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• Nghien ci>u - Ky thuat

Phan lap va thilt lap chat chuin cynarin

Nguyen Thi Anh Ngnyet', Phjm Phu-ong Chi' Nguyin Thi Duyen Anh', Pham Bong Phmmg'' 'Bo mdn Buoc lieu. Khoa Bvac. BH YDmrc Tp. Hd Chl Minh ' Trung ldm Bao loo vi NghiSn am phat Iriin ihiie nguin gdc Hr nhien BH YBimc Tp. Ho Chi Minh 'E-mail, [email protected] Summary

7:,t\T„7,,^ "^X^"'" t-"!'"^ Chmmakigraphy p/LC - column (71=40 cm. kl.) 600 q silica ael 10 04-0 063 mm) and Medium Piessure Uquk! Chromatography (MPLC) - column r 2 5 « 50 mkllwllh m'Tn^'rVn

Keywords: Cynann. Cynara caMunoulus. C. scolymus. refemnce standani. ISO Gwde 35. IS013528.

Aotisa (Cynara cardunculus L = C. scolymus L., Asteraceae ra) a mOt cay a w e bl4t aen 4 nhl4u nu'dc tr6n t h l giffl vi VlSt Nam do c i tac dgng thang m$t, W tiiu, 3ieu tri thieu nSng gan, mat, 14m giam cholesterol trong mau, trong aa, cynarin atrp'c coi nhu- la hoat chit chlnh " ^ i . HiSn nay trSn thj trcrang c6 rit nhiiu che pham t * actisO dOng ho trp- aiiu tn oSc bSnh v i gan mat va tieu hoa l ' " . wee tlSu chuin hba va loini nghl#m cynarin, add cloiogenic trong actls6 bing sac kl ldng hi^u nang cao (HPLC) c6 dd chpn Ipc cao aa va aang duvc nhiiu ni^ac sd dyng nhu'ng 6 ViSt Nam, viSc dinh lu'ong cynann trang la va cao actisS bing do p h i ti> ngoai (UV) '*J nSn cho k i t qua r i t khPng chlnh xac, vl phu'OTg phap nay cP ao chpn loc t h i p vi trong la actisp, ngpai cynarin cdn c6 cac aing phan cDa cynarin cUng vd'i r i t nhieu h(?p chit khac d i u cp cUng p h i UV v4i cynarin. Hon nCa, de dinh lupng cynarin can phai 06 chit chuin. Viae phan lap, thiet lap chat chuin a i i chiiu cynarin thay vl phai mua chat chuin tip nu'dc ngoai, aing thpi xay d^ng quy trtnii ainh Iirpng cynarin phgc vu chp viae kiem nghiSm ban thanh pham (cao chiet) va thanh phim ( c i actisp) la h i t siic can thiit.

061 tUCTlg v 4 p h m m g phap nghien c i i u Nguydn lt$u

La actisp tmji (200 kg) aupc thu hai tai phu*ng 12, Tp. oa Latvac thang 10/2014, n>a sach, a i rap

T*PCHiDU-glCHgC-7/2016(S6483NAM5«)

va njc be gan chlnh, lay riSng phin phiin la (90 kg) va xij II a l i n ajnh dype IISu.

Hoa c h i t - t h i l t bj

Hod chat: Con 96%, clorofpnr, ethyl acetat, benzen aat tiSu chuin phSn tloh (PA), acetonitnl (Merck), methanol (Merck), acid fbmiic (Merck), ethanol, acid Ibmilc ciJa Hang J. T Baker - M j ' Cynarin chuan (Phytolab - Diic, s616 2779).

