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y Nghien ciru - Ky thuat

chinh trong bai thulc. Djch chilt nu-ac cua kim n g i n d i n g co t i e dyng cai thien tinh trgng hen dj J i g do long trang tn>ng gay ra, i>c e h l hoat hoa t l bao mast do trypsin. Kim ngan d i n g thWng duwe dung trong chi>a tri cac bpnh man ngiJa.

may day, ban sai va eac benh di ling khic. Niic nac CO tac dyng chlng dj u-ng, lam t i n g su'c d l khang cua ca t h l . che pham tCF nuc nac du^c si>

dung de dilu tri bpnh vay n l n . m l day ra. Hoang ba thuwig du^e si> dung d l dieu trf c i c (^i>ng benh benh ngi>a, phii n l v i la m6t trong nam vi thulc thu-o-ng dygc SLF dyng dieu tri eczema o- Trung Quic f i .

Ket l u | n

Cao EZ-Hp v i EZ-EtOH a ca 2 lieu thi> (tuong duOTig v6i 14,4 g DL/kg va 43.2 g DL/kg) co t i c dyng chraig soc tren chupt nhit tring * mo hinh giy s i c bang compound 48/80.

Cao EZ-Hp v i EZ-EtOH a ca 2 lieu thij (tuwng du-ang v&i 14.4 g DUkg v i 43,2 g DLftg) co t i c dyng chong ngi>a trin chupt nhit fring a m6 hinh g i y ngiJa bing compound 48/80.

Tai lieu tham khao 1. Nguygn Mgnh Tuyen. PhCrng H6a Binh, Le Thi Minh v i OS. (2015). "Danh gia tac dyng chlng vi§m

thyc nghifm cOa cao d|c bao chi tiP djch chilt ethanol bai thuSc EZ". T?p chi Du%rc hpc, s6 7, 6-10.

2. Nguy^ Mgnh Tuyln. Phiing Hoa Binh, L§ Thj Minh v i CS. (2015), 'Oanh g i i t i c dyng chlng viem ttiyc nghi#m ciia cao d|c bio rfil tCr djch chilt nir&c bat thufic EZ", T^ip <^iDtfqc hoc. s l 10, 50-54.

3. Chandrashekhar V. M.. Halagali KS., Nidavani R.

B. (2011), "Anti-allergic activity of Gennan chamomile {Matricaria recutita L.) in mast cell mediated altefgy made]', J. Ethnophannacol. 137(1): 336-40.

4. H R Chitme. Mallikarjun Malipatil, V M Chandrashekhar and P M Prashant (2010). Antiallergic activity of Anstolot^i bracteolata Lank In animal model Indian Joumal of Experimental BMogy. Vol 48,46-52.

5. Jin-IWii Y. et al (2000). *lxeris dentata green sap inhibits both compound 48/80-induced anaphylaxis- like response and IgE-mediated anaphylactic response in munne model. Bioi Pharm. Bull, 25 (1). 5-9.

6. Wedemeyer J.. Tsai M., Glli S. J. (2000), "Roles of mast cells and basophils in innate and accquire immunity", Cun. Opin. Immunol., 12(6). 624-31

J- >^'an Y, F, Mao Q. Q.. |p s P, Lin Z. X.. Che C. T.

(2011), "Comparison on the anti-inflammatory effect of Cortex phellodendri Chlner^sis and Cortexpheliodendri Amurensis in 12-0-tetradecanoyl-phorbol-13-acetate- ' I " 3 7 ( 3 M I I 5 - 1 ™ ™ ' " " ' " • • •'• ^ " ' " ' " " " • ™ » » ' .

„ . . , ° ; , ° ' ^^''-''' f,"^^'' " ' " ' " 9 <^y Ihuic va vi lliuic Vi^t Nam, Nha xuat ban Y hpc. Hi Nil, 75-79 197- 199, 204-205, 298-300, 394-296 726-728 (Wgay nhan bii: 03/06/2016 - Ngiy duyit ding: 01/09/201S)

Nghien cmi xay dung tieu chuin chSt Iwcmg ciia du-o-c lieu tao meo (Fmctus Docyniae indicae)

Hoang Vi|t Dung'", Nguyin VSn B^ch', Pbam Birc Thjnh' Nguyin Hoing Hifp", Hoang Quynh Hoa' 'Hpc vipn Quany

^TrudmgBpihpcBirpcHaNpi 'E-mail: vietdungk85<^yahoa.com

some qualifk^non criteria for S ' o S w ^ ^ c S T S ™ , ^ T * ^ f ^ ^"^ chamcterized by ashes, heavymetals, cnmMeJo Descnptxm. identifk:ation, tes on drying, quantHtatkm, total

Keywords: Docynia inOca, standaidizatkm.

