Meiyuan Qian, Yuefeng Tan, Bo Xu
Talosaga R&D Nofoaga Autu
Folasaga
Taxus (Taxus chinensis po'o le Chinese yew) o se laau vao e puipuia e le atunuu.Ose la'au e seasea ma fa'aleagaina na tu'ua e le Quaternary glaciers.E na'o le pau lea o le vaila'au fa'alenatura i le lalolagi.Taxus o loʻo tufatufa atu i le sone malulu o le itu i matu o le itulagi i le ogatotonu o le itulagi, ma e tusa ma le 11 ituaiga i le lalolagi.E 4 ituaiga ma 1 ituaiga i Saina, e pei o Northeast Taxus, Yunnan Taxus, Taxus, Tibetan Taxus ma Southern Taxus.O nei ituaiga e lima o loʻo tufatufaina i Southwest China, South China, Central China, East China, Northwest China, Northeast China ma Taiwan.La'au lafoga o lo'o i ai le tele o vaega vaila'au, e aofia ai taxanes, flavonoids, lignans, steroids, phenolic acids, sesquiterpenes ma glycosides.Ole vaila'au ta'uta'ua ole tumor Taxol (po'o Paclitaxel) o se ituaiga o lafoga.Taxol ei ai faiga fa'apitoa e fa'ama'i ai le kanesa.Taxol e mafai ona "fa'aisa" microtubules e ala i le selu faatasi ma latou ma puipuia microtubules mai le vavaeeseina o chromosomes i le taimi o le vaevaega o sela, ma mafua ai le oti o sela vaeluaina, aemaise lava le vave faʻateleina o sela o le kanesa [1].E le gata i lea, e ala i le faʻagaoioia o macrophages, Taxol e mafua ai le faʻaitiitia o le TNF-α (tumor necrosis factor) faʻafeiloaʻi ma le faʻasaʻoina o le TNF-α, ma faʻaumatia pe taofia ai sela tumo [2].E le gata i lea, e mafai e Taxol ona faʻaosofia le apoptosis e ala i le galue i luga o le auala faʻafeiloaʻi apoptotic faʻasalalau e Fas / FasL poʻo le faʻagaoioia o le cysteine protease system [3].Ona o le tele o le aʻafiaga o le anticancer, Taxol e masani ona faʻaaogaina i le togafitiga o le kanesa ovarian, kanesa o le susu, kanesa mama mama (NSCLC), kanesa o le manava, kanesa o le esophageal, kanesa o le manava, kanesa prostate, melanoma leaga, ulu ma ua. kanesa, ma isi[4].Aemaise lava mo le kanesa o le susu maualuga ma le kanesa ovarian maualuga, Taxol ei ai lona aafiaga mataʻina fofo, o lea ua lauiloa ai o le "laina mulimuli o le puipuiga mo togafitiga o le kanesa".
Taxol o le vailaʻau faʻamaʻi sili ona lauiloa i maketi faavaomalo i tausaga talu ai ma ua manatu o se tasi o vailaʻau faʻamaʻi sili ona aoga mo tagata i le isi 20 tausaga.I tausaga talu ai nei, faʻatasi ai ma le faʻatupulaia o le faitau aofaʻi ma le kanesa, o le manaʻoga mo Taxol ua faʻateleina foi.Ole taimi nei, ole Taxol e mana'omia mo su'esu'ega fa'afoma'i po'o su'esu'ega fa'asaienisi e masani lava ona aumai sa'o mai Taxus.Ae paga lea, o mea o loʻo i totonu o Taxol i laʻau e fai si maualalo.Mo se faʻataʻitaʻiga, o le Taxol content e naʻo le 0.069% i le paʻu o Taxus brevifolia, lea e masani ona manatu e sili ona maualuga mea.Mo le mauaina o le 1 g o Taxol, e manaʻomia le tusa ma le 13.6 kilokalama o le paʻu o Taxus.E tusa ai ma lea fa'atatau, e mana'omia le 3 - 12 Taxus la'au ua silia ma le 100 tausaga le matutua e togafitia ai se gasegase o le kanesa ovarian.O le i'uga, o le tele o la'au Taxus ua ta'oto i lalo, ma i'u ai ina toeitiiti mou atu lea ituaiga o meaola.E le gata i lea, o Taxus e matua mativa lava i punaoa ma telegese le tuputupu ae, lea e faigata ai mo le faʻalauteleina ma le faʻaaogaina o Taxol.
I le taimi nei, ua maeʻa lelei le faʻasologa o Taxol.Ae ui i lea, o lona auala faʻapipiʻi e matua faigata tele ma maualuga le tau, ma e leai se taua o pisinisi.Ole auala semi-synthetic ole Taxol ua matua'i matua ma ua manatu ose auala aoga e fa'alautele ai le puna ole Taxol fa'aopoopo ile totō fa'afua.I se faapuupuuga, i le semi-synthesis o Taxol, o le Taxol precursor compound lea e fai si tele i laau o le Taxus ua maua mai ona liua lea i Taxol e ala ile chemical synthesis.Ole mea ole 10-deacetylbaccatin Ⅲ ile nila ole Taxus baccata e mafai ona oʻo ile 0.1%.Ma o nila e faigofie ona toe faʻafouina pe a faʻatusatusa i paʻu.O le mea lea, o le semi-synthesis o Taxol e faʻavae i luga o le 10-deacetylbaccatin Ⅲ o loʻo tosina mai ai le tele ma sili atu le gauai mai tagata suʻesuʻe [5] (e pei ona faʻaalia i le Ata 1).