Thiet bi

S i c kJ i6p mong (SKLM) du'pc thi,jc hiSn trSn ban ming silica gel F,^ trang sin (Merck). S i c kl opt Chan ktiPng (VLC) thup hiSn trSn cpt s i c kl (7>c40 cm). S i c k> long diiu che ap suit tnjng binh (I^PLC) Blorad (Bjoiogrc Duoflow Pathfinder 80 a i u d6 Quadtec UV- Vis). S i o ky long hiSu nang cao (HPLC) tien hanh trSn may Shimadzu LC-20A (Nhat), d i u dp PDA. P h i hpng ngpai (IR) dupc do tran may Nicolet iSSOO NIR-(TIR (Mf). cao phSp ao trSn duac thu'c hiSn tai Vian Klim nghiSm thuoc Tp. H P Chl Minh. Php cpng hu'dng tU- hat nhan (A/Mfi) dype ghi trSn may Bruker Avance 500 MHz; Php 'H-NMR duac ao p 500 MHz p h i

"C-NUR duac ao d 125 M H Z vdi TMS du'pc dCing iam chit chuin n i i (TMS) tai Vl$n Han iam Khpa hpc Wet Nam - Ha Npi. May do khoi p h i phan gBi cap Micrp QuattroAPI, ESCi Multi-mode ionization (I«icn3mass): May HPLC Wfeters 2695 Alliance aau dp PDA 2996, a i u dp M S / M S ; May dp p h i UV U-2010 (Shimadzu) - Trang tam Dao tao va NghlSn CU'U phat triin thuic nguin goc tv nhiSn BH Y DU'PC Tp. Ho Chl Minh.

(2)

• Nghien ciJu - Ky thuat

Phmmg phap nghien c i h j Chiit xuat vi phan l$p

Phien la tlfPl actisp aypc i n ajnh vi chiit ning vdi ccn 96% va sau dp la pen 48%. Djch chiit duac c6 thu hoi dung mdi de thu aypc cac long va l i e phan b6 lin lypt vdi clprpfbrm, ethyl acetat, n-butanol, thu hoi dung m6i a l ayoc cac cao chilt tyang yng. Cao /^butanol dyoc triin khai trSn s i c ky c6t chan kh6ng, chon phan doan giau cynarin a l phan lap tiip bing HPLC. K i t tinh lai trong dung m i l d i dype cynarin tinh khiit.

Tham dinh va thiit lip chit chuan cynarin phin l^p dugv

Xic Ifnh ciu tnic Php UV, MS va NMR.

Bd im: Xac dinh bang phypng phap DTA.

Binh tinh: bing SKLM (vdi 3 hS dung m6i khac nhau), HPLC, IR, MS va NMR.

Thd Unh khiit Bing HPLC-PDA va phyong phap quSt nhiet vi sal (DSC) o nhiSt dO tO 0 - 400 "C.

Xiy dung quy trinh dinh luang cynann bing HPLC: Khip sat diiu kien s i c kl, bao g i m : pha dpng, ttiOl gian phan tich, too dp dpng, byde sPng phat hiSn, nhiSt ap cpt 25 "C.

Thim dinh phuang phip dinh luang cynann bing HPLC: Thim ajnh quy trinh ajnh lypng cynann vdi cao chl tieu: tinh tyong thich hp thing, tinh aac hiSu, tinh tuyin tinh, ap lap lai va ap dUng.

Ddng 96; vidinh gii Of ddng nhat ig trong qui trinh ddng gdi

Cynarin ayoc dpng gpi vap Ip thuy tinh mau nau, c6 Idp asm tellpn va hSn kin trong Glpve- Bpx c h i a khi nito, m l i i n g 10 mg, apng thanh 45 Ip a l aanh gia aing nhit 16 trang qua trinh ding g6i. Danh gia kit qua thep ISO Guide 351". c h i t chuin phan lap aypc adng gdi tai ViSn Kilm nghiSm Thuic TP H i Chl Minh trcng a i l u kiSn adng gdi tieu chuin.

xac i»n/7 gii tri in O/nh, tfp khdng dim bio do theo ISO 1352a "i vi gii trj cdng b6 trin phiiu kiim ngh/^m dya tren kit qui djnh luvng t^l 2 phdng thl nghiem

