Tfp chl THONG TIN Y DUQC
I ^ nutn AVii.chuygn mdn cua ngu'di tryc tigp bdn thudc chu yeu la DSTH (51,5%), 2,3% Id khdng e6 chuygn mdn ve dudc.
- Da so cdc CSBLT cd 2 ngudi Idm viee.
TAI LIEU THAM KHAO
1. B$ Y te*: Nguyfin tSc, tifiu chuiin "Thijt hiinh \&\.
nhS thuoc". Ban hinh kSm theo QuySt dinh sd n/2007/QO-B)Tngiy 24/01/2007.
2. B$ Y \&. B6 sung mpt sfi n^i dung ciia nguygn tSc, B&u chuSn "Thyt hSnh t6t nhi thuSc". C^y&: dinh s6 29/2007/QD-BYT, ban hAnh AAn Oieo QuySt dmh s611/2007/QD-BYT ngiy 24/01/2007.
3. Chinh Phu: Ph6 duy^ "Chign lutjc phSt trlgn ng&nh dul?c glal do^n dgn 2010". QuySt djnh s6 lOa/2002/QO-ng. ban hinh ngiy 15/8/2002.
CMC Thffng kd KiSn Giang: Bio cio thdng kg dSn sfi Kign Giang nSm 2007. Ci^c Thdng ki Kiin Giang, 2007.
Qutfc yM)\ nu'dc CHXHCN Vi$t Nam: Lu^ Din;fc, sfi 34/2005-QHll. Qu6c h& nutk OiXHOV W^
Nam khda XI, k^ hgp thu" 7, »i8ng qua ngiy 14/6/2005-
Sd Y t«f Kidn Giang - Phdng Quin IV Dif^: Bte cdo cdng tic dul;fc nSm 2007 v i phuidng hiAihg ho?t d$ng nim 2008. Sd YtiKiin Giang, 2007.
Sd Y te Ki&n Giang: Bio cio cfing tdc dutjfc 06 thing dSu nSm 2008 v i phuOng hulSng ho^t d§ng 6 thing cudl nSm 2008. Sd Yt^iOin Giang, 2008.
Trang tAm Y tg thinh phd R^di GU: B6o cio danh sich hinh nghg y duljc tu" nhSn trSn dja bin thinh phfi l^ch Gii nim 2007 vd 6 thing dau nSm 2008. SdYt^KISn Giang, 2007^
NGHEN Cliu T i W AN TOAN CUA 0|CH CHIET TOI DBV LY SON TRflV THUC NGHEM
VO Binh Du'dng'f Nguyen Vin Long', Trlnh Nam Trung , Nguyen Minh Chinh*
TOM TAT
Muc tieu: dinh gii ddc b'nh cap (DTC) vi ddc ti'nh bin tnfdng dien (DTBTD) cua dich chiet tdi den Ly Sdn tren ddng vat thu'c nghiem. Ddi tu'dng vi phu'dng phip: thd nghiim danh gia DTC cua djch chiet tdi den Ly Sdn trin chudt nhit dung dudng udng theo phudng phip cua Abrham W.B., Turner A.; thd nghiem DTBTD tren thd udng dfch chiet tiii den Ly Sdn hang ngiy
vdi lieu 2 g/kg/24h va 4 g/kg/24h trong 42 ngay. KSt qui: chda tim thay LDso, vdl lieu udng tdi da mi chudt cd die uong dudc (10 g/kg trgng ludng cd the) khdng gay chet ddng vit thuC nghiem. Tren tho, djch chiet tdi den Ly Sdn d cac mdc lieu 2 g vi 4 g/kg/24 gid uong hang ngiy trong 42 ngay khdng inh hudng den si/phit trien trong lu^ng cd the, cac chi so diin tim, huyet hoc, sinh hda vi md binh hgc gan, lich, than thd. Ket la$n: dich chiit tdi den Ly Sdn cd ti'nh an toin cao tren ddng vat thdc nghiim.
