Phan lap va xae dinh cSu true tectoridin va 0 lB,3B-dihydroxylup-20(29)-entir
cay soi rirng {Sarcandra glabra Thunb.)
Mai Thi Hai Yen', Nguyen Duy Thuan', Chau Van Minh^ Pham Hai Yln^ Phan Van Kiem^
' Vi^n Dugc lieu, Bg Yte
^Vien Hoa hoc cdc Hgp chdt Thien nhien, Vien Khoa hoc vd Cong nghe Viet Nam Dat van de
Cdy s6i arng {Sarcandra glabra (Thunb.) Nakai) id loai cay nhd eao 1-2m; nhdnh trdn, khOng long, mpc ddi. Ld mpc ddi, cd phiin ddi xoan biu due, ddi 7-1 Sem, r6ng 2-7cm, diu nhpn, mdp ed rdng nhpn, gdn phu 5 cdp; eudng ngdn 5-8mm. Bdng kdp, it nhdnh, nhdnh ngdn; hoa nhd, mdu trdng, khdng cudng; nhj 1. Qua nhd mdu dd gaeh, mpng, gin trdn 6x4 mm. Cdy ra hoa vdo thdng 6-7 vd cd qua vdo thdng 8-9. Cdy dugc sir dung trong ddn igian d i chua nhiiu benh nhu ung thu tuy, da ddy, true trdng, gan, cudng hpng; viem ndo B tmyen nhiem;
ly true tnjng; vidm rudt thua cip, benh nhpt; gdy xuang, thip khdp tang khdp, dau lung '^"^'. Cdc nhd khoa hpe Trung Qude dd bdt diu nghien ciru cay thudc ndy tu ndm 1988'^' vdi viee tim ra hgp ehit sesquiteepen mdi. Nhiiu cdng bd sau d6 dd cho thiy thdnh phin hda hpc chu yeu cua cdy S.
glabra Id sesquiterpene lacton''*'^, cunnarin'®', flavonoid'^, triteepenoid'^'. Hoat tinh rit ddng chu y dd Id kha ndng chdng viem'®', chdng ung thu '^°', ha huyet dp'"' eua djch chiet methanol cua cdy thudc ndy. Cy Viet Nam vin chua cd nhieu c6ng trinh nghien euu v i thdnh phan hda hpc vd hoat tinh sinh hpc cua cdy ndy. Bdi bdo ndy th6ng bdo kit qua phdn ldp vd xdc dinh cau trOc hda hpc cue cdc hgp chit flavonoid (tectoridin) vd tritecpen (ip,3P- dihyclroxylup-20(29)-en) tu djch chiit methanol cua cdy* S. glabra. Ddy Id lin diu tien cdc hgp chit ndy dugc phdn ldp tu edy sdi rtrng.
Vat lieu va Phu'O'ng phap nghien
CU'U
Mlu thu'c vat
Mdu cdy sdi rung {Sarcandra glabra (Thunb.) Nakai) dugc thu hdi tai nui cao Tam Dao vd
Tram nghien cuu trdng cdy thudc Tam Oao, Vinh Phuc, vdo thdng 9 vd thdng 10 ndm 2009, ru'a sgeh, phoi siy khd vd duge bao quan noi kh6 rdo d i nghien euu...
Phu'O'ng phap nghien ciru
Phwang phap phan lap cac hap chat
sic ky ldp mdng (TLC): Sde ky ldp mdng duge thue hien tren ban mdng trdng sdn DC- Alufolien 60 F254 (Merck 1,05715), RP18 F254s (Merck). Phdt hien chit bang den tu' ngoai a hai bude sdng 254 nm vd 365 nm hode diing thude thu Id dung djeh H2S04 10% Suae phun diu l§n ban mdng, say khd rdi hg ndng tren bep dien tu tu den khi hien mdu.
Sdc ky e6t (CC): Sde ky ept duge tiin hdnh vdi chat hip phu Id Silica gel pha thud'ng vd pha dao. Silica gel pha thudng cd c6' hat Id 0,040-0,063 mm (240-430 mesh). Silica gel pha dao YMC (30-50 nm, Fujisilisa Chemical Ltd.).
Phwang phap xae djnh cau true hoa hoc cac hap chat
Diim ndng chiy do tren mdy Kofler micro- hotstage
Phd khdi lugng phun mu dien tCr (Electrospray Ionization mass spectra) dugc do tren mdy AGILENT 1100 LC-MSD Trap. •
Phd cdng hudng tiu nhin NMR dugc do tren mdy Bruker AM500 FT-NMR Spectrometer.