Kit qua ajnh lypng aypc thyc hipn tgi It nhit 2 phdng thl nghiSm ape ISp aat chuin GLR hoac ISO 17025, trong ap cP It nhit mpt phdng thl nghipm cd au thim quyin va y nghTa phap ly a i i vdi Vipt Nam, n^i phdng se aypc g i i 6 ip ngiu nhidn kdm thep chit chuin, quy trinh phan tich. Hai phPng thi nghiSm tham gia aanh gia chit chuin gim- Khpa Thilt tap chit chuin va chit a l l chieu, Khpa Kilm

nghipm vat Ij dp lypng - Vien Kiem nghiSm Thuic TP Hd Chl Minh.

K§t qua nghien cuu

C h i l t x u i t va phan lap cynarin tit' l i actisi Chiet xuat

lit 200 kg la tool, noc bo gan phlnh thu duoc 90 kg phien la typi actisd. Tiln hanh i n dinh li chilt vdi 80 lit cin 96% d nhipt dp 60°C trong 15 phut, ep, ipc lay dich c h i l t B3 cdn lai duoc chilt lan 2 tyong ty nhy trdn vdi 90 lit con 48%. Todn bp dich dp cdn dype cd thu hoi dung mdi dydi ap suit giam thu dype 9 kg cao ldng actisp (ALE).

Phan tach cic phin do^n giiu cynarin bing phuong phip phintrn Idng-ldng

9 kg cao Idng dype lie phdn b i lln lypt vdi clpralbnn, ethyl acetat, rj-butanol, thu hii dung mdi d l thu dyoc cac cao typng dng, bao gim: cao chloroform (150 g), cap ethyl acetat (90 g) vd cao n-butanoi (200 g). Cao n-butanol auoc dCing tdch phan doan giau cynarin trdn s i c kf c i t chdn khdng

Phin tich phan doan giiu cynarin bang sic kf cgt chin khdng (VLC)

100 g cap n-butanol (dp i m 25%) dyoc tnln khai trdn s i c k^ cpt chan khdng vdi cdt 7 '< 40 cm, khii lypng 600 g silica gel 0,04-0,063 mm, pha apng ethyl acetat va ethyl acetat-methanol vdi loong methanol tSng d i n . Klim tra cac phdn doan trdn s i c k!? Idp mdng, gom cao phan dogn cp thdnh phin gidng nhau. K i t qua thu dyoc 9 phan doan, trong ap, phan aogn 9 cp ti Id vet cynarin cao vd It tap (hlnh 1). Tiln hanh lap lai cpt VLC vdi cCing aiiu kien nhy tren thu dype t i n g odng 32 g phSn doan 9 va ayoc sy dung a l phan lap cynarin.

Phin l$p cynarin bang sac kf ldng ip suit trung binh (MPLC)

Triin khai phan aoan 9 (1 g x 24 lin) tren hS thing may MPLC, cpt s i c kJ 2,5 « SO cm, 170 g silica gel RP18 (0,04 « 0,063 mm), pha apng gim acetpnitril (dung mPi B) va acid fdmiic 0,1% (dung mPi A) vdi chypng trinh gradient nhy sau: 8% B (4 phdt), 8 - 15 % B (70 phut), 15 % B (30 phiit), 15 - 30 % B (90 phdt), 30 % B (30 phdt), 30 - 100 % B (15 phut), t i c dp ddng 10 ml/phdt, thl tich hdng 20 ml va byde sdng phdt hien 323 nm.

K i t qua cho thiy cd 3 phdn doan chlnh (hlnh 2), trong ap phan apan 3 aypc klim tra tien HPLC- PDA cd thdi gian lyu vd p h i UV trung vdi cynarin chuin, gpp t i t c i cac phan apan nay cua 24 cpt, cP thu h l l dung mdi, iam lanh, xuit hidn tda, Ipc tua dydi dp suit gidm thu dype 460 mg bdt vd ainh hlnh mau tring.