^^^•T.. * ° f " " • ' " ^ ' ^ "^" ° " " i ^ " * " vClng rail phia _ u Viet Nam, pua cua hai Ici4l dy tio mto vi Bac thi ciy chua chat (Malus doumeri Bors A S L f f l ^ " ^ " ^ "^ * * " ' ISn trong 9pl ten Chev.) lai phan b6 kha han c h i . VI v j y trong thu^

a,ng nht, trong si dgng lam Ihu6c chua banh i « . t4, dugc l«u thutmg a , ^ nhan dan t a T » H ! ^ Trong kh, cay tao mec (Doc,.,a indk. pfl,all.) lam thu6c la qua L Ty tao m l ^uy h h ™

T * ' CHf D i r p c HQC - m 0 1 6 (SO 485 NAM 56?

(2)

Nghien CU'U-Ky thuat

trong D u w e d i e n V i $ t N a m ( D D V N ) IV k h o n g c o c h u y g n l u i n v ^ du'crc li§u t i o m e o ; m i chf c o c h u y e n l u a n v e s o n tra ( q u a c h i n 6a t h a i p h i l n , p h o i h a y s a y k h 6 c u a c a y c h u a e h i t ) PI. D o d o . v i e c nghien a > u x a y d y n g t i e u c h u i n chat i u ^ n g d u t ^ c lieu t i o m e o l i viSc l a m c a n t h i ^ t n h a m g o p p h l n kiem soat, k i e m n g h i S m c h i t l u w n g c u a loai d u ^ c lieu k h i p h o b i e n nay.

N g u y e n l i e u v a phu>tyng p h a p Nguyen lieu

Qua t i o m i o du-ac thu h i i tgi huy$n Mu Cang Chii, tinh Yen B i i (mau TM1); thu hii tgi huyen Bac Yin, tfnh Sen La (mau TM2); &iu h i i tgi huy$n Sa Pa, tinh Lao Cai (mlu TIV13) vao thing 10/2015 Sau dd, qua t i o meo du^c n>a sach, thii lat v i say Idle 6- 70°C den him I m thich hp'p.

Hoa c h i t , dung moi

- C h a t c h u a n q u e r c e t i n , h i m i u ^ n g 9 8 % ( h a n g Sigma); A c i d h y d r o d o r i c d g m d i e , natri h y d r o x y d , sat (III) ciorid, a m o n i a c d i m d a c : d g t t i e u c h u a r i tinh k h i i t h o a hgc ( T n j n g Q u 6 c ) .

- IVlethanol, n-butanol, ethanol- dgt tieu chuan tinh khiit phin tieh (Trung Qu6c); Acetonitnl, acid formic: dgt tieu chuan dung cho HPLC (Merck).

Thilt bj

- H# t h i n g H P L C W a t e r s 2 6 9 5 D ; D e t e c t o r P D A 2998; c o t S u n f i r e R P - 1 8 ( 2 5 0 x 4 , 6 m m , 5 u m

100A°). ' - B l lac s i e u i m E l m a s o n i c .

- C a n p h a n t i e h Mettler d 6 c h f n h x a c 0,1 m q

ThyyST. ^ - TCi s a y m e m m e r t (Bt>c).

- Bp Ipc hut Chan khong AlHech - My.

Phwyng phap nghien cihj Mota

M 6 ta b i n g c a m q u a n . Ofnh tinh Phin ung hoa hgc

l-iy khoang 2 g bpt du-gc li§u, them 10 ml ethanol 90% (TT). Dun sol trong 3-5 phut, d l ngupi.

lpc. Lay 2 ml djch lpc pha loang vai 10 ml ethanol 90 % (TT) r l i chia v i o 3 Ing nghiSm:

Ong 1: Them 5 gipt acid hydrodoric dim dac (TT) v i it bpt magnesi.