Phan lap hvp chit
Dung 5 kg mdu cdy sdi rung {Sarcandra glabra) khd dugc chiet ba lin vd'i 10 lit methanol.
Cdc djeh chiet sau dd dugc loai dung moi thu dugc 140 g cdn chiit MeOH. C$n MeOH duge hda vdo 21 nude vd chiet phan Idp lan lugt vdi cdc dung m6i cd dd phdn cue tdng dan Id n-hexan, eloroform, EtOAc, n-BuOH de thu dugc cdc dich
TAP CHi DU'QC HQC - 8/2010 (SO 412 NAM 50) 45
• Nghien CLFU - Ky thuat
c6 n-hexan (18g), cloroform (30g), EtOAe (25g), n-BuOH (15g) vd ldp nude. Djch chiit nude duge tiin hanh phdn lap tren sde ky ept DIANION HP- 20 su dung dung m6i rira giai Id MeOH/H20 (25/75, 50/50, 75/25, 100/0). Sau khi loai dung moi thu dugc cae can tuang irng lan lugt Id 25%
MeOH (9g), 50% MeOH (15g), 75%MeOH (12g) va 100%MeOH (lOg), Phdn doan 50% MeOH (15g) dugc tiin hdnh phan lap tren sdc ky ept nhdi silica gel vdi he dung moi cloroform/aeeton (8/1, 1,5 L) thu duge hgp ehit HS1B1A (15mg), Phan doan 75%MeOH (12g) duge tiin hanh phan lap tren sic ky ept nhdi silica gel vdi he dung mdi cloroform/methanol/nude (70/30/4, 1,5 1) thu dugc hgp ehit HS2C1B(18mg),
Tectorigenin 7-glucosid- tectoridin (HS2C1B) (chat 1)
Chit bpt kh6ng mdu, Nhiet dp ndng ehay
256-257 °C,
Phd ESI-MS m/z 463 [M+H]^ 461 [M-H]", Cdng thuc phdn t u C22H22O11. Khdi lugng phan tu M= 462.
'H-NMR (500 MHz, Py-de) 6 (ppm): 8,10 (d, J = 2,0 Hz, H-2), 7,17 (s , H-8), 7,68 (d, J = 8,0 Hz, H-2', H-6'), 7,27 (d, J = 8,0 Hz, H-3', H-5'), 5,80 (d, J = 7,5 Hz, H-1"), 4,38 (H-2"), 4,22 (H- 3"), 4,30 (H-4"), 4,38 (H-5"), 4,61 (d, J = 12,0 Hz, Ha-6"), 4,38 (Hb-6") vd 4,04 (s, OCH3).
^^C-NMR (125 MHz, Py-ds) 5 (ppm): 153,91 (C-2), 123,79 (C-3), 181,67 (C-4), 154,45 (C-5), 133,82 (C-6), 157,63 (C-7), 94,86 (C-8), 153,31 (C-9), 107,74 (C-10), 122,11 (C-1'), 130,98 (C-2', C-6'), 116,35 (C-3', C-5'), 159,33 (C-4'), 102,08 (C- 1"), 74,69 (C-2"), 79,41 (C-3"), 71,25 (C-4"), 78,38 (C-5"), 62,51 (C-6") vd 60,78 (OCH3).
2f HO
HO "
Hinh 1. Cau true hoi hoc cua 1 - 2
1 P,3p-Dihydroxylup-20(29)-en (HS1B1A) (chat 2)
Tinh t h i hinh kim co mau trdng. Nhiet dp nong ehay 251-252 °C.