T*PCHl Dirpc HQC - 7/2016 (S6 483 NAM M)

(3)

• Nghien CIPU - Ky thuat

H i n h 1 : Kit qud phdn Idp trdn 0t VLC Cy: cynarin chuin Binh tinh va xac djnh c l u true Ph6 UV-Vis: Ph6 UVcua cynarin c6 3 dinh hap thu cyx; 6^\ tai 216,7; 243,8 vd 322 nm.

H i n h 3: Phi UV-Vis cOa cynarin phdn l$p

H i n h 4 : PhS IR cQa cynarin phdn Idp Pho NMR: DO Ii0u p h f i ' W vS " C - W M / ? c u a c y n a n n p h f l n l$p t r o n g b a n g 1 p h u h(?p v6\ dO" li^u p h o NMR cOa c y n a r i n t h e o tSi ii$u P'

B i n g 1 : So sdnh dOliduphi * H - WW/? fCD30D, 500 MHz; i/^ "C - «MR c£Ja cynarin phdn Idp v(n phi

cynann theo tdi li$u CynarbiphSnl^

(CD,OD,SO0MH:^

Cynann fscjrf J, Wf-O-csfeoyftTu/njcJ

2 33,0f ^33-2j1ni(ZI 32,9 f 1,B3-2.87/nl2Hl 3 73.0(1 5.39ni{1H) 73,Qrf 5.36m(1H) 4 75,3tf 3,65<tf(1H,9,S;3,5Hz) 7S.3tf 3,61dd(1H.9.6:39.6H?l

TAP CHt DlfQC HQC - 7/2016 ( S 6 483 N A M 56)

H i n h 2 : K e f q u a phdn Idp trdn c6t MPLC

Pho IR: P h f i IR c u a c y n a n n d i ^ u c h e c h o c ^ c dfnh h a p t h u 6dc tru'ng c u a - O H ( 3 3 9 6 cm^), c a r b o n y l c u a - C O O H ( 1 7 1 6 cm-^). chi>c ester cartxsnyl ( 1 6 8 3 cm-^), v b n g b e n z e n ( 1 5 3 3 , 8 1 4 cm^) ( x e m h i n h 4 ) .

Pho MS: P h 6 k h 6 i ESf-MS (negative) cOa C S - B 5 c h o m a n h nvi = 5 1 5 , 1 4 t u o ' n g i>ng v&i m a n h i o n p h S n tu- [ M - H f p h u hp'p v * i c f i n g t h i i c n g u y § n C j ^ H ^ O , , Id c 6 n g thii-c n g u y S n c u a c y n a r i n ( h i n h 5 ) .

fete

Ts.Jll>->,.

H i n h S: Phi MS cua cynann phin lip CyiaikiiiliAii$p

(CDfiD,miim

Cynarin (add 1,3.di-0.aifeoylqiMt;j

(ixi,oD,miim'i

5 67,8i) ™ ' ' * ' l ' " ' ' " • « ! " « 87,t^ « i f l l ( 1 H , ) 1 , ! , 9 , 6 ;

. . . 83-2,87ill(2Hl 6 41,31 l.a6-2.5SmP

7 174,6 i

f 127,4s 174,es

127,4s 2 116,U 6J4ill[1H, 21IHZ1 m 4 r f ~ ~ «

146,5s i,81l((1H,2,0H;l

149,38

y 116,611 6ail(lH.8,5Hz) 11B1J sr«„f,u ,^^pr—

e 122,0116,61 l > l l l H , 8 a 2 . 0 t e | m n j « . « ^ ( . u . ; • ' . , n m - 7- 147,U 7,49llllH.16.0Ha 1477,1 7 4 « ; ( i i i , . p H r l 6' l I M i l 6.10il(1H,ie,0H;l l i s i r f 6,11 Ji1H.159H7l '

(4)

• Nghien ciJu - Ky thuat

Cynarin p h a n ^

S^

ff 167,8 s 1' 1Z7.5S r 115,5 d 3" 146,7 s 4" 149,6 s 5* 116,6 d

5„

6,95d(1H, 1.5 Hz)