6ng 2: Thim 2 gipt dung djch natri hydroxyd 20 % (TT). ' '

Ong 3: Thim 2 gipt dung djch s i t (III) dorid 5%(TT).

Sic ky Idp mong (Phy lye 5.4, DDVN IV) B i n m6ng silica gel 60 F

T ^ CHi DUOC HQC - 9/2016 (SO 485 NAM 56)

Dung moi khai trien: n-Butanol: nu-oc (10:1).

Dung dieh tfiu-: dun h6i lu\i 5 g bpt du^c lieu vai 30 ml e&ianol 96 % (TT) trong 10 phiit. Lpc. Djch Ipc duvc e6 den c i n . Phin tan d n vo-i 10 ml nirac sau dd lac vai 10 ml ethyl acetat (TT) 2 lan, dieh ethyl acetat duwe bay hai con khoang 1 ml dung l i m dung djch thu".

Cich t i l n hanh: cham len ban mong 10 pi dung djch thi>. Sau khi triln khai, d l kho ban mong ngoii khong khi a nhipt dp phdng sau do hiin mau bang hai amoniac.

Dinh gia: Xac djnh g i i trj R, x 100 cua c i e v l t xuit hiSn tren sic k^ 66.

Bgim

T i e n h a n h t h e o phuiD-ng p h a p x a e d i n h m i t k h o i lu'p'ng d o l a m k h o ( P h y lye 9.6, D D V N IV).

Djnh luvng

T i e n h i n h d j n h lu'p'ng quereetin b a n g p h u ' a n g p h a p s i c ky l o n g h i i u n a n g c a o ( P h y l u c 5 3 D D V N IV).

Diiu ki$n sic ky: C p t S u n f i r e s R P - C 1 8 (5 p m , 1 0 0 A " , 2 5 0 X 4 , 6 m m ) h o a c fij'ang d u ' a n g ; Bu'O'c s d n g p h a t h i p n : 3 6 4 n m ; T i e d p d d n g : 1 ml/phQt;

The t f c h Bern: 2 0 m l , Nhifit d p edt: 2 8 " C ; P h a d p n g : c h u o - n g t r i n h g r a d i e n t c u a p h a dOng nhu- d b a n g 1 .

^Bn^V.Chuung trinh gradient c6a pha d^ng

(pfiOQ 0 10 11 20 21 30

TyledungmmACN

(%)

35 35 100 100 35 35

Ty 1$ dung m& dung djch acid fbrmic 0,1% (%)

65 65 0 0 66 65 Chuan bi miu thu- va miu chuin - C h u i n bj d u n g d j d i thCc:

C i n c h f n h x a c k h o a n g 5 , 0 0 0 g b p t d u ^ e l i i u , c h o v a o b i n h n 6 n d u n g tich 1 0 0 m l . T h e m k h o a n g 2 5 m l d u n g m o i M e O H , lac s i 6 u i m t r o n g t h a i g i a n 6 0 p h i i t if 5 0 ° C ( l a m l#p Igj 4 l a n ) . G p p c i c d j c h c h i l t v i o b i n h d j n h mi>c 1 0 0 m l , t h S m d u n g m o i c h i e t vfFa d u d i n v g c h , l i e d e u . D u n g d j c h t r o n g b i n h du'p'c Ipc q u a m a n g 0 , 4 5 p m v i d u ' a c t i i m v a o h i t h o n g p h a n t i c h H P L C .

- C h u i n bl d u n g d j c h c h u i n :

C a n e h f n h x a c m p t lu'p'ng c h i t c h u a n quereetin s a u d d h o a t a n v a p h a l o a n g v a i m e t h a n o l d l dunyc d u n g d j c h c h u i n l a m vi?e c 6 n i n g 6b k h o i n q fi>

2 , 0 p g / m l . Cich sin hanh

Tiim lan lu'p't dung djch thtr v i dung djch d i u i n v i o he thing sic ky. Tien hinh sic k^ theo dilu

(3)

' Nghien CLFU - Ky thuat

i^an da neu, ghi thai gian lim va dl$n tich cOa pic quereetin cua tCmg dung djch.

Tinh kit qua

Ham lirang quercetin (%. kl/kl) trong qua tao meo kho tuyet dot duwc tinh theo c6ng thiJc:

Sa.xm„x(100-h) HL% =

C^ =< So, X too X 10-* X 100 X 100 Trong do:

- Cg^ Nong 0 dimg djch chuan ([igini).

