I-Meiyuan Qian, Yuefeng Tan, Bo Xu
Isikhungo se-R & D Center
Ukuqalisa
Amatekisi (amatekisi i-Chinensis noma i-Chinese yew) isitshalo sasendle esivikelwe izwe. Isitshalo esingajwayelekile futhi esisengozini esishiywe yiqhwa le-quaternary. Futhi kungukuphela kwesitshalo sokwelapha semvelo emhlabeni. I-TAXUS isatshalaliswa endaweni eshisayo yeNyakatho ye-Hemisphere eya esifundeni esisendaweni esemhlabeni, ngezinhlobo eziyi-11 emhlabeni. Kunezinhlobo ezi-4 nezinhlobonhlobo ezi-1 eChina, okunguNoutheast Tables, i-Yunnan tables, amatekisi, iTibetan tables kanye nentela yaseningizimu. Lezi zinhlobo ezinhlanu zisatshalaliswa eSouthwest China, eSouth China, eCentral China, e-East China, enyakatho-ntshonalanga China, eTaiwan. Izitshalo zeTaxs ziqukethe izinhlobo eziningi zamakhemikhali, kufaka phakathi ama-taxi, ama-flavonoid, ama-steroid, ama-steroid, ama-phenolic acid, ama-sesquindene kanye nama-glycosides. I-taxol yezidakamizwa edumile edumile (noma i-paclitaxel) uhlobo lwamatekisi. I-TAXELL inezindlela ezihlukile ze-anticancer. I-TaXOLL ingakwazi "ukuhambisa" ama-microtubules ngokuhlanganisa nabo futhi ivikele ama-micronubule kusuka ekuhlukaniseni ama-chromosomes ngesikhathi sokuhlukaniswa kweseli, ngaleyo ndlela kuholele ekufeni kwamangqamuzana omdlavuza, ikakhulukazi amangqamuzana omdlavuza [1]. Ngaphezu kwalokho, ngokwenza kusebenze ama-macrophage, i-tandol kubangela ukwehla ku-TNF-α (isimila neCrosis factor) receptors kanye nokukhishwa kwe-TNF-α, ngaleyo ndlela kubulale amaseli we-tumor [2]. Ngaphezu kwalokho, iTangerol ingakuheha i-apoptosis ngokwenza i-Apoptotic Receptor Pathay ethathwe yi-FAS / FASL noma isebenze uhlelo lokuvikela i-Cysteine [3]. Ngenxa ye-anticancer yayo ye-anticancer eminingi, iTatol isetshenziswa kabanzi ekwelapheni umdlavuza we-ovari, umdlavuza webele, umdlavuza wesisu, umdlavuza we-esophade, umdlavuza we-esophade, umdlavuza we-pest, melanoma, umdlavuza wentamo, njll [4]. Ikakhulu kumdlavuza webele osezingeni eliphezulu kanye nomdlavuza we-ovari athuthukile, i-taxOL inomphumela ovelele osele, ngakho-ke yaziwa ngokuthi "umugqa wokugcina wokuvikela ukwelashwa komdlavuza".
ITatoL iyisidakamizwa esidumile kunazo zonke emakethe yamazwe omhlaba eminyakeni yamuva futhi ibhekwa njengenye yezidakamizwa ezisebenza kahle zakwa-Anticancer zabantu eminyakeni engama-20 eyalandela. Eminyakeni yamuva nje, ngokukhula okuqhumayo kwabantu kanye nezehlakalomanvuza, isidingo se-tandol sikhule kakhulu. Njengamanje, i-TAXOL edingekayo yocwaningo lwezempilo noma lwesayensi ikhishwa ngokuqondile kusuka ku-TAXUS. Ngeshwa, okuqukethwe kwe-taxOL ezitshalweni kuphansi impela. Isibonelo, okuqukethwe kweTatol kungu-0,069% kuphela kumagxolo eTates Brevifolia, okuvame ukubhekwa njengokuqukethwe okuphezulu kakhulu. Ngokukhishwa kwe-1 g ye-taxOL, kudinga cishe ngo-13.6 kg wama-tables bark. Ngokusekelwe kulokhu kulinganisa, kuthatha izihlahla ezi-3 - 12 zamatekisi aneminyaka engaphezu kwengu-100 ubudala ukwelapha isiguli somdlavuza wesibeletho. Ngenxa yalokhu, inani elikhulu lezihlahla zamatekisi linqunywe phansi, okuholela ekuqothulweni okusondele kwalezi zinhlobo eziyigugu. Ngaphezu kwalokho, ama-tables ampofu kakhulu kwizinsizakusebenza futhi wephuza ukukhula, okwenza kube nzima ngokuthuthuka nokusetshenziswa kweTandol.
Njengamanje, inani eliphelele le-tandol liqediwe ngempumelelo. Kodwa-ke, indlela yayo yokwenziwa iyinkimbinkimbi kakhulu futhi ibiza kakhulu, iwenza kungabi yigugu lezimboni. Indlela ye-Semi-zokwenziwa yeTatol manje ivuthiwe futhi ibhekwa njengendlela ephumelelayo yokwandisa umthombo we-taxOL ngaphezu kokutshala okufakelwa. Kafushane nje, ngokuhlanganiswa kwe-tepol, i-taxrol prencesion compound okuchichimayo ezitshalweni zentela zikhishwa bese ziguqulwa zibe yi-taxtol nge-chemical synthesis. Okuqukethwe kwe-10-deacetylbaccatin ⅲ ngezinaliti zeTates Baccata kungaba ku-0,1%. Futhi izinaliti zilula ukuziphindaphinda ngokuqhathanisa nama-bark. Ngakho-ke, ukuhlanganiswa kwe-semi-kwe-tandol kususelwa ku-10-deacetylbaccatin ⅲ ukuheha ukunakwa okwengeziwe nokuningi okuvela kubacwaningi [5] (njengoba kukhonjisiwe kuMfanekiso 1).
