Meiyuan Qian, Yuefeng Tan, Bo Xu
Codsiga Xarunta R&D
Hordhac
Taxus (Taxus chinensis ama Chinese yew) waa dhir duurjoogta ah oo wadanku ilaaliyo.Waa geed naadir ah oo halis ah oo ay ka tageen barafka Quaternary.Sidoo kale waa dhirta kaliya ee daawaynta dabiiciga ah ee adduunka.Taxus waxaa loo qaybiyaa aagga dhexdhexaadka ah ee hemisphere waqooyi ilaa bartamaha-hoosaadka gobolka, oo leh ilaa 11 nooc oo adduunka ah.Dalka Shiinaha waxaa ka jira 4 nooc iyo 1 nooc oo kala ah Taxus Waqooyi Bari, Yunnan Taxus, Taxus, Taxus Tibetan iyo Koonfurta Taxus.Shantan nooc ayaa lagu kala qaybiyaa Koonfur-galbeed Shiinaha, Koonfurta Shiinaha, Shiinaha badhtamaha, Shiinaha bari, Waqooyi-galbeed Shiinaha, Waqooyi-bari Shiinaha iyo Taiwan.Dhirta Taxus waxay ka kooban tahay noocyo kala duwan oo kiimiko ah, oo ay ku jiraan taxaxayaal, flavonoids, lignans, steroids, phenolic acids, sesquiterpenes iyo glycosides.Daawada caanka ah ee ka hortagga burooyinka Taxol (ama Paclitaxel) waa nooc ka mid ah canshuuraha.Taxol waxay leedahay habab gaar ah oo ka hortagga kansarka.Taxol waxay "barafeyn kartaa" microtubules iyaga oo isku daraya iyaga oo ka hortagaya microtubules inay kala soocaan koromosoomyada wakhtiga qaybta unugyada, taas oo horseedaysa dhimashada unugyada qaybsan, gaar ahaan unugyada kansarka oo si degdeg ah u fidiya.Intaa waxaa dheer, iyada oo la kicinayo macrophages, Taxol waxay keentaa hoos u dhac ku yimaada TNF-α (cudurka necrosis factor) iyo sii deynta TNF-α, taas oo dila ama la joojiyo unugyada burooyinka [2].Waxaa intaa dheer, Taxol waxay keeni kartaa apoptosis adoo ku dhaqmaya dariiqa soo-dhoweynta apoptotic ee dhexdhexaadinta Fas / FasL ama kicinta nidaamka protease cysteine [3].Sababtoo ah saameynteeda badan ee bartilmaameedka anticancer, Taxol waxaa si weyn loogu isticmaalaa daaweynta kansarka ugxan-sidaha, kansarka naasaha, kansarka sambabada unugyada aan-yare ahayn (NSCLC), kansarka caloosha, kansarka hunguriga, kansarka kaadiheysta, kansarka qanjirka 'prostate', melanoma malignant, madaxa iyo qoorta. kansarka, iwm[4].Gaar ahaan kansarka naasaha ee horumarsan iyo kansarka ugxan-sidaha, Taxol waxay leedahay saameyn daweyn oo heer sare ah, sidaas darteed waxaa loo yaqaan "khadka ugu dambeeya ee daaweynta kansarka".