SUMMARY
Study on safety of Ly Son black garlic extract in experiment
OJectives: study acute and subchronic toxicity of Lyson black garlic extract on experimental animals. Methods: applying method of Abraham W.B and Turner A to study the acute toxicity of Lyson black garilc extract administered orally on mice; study the subchronic toxicity on rabbits with a daily dosage of 2.0 gr/kg and 4.0 gr/kg in 42 days. Results: LDso W3S not found, the maximum permissible dose (10 gr/kg body weight) did not kill experimental mice. In rabbits, Lyson black garilc extract administered orally with the daily dose of 2.0 gr/kg and 4.0 gr/kg in 42 days did not affect body weight gain and parameters such as ECG, hematology, biochemical and histology of liver, kidney, spleen. Conclusions: Lyson black garlic extract Is highly safe on experimental animals.
I . GAT VAN DE
Tdi den la san pham lgn men tiJ* tdi tudi bdng each xy ly d digu kien nhiet dp vd dd am tiiich hdp trong tiidi gian ddi. San pham tiiu du'dc c6 mdu den, vi ngpt tiai cdy, cd the bdo qudn lau ngay de sd dung [5]. Cac nghign OJU cho ttiay.
sdn pham \a] den cd nhieu tac dung vudt trpi so vdi tdi tudi nhy tac dung chdng dxy hoa, kich tiiich mien djdi, ut che te tao ung ttiy,...
[4,6,7]. Vi v^y, san pham t6i den da vd dang dudc sy dyng pho bien trong nganh cdng nghi thut pham, du^c pham d Nhdt Ban, Han QUOQ...
*TS., Hoc vien Quan y
I ^If »,»•» X £i\^iy\j i i i \ I UV^fi^
So 9 ndm 2012
Hlnh 1: Tdi Ly Sdn tudi (a) vi tiii Ly Sdn sau khi len men - Aw den (b).
a Viet Nam, Hpc vien Quan y da nghien cdu thanh cdng lgn men ldi den t y nguon tdi Ly Sdn (Qudng Ngdi). Sdn pham thu du'dc cd mau den, vj ngpt, khdng con miji hdng eua tdi tu'di (hinh 1). De djnh hu'dng phat trien cac san pham t y tdi den Ly Sdn phuc vu cham soc sye khde cdng ddng, chung toi ddnh gid ti'nh an todn cua dich chiet toi den Ly Sdn nhdm ddnh gia DTC va DTBTD cua djch chiet tdi den Ly Sdn tren dpng vdt thye nghiem.
I I . D O I T U C T N G V A P H U O N G PHAP 1. Ddi Mdng nghien cihi - Che pham nghien cuti: tdi den Ly Sdn (Hpc vien Quan y, sdn xuat thang 3/2012), dat Tidu chuan cd sd. Tdi den di/dc dieu che thanh djch ehiet dang cao dac 2 : 1 , diJng de danh gia ddc ti'nh.
- Ddng vdt thi nghiem du'dc nudi du'dng tnang dieu kien phdng thi nghiem 5 ngdy tru'dc Idii tien hanh nghign ciJu, gom:
+ Chudt nhat trang khde manh, trgng lu'dng 20-22 g, dat tieu chudn thf nghiem.
+ Thd nha khde manh, trpng lu'dng 1,8-2,2 kg, dat tieu chuan thi nghiem.
- Dung eu, mdy mdc: mdy xet nghiem sinh hda t y ddng; mdy dem hong cau, bach cau t y ddng; bp dyng cu mo ddng vdt ^ nhd; can cliinh xdc 10"^ mg, bdm kim tigm,...
2. Phu'dng phap nghien cu'u 2.1. Nghien cuU dgc ti'nh:
- Theo phu'dng phap eua Abrham W.B., Turner A. vd theo quy djnh cua To chyc Y te
Thg gidi vd Bp y te Vigt Nam ve nghien cyu ddc tfnh cua thudc [1,3].