Umdwebo 1. Indlela ye-Semi-Synthetic yeTandol esekwe ku-10-deacetylbaccatin ⅲ.
Kulokhu okuthunyelwe, okukhishwe isitshalo seTaxi Umhlangano womkhiqizo oqondiwe izidingo zokuhlanza izidingo zokuhlanza futhi zingasetshenziswa ekucwaningweni kwezesayensi okulandelayo, okunikeza isixazululo esisebenzayo sokuhlanzwa okusheshayo kwalolu hlobo lwemikhiqizo yemvelo.
| Into yokwenza utho | Umshini weSepabean ™ | |
| Igobolondo | I-12 g Sepaflash C18 RP Flash Carthridge (Spherical Silica, 20 - 45μm, Order Inombolo: SW-5222-012-SP) | |
| Umbuzi | 254 NM (ukutholwa), 280 nm (ukuqapha) | |
| Isigaba | Solvent a: amanzi | |
| Solvent b: methanol | ||
| Izinga Lokugeleza | 15 ml / min | |
| Ukulayisha isampula | Isampula engu-20 mg eluhlaza ichazwe ku-1 mL DMSO | |
| I-gradient | Isikhathi (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 | |
Imiphumela nengxoxo
I-Flash Chromatograph yesikhishwe esiqhekekile kusuka ku-Tables yaboniswa kuMfanekiso 2. Ngokuhlaziya i-Chromatograph, umkhiqizo oqondiwe kanye nokungcola okutholakele ukwahlukana okuyisisekelo. Ngaphezu kwalokho, ukuvela kabusha okuhle kwatholakala futhi ngemijovo yesampula eminingi (idatha ayikhonjiswa). Kuzothatha cishe amahora ama-4 ukuqedela ukwahlukana ngendlela ebonakalayo ye-chromatography ngekholomu yengilazi. Ukuqhathanisa indlela yendabuko ye-Chromatography Chromatography, indlela ezenzakalelayo yokuhlanza kulokhu okuthunyelwe idinga kuphela imizuzu engama-44 ukuqedela umsebenzi wonke wokuhlanza (njengoba kukhonjisiwe kuMfanekiso 3). Bangaphezu kuka-80% wesikhathi futhi inani elikhulu le-solvent lingagcinwa ngokuthatha indlela ezenzakalelayo, enganciphisa ngempumelelo izindleko futhi zithuthukise kakhulu ukusebenza kahle emsebenzini.
Umdwebo 2. I-flash chromatogram ye-crude ekhishwe kwi-tables.
Umdwebo 3. Ukuqhathanisa indlela ye-Chromatography ye-Chromatography ngendlela ezenzakalelayo yokuhlanza.
Ekuphetheni, ukuhlanganisa ama-cartridge e-sepaflash C18 RP ngomshini we-Sepabean ™ anganikeza isixazululo esisheshayo nesisebenzayo sokuhlanzwa okusheshayo kwemikhiqizo yemvelo efana nokukhishwa kwentela.
Ukunqubekela phambili
1. I-Alushin GM, I-Lander GC, KELLGG EH, Zhang R, Baker D kanye NOGALES E. Izilungiselelo eziphezulu ze-microtuvule zembula izinguquko ezihlelekile ku-αtp-tubulin ku-GTP hydrolysis in gp hydrolysis in gp hydrolysis. Iseli, 2014, 157 (5), 1117-1129.
2. Burkhart ca, Berman JW, Swindell CS neHorwitz sb. Ubudlelwano phakathi kwesakhiwo seTandol nezinye izintela ekungenisweni kwezimpawu ze-tumor necrosis factor-α gene gene shop ne-cytotoxicity. Ucwaningo lomdlavuza, 1994, 54 (22), 5779-5782.
3. Ipaki SJ, wu Ch, Gordon Jd, Zhong X, Emami A noSafa AR. I-taxlol ikhipha i-apoptosis ethembekile ye-caspase-10, J. biol. I-CHEM., 2004, 279, 51057-51067.
4. I-Paclitaxel. I-American Society of Health-System Sokhemisi. [Januwari 2, 2015]
5. UBruce Ganem noRoland R. Franke. I-PacliTaxel evela kuma-tatanes amabanga aphansi: umbono wokuqamba kokudala ku-organozincrosnonium chemistry. J. Org. UChem., 2007, 72 (11), 3981-3987.
Kunochungechunge lwama-cartridgeges weSepaflash C18 RP anezincazelo ezihlukile ezivela kubuchwepheshe beSantai (njengoba kukhonjisiwe kuThebula 2).
| Inombolo yento | Usayizi wekholomu | Izinga Lokugeleza (ml / min) | Max.prestrure (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 |
Ithebula 2. I-Sepaflash C18 RP Flash Cartridges.
Ukupakisha izinto: I-Silica enamandla amakhulu we-C18-Bonded, 20 - 45 μm, 100 Å
Ngeminye imininingwane ngokucaciswa okunemininingwane yomshini we-Sepabean ™, noma imininingwane yoku-oda ku-Sepaflash Series Flart Cartridges, sicela uvakashele iwebhusayithi yethu
Isikhathi sePosi: Sep-20-2018