6.66d{1H,fi,0Hz)

CyTiarin facid f>(frO«afep)'ft;tHnic;

S^

167,8 S 127,5 s 115,5 d 146,7 s 149,7 s 116,6 d 6* 122,9d6.77(W(1H,8,0;1,5Hz) 123,0d r 147,7 d

8" 1152 d 9" 168,9 s

7,51d(1H,16,0Hz}

621d(1H.16.0Hz) 147,8 d 115,1 d 168,9 s

<S„

6,92d(1H,2,0Hz)

6,63d(lH,e,2Hz) 574(W(1H,8,2;2,0Hz}

7.48 d(1H, 15,9 Hz) 6,ied(1H.15,9Hz)

Hinh 6: Cau tnic phdn ttr cOar^arin Xac djnh tap chit lien quan Dinh tinh bing sic k^ I6p mdng Thi/c hi6n v&i 3 h# dung mdi l^h^c nhau cfi tJO phan CLPC tSng dan cho Hi^iy cynarin phSn i^p cM cho mOt vet duy nh^t trSn s i c 1^ do (hlnh 7).

UV2S4nm TTFeCI,

Hinh 7: Sic ky dd cynann vdi 3 hd dung mdi khdc nhau Chu ^fch:TP-cao n-butanol Actisd: C: cynarin i^uin; T cynann phdn l$p

Cdc h$ dung mdi sdc kj': (1): Benzen - aceton - acid tannic (3:3:0,5) (2): eth^ acetat - nu6c - acid fonnic (8:0,5:0,5) (3): ethyl acetat - methanol - nu^ - acid fonnic (13:1:1:0,5) Ojnh tinh bing HPLC- PDA tinh theo % di^n tich pic \d 1,76 %.

Ham luxyng tgp c6 trong cynann dieu che

Hinh 8: Sic ky 66 HPLC kiim tra dd tinh khiit cOa chit phin l$p dut?c

T ^ CHi D i r o c HQC - 7/2016 ( S 6 483 N A M 56)

(5)

^Jjghien ciru - Ky thuat

Phuang phap qudt nhl^vi sai (DSC)\

Cynarin phan lap ep ap tinh khiet g7,67% a6i vdi phypng phap quet nhiet vi sai.

Hlnh 9: /VftipK^ DSC Clia mJo cynarin diiu chi T h i m dinh quy trinh djnh l u v n g Oieu kidn sac kf

cpt Sunfire CIS (4,6 » 250 mm, 5 pm); pha apng la acetpnitril-aeid fbmiic 0,1% (17 83)' thdl gian phan tich 15 phut, t6e ap ddng 1 ml/phut bodosPng phat hipn 323 nm; nhiet dp cpt 25 "c' the tieh tiem m i u 10 pl; mSu thy va cynann chulii dype hda tan trong methanci d npng dp 100 ppm (0,1 mg/ml). Ham lypng cynarin phan Bp dooo xac ainh bing each so sanh vdi dien tich dinh eua cynarin ehuin.

77i^m dinh quy trinh djnh lufng Quy trinh dinh l y p n g bang HPLC-PDA dS thiet lap dat cac yeu cau sau aay;

Bdt tinh tuang thich hi thdng (RSD% cua thdi gian lyu t, va dien tieh dinh S < 2%, k' 2 1 0" 1 05 s a s 2 , 0 ; 0 , S s A s £ 1 , 5 ; R s > 1 , 5 ) ' ' '

Bat tinh die hidu (t^ eua cynarin phan lap la 10,5 phiit va phS UVcua m i u thi> hoan tppn triing khdp vdi cynarin chuin)

Khoing tuyin tinh cua cynann la 2,5-750 pg/mi.

Bd * ; ? / ep RSD = 0,71 % va do dUng cp ti le phuc hPi ty 102,5-104,0%.