ESI-MS m/z 443 [M+Hf, 441 [M-H]", Cdng thue phan tip C30H50O2. Khdi lugng phdn tu M= 442
^H-NMR (500 MHz, CDCI3) 5 (ppm): 4,45 (IH, dd, J = 11,5, 5,0 Hz, H-1), 1,63 (1H,m, Ha-2), 1,85 (1H, m, Hb-2), 3,26 (IH, dd, J = 12,0, 2,0, H-3), 0,60 (1H, dd, J = 6,5, 2,0, H-5), 1,54 (1H, m, Ha-6), 1,59 (IH, m, Hb-6), 1,40 (2H, m, H-7), 1,53 (IH, m, H-9), 1,40 (IH, m, Ha-11), 2,21 (IH, m, Hb-11), 1,18 (IH, m, Ha-12), 1,62 (1H, m, Hb-12), 1,69 (IH, m, H-13), 1,68 (IH, m, Ha-15), 1,70 (IH, m, Ht- 15), 1,54 (2H, m, H-16), 1,37 (IH, H-18), 2,40
(IH, m, H-19), 1,35 (1H, m, Ha-21), 1,96 (IH, m, Hb-21), 1,21 (IH, m, Ha-22), 1,41 (IH, m, Hb-22), 1,00 (3H, s, H-23), 0,77 (3H, s, H-24), 0,92 (3H, s, H-25), 1,06 (3H, s, H-26), 0,97 (3H, s, H-27), 0,81 (3H, s, H-28), 1,71 (3H, s, H-29), 4,70 (IH, d, J = 2,0 Hz, Ha-30) vd 4,58 (1H, dd, J = 2,0, 1,5, Hb-30),
^^C-NMR (125 MHz, CDCI3) 5 (ppm): 79,04 (C-1), 38,12 (C-2), 75,77 (C-3), 38,91 (C-4), 53,18 (C-5), 18,02 (C-6), 34,17 (C-7), 41,42 (C- 8), 51,54 (C-9), 42,94 (C-10), 23,87 (C-11), 25,16 (C-12), 37,64 (C-13), 42,94 (C-14), 27,57 (C-15), 35,65 (C-16), 43,64 (C-17), 48,39 (C- 18), 48,01 (C-19), 150,82 (C-20), 29,82 (C-21), 40,03 (C-22), 27,87 (C-23), 14,94 (C-24), 11,89 (C-25), 16,27 (C-26), 14,48 (C-27), 18,06 (C- 28), 19,25 (C-29) vd 109,45 (C-30),
46 TAP CHi DLTQC HQC - 8/2010 (SO 412 NA^. 1)
K i t qua va thao luan
Phd NMR eiia hgp ehit HS2C1B ed dang phd eua mpt flavonoid glycosid vdi cdc tin hieu d d e t r u n g t a i 5 8,10(1H, s, H-2), 7,17 ( I H ; s , H- 8) vd vdng B t h i para tai 5 7,68 (2H, d, J = 8,0 Hz, H-2', H-6'), 7,27 (2H, d, J = 8,0 Hz, H-3', H- 5'); tin hieu proton anome cua dudng glucose tai 5 5,80 (d', J = 7,5 Hz, H-1"), vd tin hieu cua nhom metylen ndi vdi oxi tai 6 4,61 (d, J = 12,0 Hz, Ha-6") va 4,38 (Hb-6"). Tin hieu H-2 djeh ehuyin r i t manh v i phia trudng t h i p (5 8,10) eho thiy carbon metin C-2 phai ndi vdi nguyen tir oxi, chung td hgp ehit isoflavon. Ngodi tin hieu singlet eiia H-2 thi tin hieu singlet con lai (5 7,17) ehung td ring vong A bi t h i ca 5 vj tri, Ngoai ra edn cd tin hieu cua mpt nhdm metoxi tai 5 4,04 (3H, s), Gid trj hdng sd tuang tdc spin- coupling giua H-1" va H-2" eua phdn t u dudng ehung td chiing d i u chiim vj tri equatorial va nhu vdy tdn tai lien k i t 0-P-glueose. Tren phd
^^C-NMR xuit hien tin hieu ciia 22 nguyen t u eaebon, trong do vong B ed hai tin hieu CH ed eudng dp eao tai 5 130,98 (C-2', C-6'), 116,35 (C-3', C-5'), vd tren phd HSQC hai tin hieu ndy CO pie giao vdi cdc proton tuang ung tai 5 7,68 (d, J = 8,0 Hz, H-2', H-6'), 7,27 (d, J = 8,0 Hz, H- 3', H-5') khang dinh them vong B t h i para. Tin hieu eua nhom earbonyl duge nhan b i i t tai 5 181,67 (C-4), nhom metoxi tai 5 60,78 va tin hieu CH dich chuyin manh v i phia trudng t h i p 5 153,91 (C-2) cung khang djnh day Id isoflavon, Cdc tin hieu ciia phdn tir dudng glucose ddc trung tai 5 102,08 (C-1"), 74,69 (C-2"), 79,41 (C- 3"), 71,25 (C-4"), 78,38 (C-5"), 62,51 (C-6").