Ata 1. Ole auala semi-synthetic ole Taxol e fa'avae ile 10-deacetylbaccatin Ⅲ.
I lenei pou, o le Taxus plant extract na fa'amamāina e se masini fa'apipi'i fa'apipi'i fa'ama'i vai SepaBean™ fa'atasi ma SepaFlash C18 reversed-phase (RP) flash cartridges na gaosia e Santai Technologies.O le oloa faʻatatau e fetaui ma manaʻoga mama na maua ma e mafai ona faʻaaogaina i suʻesuʻega faʻasaienisi mulimuli ane, ofoina atu se fofo taugofie mo le faʻamamaina vave o lenei ituaiga o mea faʻanatura.
Meafaigaluega | SepaBean™ masini | |
Kesi | 12 g SepaFlash C18 RP kesi moli (silika lapotopoto, 20 - 45μm, 100 Å, Numera oka:SW-5222-012-SP) | |
Umi ole galu | 254 nm (su'esu'eina), 280 nm (mata'ituina) | |
Vaega feavea'i | Solvent A: Vai | |
Solvent B: Methanol | ||
Fuafuaga tafe | 15 mL/min | |
Fa'ata'ita'iga uta | 20 mg fa'ata'ita'iga mata'utia fa'amavae ile 1 mL DMSO | |
Gradient | Taimi (min) | Solvent B (%) |
0 | 10 | |
5 | 10 | |
7 | 28 | |
14 | 28 | |
16 | 40 | |
20 | 60 | |
27 | 60 | |
30 | 72 | |
40 | 72 | |
43 | 100 | |
45 | 100 |
I'uga ma Talanoaga
O le chromatogram flash mo le fa'asoa mai le Taxus na fa'aalia i le Ata 2. I le su'esu'eina o le chromatogram, o le oloa fa'atatau ma le fa'aleagaina na ausia ai le vavae'esega fa'avae.E le gata i lea, o le toe gaosia lelei na maua foi i le tele o tui faʻataʻitaʻiga (faʻamatalaga e le o faʻaalia).E tusa ma le 4 itula e fa'amae'a ai le tu'uese'esega ile metotia chromatography tusi lesona ma koluma tioata.Fa'atusatusa i le auala masani o le chromatography tusi lesona, o le auala fa'amama fa'amama i lenei pou e mana'omia na'o le 44 minute e fa'amae'a ai le galuega fa'amamāina atoa (e pei ona fa'aalia i le Ata 3).E sili atu i le 80% o le taimi ma le tele o le solvent e mafai ona faʻaolaina e ala i le faʻaaogaina o auala faʻapitoa, lea e mafai ona faʻaitiitia lelei ai le tau faʻapea foʻi ma le faʻaleleia atili o le galuega.
Ata 2. O le chromatogram moli ole si'osi'omaga mai Taxus.
Ata 3. O le fa'atusatusaga o le chromatography fa'ata'ita'iga fa'atasi ma le fa'amama fa'aautomatika.
I le fa'ai'uga, o le fa'apipi'iina o kalama uila SepaFlash C18 RP ma le masini SepaBean™ e mafai ona ofoina atu se fofo vave ma lelei mo le fa'amama vave o mea fa'anatura e pei o le Taxus extract.
Fa'asinomaga
1. Alushin GM, Lander GC, Kellogg EH, Zhang R, Baker D ma Nogales E. Faʻatonuga maualuga microtubule faʻaaliga faʻaalia suiga faʻavae i le αβ-tubulin i luga ole GTP hydrolysis.Cell, 2014, 157 (5), 1117-1129.
2. Burkhart CA, Berman JW, Swindell CS ma Horwitz SB.Soʻotaga i le va o le Faʻatulagaina o Taxol ma Isi Taxanes i luga ole Induction of Tumor Necrosis Factor-α Gene Expression ma Cytotoxicity.Suesuega Kanesa, 1994, 54 (22), 5779-5782.
3. Park SJ, Wu CH, Gordon JD, Zhong X, Emami A ma Safa AR.Taxol Induces Caspase-10-faalagolago Apoptosis, J. Biol.Chem., 2004, 279, 51057-51067.
4. Paclitaxel.Le American Society of Health-System Pharmacists.[Ianuari 2, 2015]
5. Bruce Ganem ma Roland R. Franke.Paclitaxel mai le Primary Taxanes: O se Va'aiga i le Foafoaga Foafoa i le Organozirconium Chemistry.J. Org.Chem., 2007, 72 (11), 3981-3987.
O loʻo i ai se faʻasologa o le SepaFlash C18 RP flash cartridges ma faʻamatalaga eseese mai le Santai Technology (e pei ona faʻaalia i le Laulau 2).
Numera o mea | Tele o le koluma | Fua Faatatau (mL/min) | Max.Omiga (psi/pa) |
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 |
Fuafuaga 2. SepaFlash C18 RP kasini moli.
Mea fa'apipi'i: Silika fa'apipi'i C18 siliga lelei, 20 - 45 μm, 100 Å
Mo nisi faʻamatalaga e uiga i faʻamatalaga auiliili o le SepaBean ™ masini, poʻo le faʻatonuga o faʻamatalaga i le SepaFlash series flash cartridges, faʻamolemole asiasi i la matou upega tafaʻilagi
Taimi meli: Sep-20-2018