- S^ S,^: Dien tich pic quercelm frwig dung dicnUiilva dung (Uch chuan (iiV^s).

-m; Kha lupng duoc b^i^mi^ lupng (gj.

-kSaimcOa dupc liSii (%).

Tro toin phan

Tlin hanh theo phu'ang phap xac dinh tro toan phan, Phy Igc 9.8. DDVN iV.

Kim log! ning

Lay 1,0 g che phim, tien hanh theo phuong phap 3, Phg luc 9.4.8. DBVN IV. DiJng 1,0 ml dung djch chi mau 10 phan trieu (TT) de chuSn bi m i u doi chieu.

Tyl^vgnnit

Ti4n hanh xac dinh phin bOt vgn nat va minh vo c6 du<>ng kinh nho ho'n 1,0 cm theo phuang phap xac dinh tf le vun nat Irong duoc lieu Phu Igc 12.12, DDVN IV. . . V

Ket qua va ban luan M6ta

_ Qua quan sat va mb ta, d i nghi di^a ra dac diem nhan dang ciJa duvc lieu tao mac g6m- qua thit hlnh ciu del, da thai phlin ngang day khoang 0,2 cm d i n 0,5 cm, dud'ng kinh khoang 1 5 cm

den 3,0 cm. V6 ngoai mau nSu s i m , nhan nheo.

Thit qua mem. hoi hing, glOa co 5 hach ciing, m i l hach chiia 3-7 hat. Hat mau nau, dai 0,6-0,8 cm, dud'ng kinh 0,3-0,4 cm. Thjt quS c i v| chua, chat, hoi ngpt.

Djnh tinh Phan img hia hgc

^ Ket qua djnh tinh 3 m i u duvc li$u tao mdo bang phan ling hoa hpc d i u cho k i t qua nhu- 4 bing 2.

Bang 2; Phin ung hoa hoc dlnh tinh duvc ii$utaomeo TT Thu6cthir

1 HCIdgmagc^Mg 2 NaOH 20%

3 Feci, 5%

Xuat hign mau llm 36 Xult liign mau v^na d§m Xult liign mau nau tim

l^nthH iaumi(g) BiSmKi

Bang 3: Dp JmciJa dupc liiu tao meo MSuTt^2

K i t qua bang 2 chung to trong duvc ll#u tao meo cd chua nhom hop chit flavonoid va cd t h i sil dgng 3 phan ling Irong bang nay d i d|nh tinh thanh phin hda hpc trong duvc ll$u tao mdo.

Sic ky lap mong

Sau khi khai tnen sac ky va hiSn mau bing hoi amoniac dam dac, tr§n ban mdng sic k j ciia 3 m i u dich chiit duvc ll$u deu thay xuat hipn rd 02 vet mau vang nau cd h5 sd djch chuyen R, x 100 lan lupt la khpang 29-30 va khoang 72-73. K i t q u i nay oho thay hp dung mdi n-butanoi:nu*; (10:1) phli hpp de khai triin sac tcj Idp mdng m i u djch chiit tap mao.

K i t q u i xac dlnh dp am cOa 3 mau duvc li$u du'pc trinh bay d bang 3.

B^im(%) Mlu Tim M B6iinl%l

Nhu vjy, dp i m cua 3 m i u dupc liSu khoang 8,96-10,29%. Du'a tren k i t qua th^fc t i va chuyen luan son tra trang DDVN IV, d« nghj dua ra gidi han dp am ciia dupc li$u tao mao la khdng qua 13,0%.

Djnh Ivpng

K i t q u i xac dinh hSm lupng quercetin trong 3 m i u dupc ii#u dupc trinh bay it b i n g 4.