Nhdm metoxi ndi vdo C-6 bdi tuang tdc HMBC giua cdc tin hieu proton 5 4,04 vdi C-6 (5 133,82) vd proton H-8 (5 7,17) vdi C-6. Phdn tu' dudng ndi vdo C-7 bdi tuong tdc HMBC giua proton H-1" (6 5,80) vol carbon C-7 (§ 157,63).
Han nua, ede gid trj dp djch chuyen hda hpe eua C-5, C-6 vd C-7 tuang ung Id 154,45, 133,82 vd 157,63 phii hgp vgi quy luat ciia hieu ung mdi nhd vd du kien dd eong bd eho hgp ehit tectoridin '^^', cac tuang tdc HSQC vd HMBC dd dugc phan tich chi tiit. K i t qua eho thiy hgp c h i t HS2C1B ehinh Id tectoridin '^^l K i t qua ndy cdn dugc khang djnh bdng phd khdi lugng vdi su xuat hien pic ion 463 [M+Hf (positive ion mode) va pie 461 [M-H]" (negative
ion mode) tren phd ESIMS. Hgp c h i t tectoridin ed boat tinh uc e h i khd tdt su phat triin eua mpt sd ddng t i bdo ung thu thue nghiem nhu ddng P388 (ED5o=0,31 mM), L1210 (ED5o= 0,04 mM), SNU C4 (ED5o=0,40 mM) ' " I Tectoridin da duge tim thiy t u lodi Pueraria thunbegiana (Leguminosae) '^^' nhung day la l i n d i u tien duge phdn lap t u cay sdi rung. K i t qua neu tren cho thiy, vgi s u ed mat eua hgp e h i t tectoridin va kha ndng uc c h i khd tdt s u phdt triin eua mpt sd dong t i bao ung thu tren in vitro eung co the giai thich d u g c viec sir dung cay thudc ndy trong ddn gian, ddc biet Id trong thdi gian g i n ddy.
Phd NMR eua HS1 B I A eo dang phd eua mpt hgp c h i t tritecpen vdi cdc tin hieu ehu y i u ndm trong vung t u 5H 0,5 ppm d i n 2,5 ppm, ddc biet Id su x u i t hien cua 7 tin hieu singlet eua 7 nhom methyl tai 5 1,00 (3H, s, H-23), 0,77 (3H, s, H- 24), 0,92 (3H, s, H-25), 1,06 (3H, s, H-26), 0,97 (3H, s, H-27), 0,81 (3H, s, H-28), 1,71 (3H, s, H- 29) tren phd ' ' H - N M R . Cung tren phd nay, s u x u i t hien eiia hai tin hieu tai 5 4,70 ( I H , d, J = 2,0 Hz, Ha-30), 4,58 ( I H , dd, J = 2,0, 1,5, Hb-30) ciing vdi tin hieu cua nhdm metyl singlet djch ehuyen manh v i phia trudng t h i p ban cho thiy su cd mat cua ndi ddi C-20/C-29 eua khung lupan '^'*', Hai proton tai 5 4,45 (1H, dd, J = 11,5, 5,0 Hz, H-1) vd 1,85 ( I H , m, Hb-2), 3,26 (1H, dd, J = 12,0, 2,0, H-3) Chung td s u ed mat eua hai nhdm hydroxy, Nhu vdy, sa bp ed the nhdn djnh hgp c h i t HS1B1A Id mpt lupan c6 ndi ddi C- 20/C-29 vd hai nhdm hydroxy, Thdng thudng vdi cdc hgp ehit lupan, cac nhom hydroxy x u i t hien tai ede vj tri C-1, C-2, hode C-3. N i u hai nhdm hydroxy nam g C-2 vd C-3 thi tin hieu cpng hudng eua H-3 ehi cd the Id doublet hoac broad singlet, Tuy nhien proton H-3 d day xuat hien la mpt doublet ciia mpt doublet {J = 12,0, 2,0 Hz) chung td C-2 khOng eo nhdm the ndo, vd nhu vdy ed the nhdm hydroxy se ndm d C-1, Phd "C-NMR cua HS1B1A x u i t hien 30 tin hieu ciia mpt tritecpen, trong dd eae loai carbon C, CH, CH2, CH3 dugc xde dinh bdng ede phd DEPT 135 va DEPT 90. Ndi doi C-20/C-29 cua khung lupan dugc xdc djnh tai 5 150,82 (C) vd 109,45 (CH), hai carbon CH ndi vdi nhdm hydroxy dugc xae djnh tai 5 79,04 va 75,77, bay nhom metyl tai 5 27,87 (C-23), 14,94 (C-24), 11,89 (C-25), 16,27 (C-26), 14,48 (C-27), 18,06