0 6 r g goi va aanh gia ddng n h i t Ip Bdng gdi: Kh6i lypng ban 3au. 450 mg KhSi lypng dPng gpi-10 mg/1 lp Ting s l Ip: 44 Ip

Btnh gii adng nhat Ig: S l lp aanh gia;

g = V « + 1 = 7 Ip.

Liy ngSu nhien 7 Ip bing phin mem Excel, s l thd ty cac Ipse Ily ae ainh lypng la. 2.4 7 11 15 20,30. M i l Ip ainh lypng 2 lln. K i t qua ainh lylinq dyoc trtnh bay d bang 2.

Bang 2: Kk qui dinh luang cynann dinh gii dina nhitid

stt Losi^ LinlKI U „ ; | % | TmnrilMna' ' " " •••-4 i4.43 94,69

T * P C H l D U p C HQC - 7/2016 ( S 6 4(0 N A M S<5"

94,28 94 j e

20 93,70

94,22 93,75 Danh gia a i n g nhat giya cac lp theo ISO Guide 35 nhy sau;

Bang 3: Phin tich phuang sai mqtyiu Id Iheo ANOVA

/l//lSnx«.F„ = 1,412 < F,^ = 3,866 vi J - 0,213 > „ „ - 0,073

^ Dp ap ap dung cong thdc chuyin d l i d l tinh Ket qua thu dype nhy sau;

HSanvmg -MSwilMn

;; = 0,0027;^ « « = 0,1169 = >

«» = = 0,0137; j > i = 0,8607 Nhin xit ^^^"""is - MSwIhin

Nhin Hit Chung: cae Ip cynarin aing nhit tronq

«

qua trinh apng gpl.

Banh gia c h i t c l i u i n lien phdng thl nghidm Bingi:Kilquidinhluangcynannlaihalpbdngthlnghi$m

93,66

94,45 94,26

94,69

94,37 94,72 94,14

94,06

94,07

Trung binh 94,20 94,44

94,33 P^l: Khoa T}iiill$p chit chuin-dlit dii diliu Yi^kiim

nghl^BluSc-iPHoCNMlnti

Pm2:Klm VH if do lmmg. Vifn KKm n^ijm mic TPH6 aiiUinh

Bang 5: Kit qui dinh gii liin phdng thl nghiim theo ANOVA

phmm fto bws Ixnh GlOa cac nhan 0,D52(O8 Tronq Kmiinton 0,890863 Tflng tftw 0.942892

0,052008 0.563784 4.964603

Nhin xit: F„ = 0,584 < F, = 4,065. Do ap kit qua tnrng binh ciJa 2 phpng thl nghiem khac nhau Khdng eP nghta, phyong phap phan tich c6 ap IJp lai cap, ham lyong cynarin aiiu ehl ayoc khPng phu thuPc vao phdng thl nghipm tham gia aanh gia

(6)

• Nghien CLFU - Ky thuat

X^c dfnh gia tri an dinh, do Ichdng dam tiao do va gia tri cong bd tT%n phidu l i i l m nghi|m cua cynarin

B i n g 6 : Kit qua tinh gia trj in ffinh ham luong cynarin

5=),5xs' X--S

! • • ! Tnmgbkih KUchs idindi s ' m o i

x*.

94^7 0^93 9 4 ^ 0,222

I - , 0,334 93.89 94,55 94,26 0,213 94,26 0,242

x-, 0,362 93,90 94,62 94.26 0,211 9 4 ^ 0240

I " , 0,359 93,90 94,62 9 4 i 6 0211 94,26 0239

X", 0,358 93,90 94,62 94,26 0210 94,26 0,239 Nh$n xdt S a u 4 l ^ n t h a y d o i , s * = 0 , 2 3 9 Ithong doi, X* = 9 4 , 2 6 % d u v c c ^ g n .

Tt> k i t q u a t i n h t h e o z - s c o r e , t a t c a g i a frj d e u c 6 \z\ < 2. T i n h kei q u a g i a trj a n fflnh t r e n 1 2 Itet q u a n h i / s a u .