Taxol waa dawada ugu caansan ee ka hortagga kansarka ee suuqyada caalamiga ah sannadihii u dambeeyay, waxaana lagu tiriyaa inay tahay mid ka mid ah daawooyinka ugu waxtarka badan ee ka hortagga kansarka ee bini'aadamka 20-ka sano ee soo socda.Sanadihii la soo dhaafay, iyada oo korodhka qarxa ee dadweynaha iyo dhacdooyinka kansarka, baahida loo qabo Taxol ayaa sidoo kale kor u kacday.Waqtigan xaadirka ah, Taxol looga baahan yahay cilmi-baaris caafimaad ama cilmi-baaris ayaa inta badan si toos ah looga soo saaraa Taxus.Nasiib darro, waxa ku jira Taxol ee dhirta waa mid aad u hooseeya.Tusaale ahaan, nuxurka Taxol waa 0.069% oo kaliya ee jilifta Taxus brevifolia, taas oo guud ahaan loo arko inay leedahay nuxurka ugu sarreeya.Si loo soo saaro 1 g oo Taxol ah, waxay u baahan tahay qiyaastii 13.6 kg oo jilif Taxus ah.Iyada oo ku saleysan qiyaastan, waxay qaadanaysaa 3 - 12 geedo Taxus ah oo ka weyn 100 sano si loo daweeyo bukaanka kansarka ugxan-sidaha.Taasi waxay keentay in geedo badan oo Taxus ah la jaro, taas oo keentay in uu dabargo’o nooca qaaliga ah.Intaa waxaa dheer, Taxus waa mid aad u liidata xagga kheyraadka iyo kobaca dhaqaalaha, taas oo adkeynaysa horumarinta iyo ka faa'iidaysiga cashuurta.
Waqtigan xaadirka ah, wadarta guud ee Taxol si guul leh ayaa loo dhameeyay.Si kastaba ha ahaatee, dariiqeeda synthetic waa mid aad u adag oo qaali ah, taas oo ka dhigaysa mid aan muhiimad warshadeed lahayn.Habka semi-synthetic ee Taxol hadda waa bislaaday waxaana loo arkaa inay tahay hab wax ku ool ah oo lagu ballaariyo isha Taxol marka lagu daro beeritaanka macmalka ah.Si kooban, qayb-isku-dhafka Taxol, xarunta hore ee Taxol oo aad ugu badan dhirta Taxus ayaa la soosaaraa ka dibna loo beddelaa Taxol iyadoo la adeegsanayo isku-dhafka kiimikada.Waxa ku jira 10-deacetylbaccatin Ⅲ ee cirbadaha Taxus baccata waxay noqon kartaa ilaa 0.1%.Oo cirbadaha waa sahlan tahay in dib loo soo celiyo marka la barbardhigo jilifyada.Sidaa darteed, isku-dhafka Taxol ee ku salaysan 10-deacetylbaccatin Ⅲ ayaa soo jiidanaya dareen badan oo cilmi-baarayaasha[5] (sida ku cad sawirka 1).
Jaantuska 1. Jidka semi-synthetic ee Taxol ee ku salaysan 10-deacetylbaccatin Ⅲ.
Boostada dhexdeeda, soosaarka geedka Taxus waxaa lagu sifeeyay nidaamka chromatography dareere ah ee u diyaargaroobaya ee SepaBean ™ mashiinka oo ay weheliso SepaFlash C18 reverseed-phase (RP) kartoonada ay soo saartay Santai Technologies.Badeecada bartilmaameedka ah ee buuxinaysa shuruudaha daahirsanaanta ayaa la helay waxaana loo isticmaali karaa cilmi-baaris cilmi-baariseed oo xiga, oo bixisa xal-wax-ku-ool ah oo loogu talagalay nadiifinta degdegga ah ee noocyadan dabiiciga ah.
