicuruzwa bisanzwe.
Igikoresho | SepaBean ™ imashini | |
Cartridge | 12 g SepaFlash C18 RP flash cartridge (silika spherical, 20 - 45μm, 100 Å, nimero ya ordre : SW-5222-012-SP) | |
Uburebure | 254 nm (gutahura), 280 nm (gukurikirana) | |
Icyiciro cya mobile | Umuti A: Amazi | |
Umuti B: Methanol | ||
Igipimo cyo gutemba | 15 mL / min | |
Icyitegererezo | 20 mg icyitegererezo kibisi cyashonga muri 1 mL DMSO | |
Gradient | Igihe (min) | Umuti B (%) |
0 | 10 | |
5 | 10 | |
7 | 28 | |
14 | 28 | |
16 | 40 | |
20 | 60 | |
27 | 60 | |
30 | 72 | |
40 | 72 | |
43 | 100 | |
45 | 100 |
Ibisubizo n'ibiganiro
Amashanyarazi ya chromatogramu yavuye muri Taxus yerekanwe ku gishushanyo cya 2. Mu gusesengura chromatogramu, ibicuruzwa bigenewe hamwe n’umwanda byageze ku gutandukanya ibice.Byongeye kandi, imyororokere myiza nayo yatahuwe ninshinge nyinshi zintangarugero (data aterekanwa).Bizatwara amasaha agera kuri 4 kugirango urangize gutandukana muburyo bwa chromatografiya nuburyo bwikirahure.Ugereranije nuburyo gakondo bwa chromatografiya, uburyo bwo kweza bwikora muriyi nyandiko bisaba iminota 44 gusa kugirango urangize umurimo wose wo kweza (nkuko bigaragara ku gishushanyo 3).Kurenga 80% yigihe kinini kandi kinini gishobora gukizwa ukoresheje uburyo bwikora, bushobora kugabanya neza ikiguzi kimwe no kuzamura imikorere neza.
Igicapo 2. Flash chromatogramu yikuramo ryibicuruzwa biva muri Tagisi.
Igicapo 3. Kugereranya uburyo bwa chromatografiya nuburyo bwo kweza byikora.
Mu gusoza, guhuza SepaFlash C18 RP flash cartridges hamwe na mashini ya SepaBean ™ birashobora gutanga igisubizo cyihuse kandi cyiza cyo kweza byihuse ibicuruzwa bisanzwe nkibikomoka kuri Taxus.
Reba
1. Alushin GM, Lander GC, Kellogg EH, Zhang R, Baker D na Nogales E. Imiterere ya microtubule ihanitse cyane yerekana inzibacyuho yimiterere muri αβ-tubuline kuri hydrolysis ya GTP.Akagari, 2014, 157 (5), 1117-1129.
2. Burkhart CA, Berman JW, Swindell CS na Horwitz SB.Isano iri hagati yimiterere ya Tagisi nandi matagisi yo kwinjiza Tumor Necrosis Factor-α Imvugo ya Gene na Cytotoxicity.Ubushakashatsi bwa Kanseri, 1994, 54 (22), 5779-5782.
3. Parike SJ, Wu CH, Gordon JD, Zhong X, Emami A na Safa AR.Tagisi itera Caspase-10-iterwa na Apoptose, J. Biol.Chem., 2004, 279, 51057-51067.
4. Paclitaxel.Sosiyete y'Abanyamerika yubuzima-Sisitemu ya Farumasi.[Ku ya 2 Mutarama 2015]
5. Bruce Ganem na Roland R. Franke.Paclitaxel kuva muri Tagisi Yibanze: Icyerekezo cyo guhanga ibintu bishya muri chimie ya Organozirconium.J. Org.Chem., 2007, 72 (11), 3981-3987.
Hano hari urukurikirane rwa flash ya SepaFlash C18 RP hamwe nibisobanuro bitandukanye bivuye muri tekinoroji ya Santai (nkuko bigaragara mu mbonerahamwe ya 2).
Umubare w'ingingo | Ingano yinkingi | Igipimo cy'Uruzi (mL / min) | Icyiciro (psi / bar) |
SW-5222-004-SP | 5.4 g | 5-15 | 400 / 27.5 |
SW-5222-012-SP | 20 g | 10-25 | 400 / 27.5 |
SW-5222-025-SP | 33 g | 10-25 | 400 / 27.5 |
SW-5222-040-SP | 48 g | 15-30 | 400 / 27.5 |
SW-5222-080-SP | 105 g | 25-50 | 350 / 24.0 |
SW-5222-120-SP | 155 g | 30-60 | 300 / 20.7 |
SW-5222-220-SP | 300 g | 40-80 | 300 / 20.7 |
SW-5222-330-SP | 420 g | 40-80 | 250 / 17.2 |
Imbonerahamwe 2. SepaFlash C18 RP flash cartridges.
Ibikoresho byo gupakira: Ubukorikori buhanitse bwa C18 buhujwe na silika, 20 - 45 mm, 100 Å
Kubindi bisobanuro birambuye kubisobanuro birambuye bya mashini ya SepaBean ™, cyangwa amakuru yo gutumiza kumurongo wa flash cartridges ya SepaFlash, nyamuneka sura urubuga
Igihe cyo kohereza: Nzeri-20-2018