TAP CHi DUOC HOC - 8/2010 (SO 412 NAM 50) 47
• Nghien CLFU - Ky thuat
(C-28), 19,25 (C-29). Vdi khung lupan, cap bdn tin hieu CH khd d i i n hinh tai 5 53,18 (C-5), 51,54 (C-9) 48,39 (C-18), 48,01 (C-19) ddng thdi hai nhdm hydroxy xde djnh tai C-1 vd C-3 cung vdi e i u hinh p boi gid trj dp djeh ehuyen hda hpe ddc trung tai 5 79,04 vd 75,77 '^"l Cdc du kien phd NMR cua HS1B1A dugc xdc djnh d i u tien dua vdo su so sdnh vdi cdc du kien phd NMR tuang irng ciia 1|3,3|3-dihydroxylup- 20(29)-en '^''' vd eho k i t qua r i t phii hgp. Bdng cdc phd HSQC, tu cac gid trj dp djch chuyin carbon, xde dinh duge cae proton tung irng vdi tung carbon, Phd HMBC cung dugc do de xde djnh chinh xde ede gid trj dd djch ehuyin hoa hpe eua tung vj tri cung nhu khdng djnh chinh xde hai nhom hydroxy tai C-3 vd C-1. K i t qua nay duge chung minh bdng tuang tde HMBC
cua H-25 (5 0,92) vdi carbon C-1 (5 79,04), cung nhu cua H-23 (5 1,00) vd H-24 (5 0,77) ddng thdi c6 tuang tae vdi C-3 (5 75,77). Hoa hpe lap the eua nhom hydroxy tai C-1 vd C-3 cung dugc khang djnh Id 1/3,3j3 bdi s u phu hgp hodn todn ve dp djch chuyin h6a hpe proton, carbon cung nhu gid trj hdng sd tuang tdc spin-coupling giua H-1/H-2/H3 eua hgp ehit HS1 B I A vgi ede gid trj tugng ung eiia tuong ung eua 1/3,3/3- dihydroxylup-20(29)-en '''"l Ngodi ra, k i t qua phd khdi ESI-MS x u i t hien pie ion m/z 443 [M+H]*, 441 [M-H]" hodn toan tuang ung vdi eong thue phdn tir C30H50O2. T u nhung phdn tieh neu tren, hgp e h i t HS1B1A duge khdng djnh Id 1/3,3/3-dihydroxylup-20(29)-en. Ddy Id lin d i u tien hgp c h i t ndy dugc tim thiy tir cdy soi rung. . ,,
H O '
1 2 Hinh 2: iWpf sd tuang tie ehinh tren phd HMBC cuai -2
Ket luan
Bdng cdc phuong phap sde ky k i t hgp, cdc hgp chit flavonoid (tectoridin) va tritecpen (ip,3p-dihydroxylup-20(29)-en) dd duge phdn lap tu djch chiit methanol ciia edy S. glabra.
c i u triie hoa hpc eua ehiing dugc xde dinh bdng cdc phuang phdp phd NMR, phd MS vd so sdnh vdi cac du kien phd dd eong bd. Ddy Id l i n d i u tien cac hgp c h i t nay duge phdn lap tir edy soi rung, Ddng ehii y Id viee phdt hien hgp c h i t tectoridin cd mat trong cdy sdi rung vd nd dd duge chirng minh Id co kha ndng ue e h i khd tdt su phat triin cua mpt sd ddng t i bdo ung thu tren md hinh in vitro.
Summary
From the aerial part of S. glabra three compounds, e.g. chloranoside A, tectoridin and
1 li,3p-dihydroxylup-20(29)-en, were isolated by various chromatography techniques. Their
structures were identified by the analysis of their ESI-MS, ID- and 2D-NMR spectra in refference to the literature values. This is the first report of these three compounds from the Vietnamese S.
glabra.