- H a m l i n i n g t r u n g b i n h : 9 4 , 2 6 % - € ) O I § c h s : 0 , 2 1 0 - eo khflng dam bao do ^i. 0.086.

Nhdnxdtchung: Ham lugng cynarin la 94,26 % tinh trfin c h l pheim nguyfin trgng, d0 khflng dam bao do = 0,086; dfl Ifidi = 0.210 (n = 12).

Kdt luan

Tif 200 kg ta act'sd tuo'i (Cynara scolymus L.) da chilt xuit va phan lap du^c 450 mg cynarin d l si> dgng iam chit chuin doi chilu. Chit t ^ u l n cynarin phSn lap du^c tham dmh d i y du cac

tifiu chl o j a chit chuan theo h u ^ g d i n ciia ISO 13528 va ISO 35. Ket qua cho thay qrnarin phSn lap dat ti&u chuin qudc gia (secondary standard}

vffi ham lup'ng dup'c xac ^ n h la 94,26% tinh theo nguyfin trgng (n = 12; s = 0,21; fi = 0,086). Chit diuan cynarin da phSn l|p va thilt l$p cfl the 6\Kfc Crng dung cho cflng vi#c kilm nghi6m diat iuvng nguyfin lifiu, cao ban ftanh pham vd thanh phim Kf actiso. DSy la lln d i u tifin vific phSn lap va thilt lap chit chuan d l i chieu cynarin duffc bao cao trong nufl'c.

Tai iieu t h a m khdo 1. Worid Health Organization (WHO) (2009), Monographs o n selected Medidnal plants, volume 4^

folium cynarae, pp. 92-107.

2 . Ng5 Van Thu, T r l n Hung p 0 1 1 ) , D u p c mu hQc NXB Y h o c , tr 405-409.

3. Xianfeng Z h u el a/. (2009). T h r e e di-0- caffeoylquinic a d d derivatives from the heads of Cynara scolymus L". Natural Product Research. 23 (6) pp 527- 532.

4 . Lattanzio v., Paul A. K., Linsalata V , CardinaliA, (2009), "Globe artidioke: Afunctional food and source of nutraceutical ingredients'. Joumal of Functional Food I 131-144.

5. BO Y t6 (2009), D u p c ^Sn Vidt Nam IV. NhS XuSt ban Y hgc HA N^i, tr. 681-682.

6. ISO Guide 35 (2006), Reference materiais - General and statistical principles for certification, ISO.

7. ISO 13528 (2005), Stafistical methods for use in proficiency testing by interiaboratory comparisons. ISO.

{Ngdy nhdn bdi: 17/05/2016 - Ngdy duydt dSng: 05/07/2016)

Tac dung Idiang Idiuan va ch6ng oxy lioa cua re cay sim (Rhodomyrtus tomentosa (Ait.) Hassli.)

Nguyen Dinh Dung '*, Trieu Duy Di^t' ' Vien yhoc Phong xa va U budu Qudn dgi 'Tning Idm Bdo lgo va Nghien cihr Diruc Qudn dgi. Hgc vien Qudiiy ' E-mail: [email protected]

Summary

c e i e u s S ^ J S i S ' f . f ' * ° * S ! ^ ^ tomentosa (Ait) Hassk. was experimenlaily estimated an Bacilus S S S ^ s K ^ r " ^ ^ ' " ' ' ^ ? * ^ " ' " ' ' ™ ^ Bsciltuspumiius^eieby MIC v^s achieved at the T l T ^ ' ± u S ! ^ i ^ ^ ^ T f ^ "'^^'^simultaneously. MydiemotextmctsatconceSidl S r O O ^ a e S I S . " ^ ^ " ^ ' ^ ^ " ' ^ " P to50%, equivaleiiltaasccvbk^acklatcancentialicn

Keywonfc/Rtatomyrtus tomentosa r/tt; Hassk., anStacteratanSoxte/it

T,^P CHi D i r p c HQC - 7/2016 ( S 6 483 N A M » )

Referensi

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