T*P CHi DirglC HQC - 9/2016 (S(i 485 N A M S 7

(4)

• Nghien cu'u - Ky thuat

Bang 4 : Kit qua dinh luang quercetin trong (Aflpc lieu iao meo Lanfhv

1 2 3 4 5

Trung blr«)±SD(%) RSD (%}

Uwmi{g) 5,0021 5,0016 5,0009 5,0011 5.0003 5,0008

Hamlugng(pKn:^(!Q 0,0042S 0,00417 0,00433 0,00447 0,00438 0,00445 0,00434 + 0,00011

2,57

Maum2('g) 5,0004 5,0009 5,0015 5,0011 5,0006 5,0017

Hamlumg(pienx6n(%) lliuTII3(gl 0,00534

0,00555 0,00518 0,00522 0,00526 0,00538 0,00532 + 0,00013

2,52

5,0010 4,9998 5.0021 5,M12 5,0003 5,0008

0,00511 0,00503 0,00488 0.00502 0,00496 0,00481 0,00497±0,00011

2,20 K e t q u i b a n g 4 e h o t h a y h i m lu'p'ng q u e r c e t i n

b'ong 3 m l u q u a t a o m e o k h o a n g 0 , 0 0 4 3 4 - 0 , 0 0 5 3 2 % t f n h t h e o d u ' p c l i e u k h o kiet. D y a trSn k4t qua thyc t i , de nghj du'a ra giffi hgn ham lu'png quercetin trong du-pc lieu t i o m i o

Bang 5: 7 y / e f r o toan phin cua dupc lieu tao meo i i khong it hen 0,0030%.

Tro toan phan

Ket q u i xac ^ n h tro toin phln cua 3 m l u du^e lieu du'p'c trinh tray d bang 5.

UtnOiv Miu mi (c T9l9(%) Tyl^m MiuTm(g)

2,9995

TiungbinhtSD(%) RSD(%)

Ket qua bing 5 cho thiy ty l i tro t o i n phan trong 3 m l u du'pc iiiu nam trong khoing 6,83- 7,55% tinh theo du'p'c li§u kho ki^t. Dya tren k i t qua thyc t i v i chuyin iuin son tra trong DBVN IV, d i nghj du'a ra giai hgn ty l§ tro toan phan trong du'p'c liiu t i o meo la khong qua 9,0%.

Kim lofii nang

^ K i t q u i x i c dinh ham lu-p-ng kim logi ngng ciJa 3 m l u du'yc li$u bang phu'ang phap so m i u

cho thiy mau cua c i c i n g dung djch thi> deu nh^t han m i u cua ong dung djch d i i chiiu cd nong dp ehl la 10 ppm. Dya trin k i t qua thyc t i , de nghj du'a ra gid-i hgn kim loai ning cua du'^c lieu tao m i o l i khong qua 10 ppm.

Ty 1^ vyn nat

K i t qua x i c dinh ty Ip vyn n i t cua 3 m i u duve lipu du'p'c trinh b i y 6 bang 6.

Lin thir

Bang 6: Ty 1$ wn nat cua dum lieu tio m^

Tyl$(%) MiuTM2(g} Tyl^(%) Maum3(g) T^i^m

TRingblnh±SD(%)

T*P CHi^DU-aC H g c - 9/2016 (SO 485 NAM 56)

(5)

• Nghien ciru - Ky thuat

K i t qua bang 6 cho thiy ty l# vgn nat cOa 3 mau duvcjipu la khoang 0,700,87%. Dya ti«n k i t q u i thyc te va chuygn luan son tra trong DDVN IV, de nghj dua ra gidi hpn t j Ip vun nat cCIa duvc ll^ii tao meo la khdng qua 2,0%.

Kltlu^n

Da xay dyng dupc tieu chuin chat lupng cua qua tao map (Fructus Docyniae indicae) vin mdt se ch! tl6u gom: md ta. djnh tinh, dd i m , dinh lypng, tro toan phan. kim loai nang, t j Ip vun nat.

TiSu chuin nay c6 t h i ap dung de kiim tra va danh gia chit lupng duvc Ilpu tap mSp trSn thi trovng hipn nay

Loi cam o n ; Npi dung cOa nghi&n cuu nSy la mpt phin npi dung cOa dS tai ma s6 KHCN- TB.04C/13-18 duvc tai tno bdl Chuvng trinh "Khoa hoc va Cdng ngh0 phyc vy phat triin b i n vijng vung Tay Bic" ma s6 KHCN-TB/13-18 do Dai hpc Quic gia Ha NOi la Co quan chu tri.

Tii lieu tham khao 1. B 5 Tit Lpi (2004). NhOng cSy thuic vi vi thuic Vi4t Nam, Nxb. Y hpc. Ha Hd, tiang 355.357.