| Qalabka | SepaBean™ mashiinka | |
| Kartridge | 12 g SepaFlash C18 RP flash cartridge (silica wareegsan, 20 - 45μm, 100 Å, lambarka dalbashada: SW-5222-012-SP) | |
| Mawjada dhererka | 254 nm (ogaanshaha), 280 nm (kormeerka) | |
| Marxaladda mobilada | Walxaha A: Biyo | |
| Xalka B: Methanol | ||
| Heerka socodka | 15 ml/min | |
| Muunad rarista | 20 mg muunad cayriin ah oo lagu milmay 1 mL DMSO | |
| Gradient | Waqtiga (min) | Miraha B (%) |
| 0 | 10 | |
| 5 | 10 | |
| 7 | 28 | |
| 14 | 28 | |
| 16 | 40 | |
| 20 | 60 | |
| 27 | 60 | |
| 30 | 72 | |
| 40 | 72 | |
| 43 | 100 | |
| 45 | 100 | |
Natiijooyinka iyo dood
chromatogram-ka tooska ah ee ka-soo-saarka cayriin ee Taxus ayaa lagu muujiyay sawirka 2. Marka la falanqeeyo chromatogram-ka, badeecada la beegsanayo iyo wasakhda ayaa la gaaray kala-soocidda aasaasiga ah.Intaa waxaa dheer, taranka wanaagsan ayaa sidoo kale lagu ogaaday irbado muunado badan (xog aan la muujin).Waxay qaadan doontaa ilaa 4 saacadood in lagu dhammaystiro kala-soocidda habka chromatography-ga gacanta ee leh tiirar dhalo ah.Marka la barbar dhigo habka chromatography-ga gacanta ee soo jireenka ah, habka nadiifinta tooska ah ee ku jira qoraalkan wuxuu u baahan yahay 44 daqiiqo kaliya si loo dhammeeyo hawsha nadiifinta oo dhan (sida ku cad sawirka 3).In ka badan 80% wakhtiga iyo xaddi badan oo dareere ah ayaa lagu badbaadin karaa iyadoo la qaadanayo habka tooska ah, kaas oo si wax ku ool ah u yareeyn kara qiimaha iyo sidoo kale si weyn u hagaajinaya waxtarka shaqada.
Jaantuska 2. Kormatogaraamka toosh ee laga soosaaray Taxus.
Jaantuska 3. Isbarbardhigga habka chromatography-ga gacanta iyo habka nadiifinta tooska ah.
Gabagabadii, isku darka SepaFlash C18 RP flash cartridges mashiinka SepaBean ™ wuxuu ku siin karaa xal degdeg ah oo hufan sifeynta degdega ah ee alaabada dabiiciga ah sida soosaarka Taxus.
Tixraacyo
1. Alushin GM, Lander GC, Kellogg EH, Zhang R, Baker D iyo Nogales E. Qaab-dhismeedka microtubule-xalinta sare waxay muujinayaan kala-guurka qaabdhismeedka αβ-tubulin ee GTP hydrolysis.Unug, 2014, 157 (5), 1117-1129.
2. Burkhart CA, Berman JW, Swindell CS iyo Horwitz SB.Xidhiidhka u dhexeeya Qaab dhismeedka Taxol iyo Cashuuraha Kale ee Ku Saabsan Soo-saarka Tumor Necrosis Factor-α Muujinta Hiddaha iyo Cytotoxicity.Cilmi-baarista Kansarka, 1994, 54 (22), 5779-5782.
3. Park SJ, Wu CH, Gordon JD, Zhong X, Emami A iyo Safa AR.Taxol waxay keentaa Apoptosis-ku-tiirsanaanta Caspase-10, J. Biol.Chem., 2004, 279, 51057-51067.
4. Paclitaxel.Ururka Farmashiyeyaasha Nidaamka Caafimaadka ee Maraykanka.[Janaayo 2, 2015]
5. Bruce Ganem iyo Roland R. Franke.Paclitaxel oo ka socda Taxanes-ka aasaasiga ah: Aragtida Hal-abuurka Hal-abuurka ee Organozirconium Chemistry.J. Org.Chem., 2007, 72 (11), 3981-3987.
Waxaa jira taxane ah kartoonada flash-ka ee SepaFlash C18 RP oo leh tilmaamo kala duwan oo ka yimid Tignoolajiyada Santai (sida ku cad Shaxda 2).
| Lambarka Shayga | Cabirka tiirka | Heerka socodka (ml/min) | Ugu badnaan.cadaadiska (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 |
Shaxda 2. SepaFlash C18 RP flash cartridges.
Qalabka wax lagu xidho: Silica-spherical C18-ku-xidhan oo tayo sare leh, 20 - 45 μm, 100 Å
Macluumaad dheeri ah oo ku saabsan faahfaahinta faahfaahsan ee mashiinka SepaBean™, ama dalabka macluumaadka ku saabsan kartoonada taxanaha ah ee SepaFlash, fadlan booqo shabakadayada
Waqtiga boostada: Sep-20-2018