Tai lieu tham khao
1. Bd Tat Lgi, Nhung cay thudc va vj thuoe Viet Nam, Nha xuat ban Y hge Ha Ngi (2001).
2. Do Huy Bich va cong su, Cay thuoe va dpng vat lam thuoe a Viet Nam, Tap II, Nha xuat ban Khoa hoc va Ky thuat (2004).
3. Wang AQ, Feng SC, He X, Xu RS. A new sesquiterpene lactone from Sarcandra glabra, Yao Xue Xue Bao. (1988) Vol. 23(1):64-66.
4. Zhu LP, Li Y, Yang JZ, Zuo L, Zhang DM, Two new sesquiterpene lactones from Sarcandra glabra. J Asian Nat Prod Res. (2008) 10(5-6):541-545.
5. Hu XR, Yang JS, Xu XD. Three novel sesquiterpene glycosides of Sarcandra glabra. Chem Pham) Bull. (2009) Vol. 57(4):418-420.
(Xem tiep trang 19)
48 TAP CHi DU'QC HQC - 8/2010 (SO 412 NAM SO)
K i t qua tren cho t h i y dinatri EDTA lam eham qua trinh oxy hoa eiia pantoprazol, ham lugng pantoprazol ciia bpt dong kho pha e h i tu eong thue trong thanh p h i n ed dinatri EDTA eao ban eae m i u khong eo dinatri EDTA. K i t qua nay eung phu hgp vai nghien euu eua mpt sd tae gia tren t h i giai '^'.
K§t luan
TO nhung k i t qua nghien cuu, thue nghiem thu dugc, rut ra mpt sd k i t luan:
- pH eiia dung djeh anh hudng d i n dp dn djnh eua hoat chit pantoprazol.
- Bpt ddng kho khi sir dung manitol lam td duge dpn ed hinh thire dep va dn djnh ban so vdi sorbitol.
- Pantoprazol r i t d i bi oxy hda. Vi vay, trong eong thue thudc tiem ddng khd pantoprazol 40mg c i n phai ed ehit ehdng oxy hda.
Tren ea sd khao sat, da xdy dung duge eong thue thudc tiem dong khd pantoprazol 40mg vdi cac thanh phin: natri pantoprazol sesquihydrat natri hydroxyd, manitol, dinatri EDTA, nude e l t pha tiem.
Summary
A formulation of pantoprazole lyophilized injectable powder was developed. The solution pH value really affected the stability of pantoprazole;
the appearance of the lyophilized powder was finer and the stabibility was better with mannitol as bulking agent than sorbitol. Due to the oxidation- sensitivity of pantoprazole, any anti-oxidant agent should be necessary. The developed formulation
consisted of pantoprazole sodium sesquihydrate, sodium hydroxyde, mannitol, disodium EDTA and water for injection. Pantoprazole lyophilized injectable powder was prepared by the proposed methd at laboratory scale with batch size of 100 - 200 bottles each.
Tai lieu tham khao
1. Bp Y te, Dupc thu qudc gia, NXB Y hoc (2007), tr. 1278-1280.
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(2009), 35, p. 114-117.
4. C Scarpignato and R.H.Hunt, Proton pump inhibitors: the beginning of the end or the end of the beginning?, Current Opin. Pharmacol. (2008), 8, p.
677-684.
5. Frank Kofi Bedu-Addo, Understanding lyophilization formulation development, Pharm.
Technol. {2004). 2. p. 10-50.
6. R.P.Raffin et al, Gastro-resistant microparticles containing sodium pantoprazole; Stability studies and in vivo anti-ulcer activity. The Open Drug J. (2007), 1, p. 28-35.
7. Rudolf binder. Range Dietrich, Freeze-dried pantoprazole preparation and pantoprazole injection, http:www.FreshPatents.com, (2009)
8. T.Comoglu et al. Development and in vitro evaluation of pantoprazole-loaded micropheres. Drug De/. (2008), 15, p. 295-298.
N g h i e n C L P U . . . (Tiep trang48)
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2010 Jan 7. [Epub ahead of print]
7. Huang MJ, Zeng GY, Tan JB, Li YL, Tan GS, Zhou YJ. Studies on flavonoid glycosides of Sarcandra glabra, Zhongguo Zhong Yao Za Zhi.
(2008) Vol. 33(14);1700-1702.
8. Luo YM, Liu AH, Zhang DM, Huang LQ., Two new triterpenoid saponins from Sarcandra glabra. J.
Asian Nat Prod Res. (2005) Vol. 7(6):829-34.
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31(10):1529-1533.
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