2 Vi#n Dupc lieu (2004), C3y/hu(5ci«di3ngv§t/dm ffiuoc * Vi^t Nam, tip 2, Nxb. Khoa hpc va Ky thuSt, HS NOI, trang 785-787.

3. Bd Y t i (2009), Duvc diin V4I Nam IV, chuyin iuin Son tra. Nxb. Y hpc. Ha Npi, trang 885-886.

(Ngay nhin bai: 23/06/2016 - Ngiy duyit ding: 01/0g/2016)

N g h i e n Clhl d i i u Cllg... (niptheotrang Tiin hanh do khii pho MS tren mSy Quatro micro TM API. P h i MS thu dypc dinh tuong irng vdi minh m/z = 2 4 1 , 1 phii hpp khii lupng phan til ciia acid mefenamic (C^H.^NO,, P.ti: 241,29).

Bo pho NMR trong dung moi MeOH, t i n sd 500 Hz. P h i NMR thu dupc phii hpp cau tnjc dy doan cCia acid mefenamic.

K i t q u i ciJa cac phuvng phap xac d|nh c i u tnic, dp tinh khiit, cho thiy s i n phim phu hpp vdi c i u tnjc dy dean. San phim acid mefenamic tinh khiit.

Ban lu^n

Hi$u suit sau khi t i i yu hpa dat 60 12% Hiju suit chua that la cao. Diiu nay cd t h i do trong c i u tnJc cOa trimethylanilin cap dipn tO- tiin nhdm NH, lien hpp vol nhan lam giam mat dd dipn tu dan d i n phan ling x i y ra khd khan hpn. Nhdm CH, cOng cd t h i gay can t n i khdng gian. Chiing tdi chua tim thiy hipu suit ma cac nghldn cilu tren the gioi thyc hljn d i so sanh. Tuy nhidn d i i chiiu vdi cac phan ling tuong V cho thiy thl hipu suit giao ddng tCr 50-70% tuy thu«c vao c i u tnjc va xuc tac. Trong thdi gian tdi chiing tdi se khap sat anh hudng cua xiic tac d l nang cao hipu suit Y i u t i nhipt dO cung anh hydng manh d i n hipu suit cac phan Cpng thudng tlin hanh * nhipt dO cac Tuy nhien nhiJt dd cap cung d i d i n d i n phan hu}

san pham tao tpp.

'68;

Ket lu$n

Til nhu'ng nguyen Ilpu dpn gian, d i kiim d Vi^t Nam, chiing tdi da xay dyng dypc quy trinh ting hpp acid mefenamic - mOt thuic giSm dau khang vidm nonsteroid hijn dang duvc nhiiu nha may dupc d Vi#t Nam si> dyng d i s i n xuit cac c h i pham thudc. Quy trinh dypc toi yu hda bing phin m i m MODDE 5.0. Quy trinh don gian, phii hpp vdi diiu ki$n d Vi$t Nam, cd tinh ling dgng cao.

Tii lif u thain khao 1. Richard B. Upton, Walter F. Stswait. Seymour Diamond, Merle L. Diamond, Michael Reed (2001) Prevalence and burden of migraine in the United States- Data from the American migraine study II", The J of HeadandFace Pain 41(7), p. 646-657.

,1, ^ ; , i : ' . " ' " ^ ' ^ ' " " ' ' P " " ) . "Thyc tiang v i mot s6 thay ddl giai phiu, iti loen co nang vi b^nh IV d phy nS quanh tu6l man kinh". Tap chi Khoa hpc vi Cdng nghi.

no( i), tr. 155-162

3. BP2013, CD- rem, "Add mefenamic".

4. Genbao Zhang, Weidong Fan, Caillan Xla (2009) Hmcess for prepanng mefenamic acid CN101475505

eJcNlm^feW'^'"' ""^ ' " ™ * ™ *

™ r L r f ' ' " i * ° 2 . ^ ° " = ' ^"^^ '•' f^O'^)' Pmductkm method of mefenamic aad CN1023443S4 (A)

7ChrislianWolf,ShuanglongLiij,XuefBngMel,Adam T August, Michael D. Casimir (2006), •R4loselertte copper^afalyzed aminaHon of bromoberSoic aciS using aliphalio and aromatc amines". The Journal^

Organic Oiem'istry. 71(8), p. 3270-3273.

(Ngiy nhin bii: 12/08/2015 - Ngiy duy$t ding: 01/030016)

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