- DTC: chudt nhdt trdng du'dc ehia thdnh cac Id, moi Id 12 con, cho udng dich chiet tdi den (3:1) vdi cdc myc llgu tdng dan, den lieu gdy chet 100% s6 chudt. Sau khi dung thuSc, chupt du'dc nudl dudng vd theo doi trong 72 gid. Xdc djnh sd chudt chet theo tiihg nhdm th! nghigm. Tfnh todn theo phu'dng phdp cdi tien cua Livsehitz P.Z. [2].
-DT¥TD: thSdutX: chia tiidnh 3 Id, m5i 1612con + Ld 1: uong nude muoi sinh ly (2 ml/kg/24 h).
+1£ 2; uong didi diia tdi den (2 g/kg/24 h).
+ Ld 3: uong djdi chi^ toi den (4 g/kg/24 h).
2.2. dc chi tieu danh gii: hoat dong, dn udng, trpng ludng cd t h ^ (TLCT), dien tlm, huyet hpc, sinh hda (bdt dau nghign ciJTu, sau 3 tuan, sau 6 tuan nghien culi), md benh hpe gan, lach, than (khi ket thuc thy nghiem).
2.2. Xd ly so lieu: bSng phan mgm StartvlevK 2.0.
I I I . KET QUA VA BAN LUAN
1. DTC cua dich chiet tdi den Ly Sdn tren chupt tiii nghiem
Vdi cdc myc lieu cho udng tang dan (3; 4;
5; 6; 7; 8; 9 vd 10 g/kg TLCT chupt), chudt d cac Id deu an udng hoat ddng binh thu'dng.
Theo ddi sau 72 gid khdng ed chudt chet (ke ca myc lieu tdi da ed the du'a vao da day chudt 10 g/kg/24 h). Nhu" vay, chuS tim tiiay LD50 cua dieh chigt tdi den Ly Sdn tren chupt nhat trang theo du'dng udng. Dieu nay cho thay, djch chiet tdi den cd do an todn cao trgn dgng vdt thye nghiem.
2. DTBTD cua dich chiet bii den Ly Sdn tren tho thi nghiem
Bang 1: Anh hddng cua dich chiet toi den LySdn ddi vdi TLCT tiio (n=12)
Th^diem xet nghiSm Tru'dc ttii nqhiem (a)
£au3tLen(b) Saietmnfc) P
ncT (k Lo chutig
(i)
1,99±0,12 2,06±0,12 2,21±0,11
Lddich chiS tieu 1
(2) 1,98±0,13 2,09±0,12 2,22±0,11
VX±SD}
Lodich chi€tii§u2
(3) 1,96±0,10 2,10±0,12 2,22±0,12
<0,01
P
/^-i>0,05 /^-2>0,05 Pj.i>0,05
So sanh TLCT cua tiid d hai Id diJng djch chiet tdi den vdi Id chutig tei cdc thdi diem thay thay doi khong cd y nghTa thdng kg (/;>0,05). So sanh giffa cac thdi diem sau so vdl tru'dc thay, TLCT thd d ca 3 Id deu tang ed y nghia thdng ke (/7<0,01). Nhti vdy, djch chiet tdi den Ly Sdn khdng lam thay ddi bat thu'dng ve trpng lu'dng cd the ciia thd.
Tfp chi THdNG TIN YDUQC
JU y iiuni ^\JL£,Bing 2: Anh hudng cua dich chiSt tiii den ddl vdi di^n tim thd dd^o tiinh Dg (n=12).
Thdi ai^m xM nghiem Lo chitng (1) TSn sStim Tnfik thl nghidm (a)
Sau 3 tuan (b) Sau 6 tuSn (c) P
238,17±33,53 255,51±34,81 241,33±32,31
Ld cao ldng lltul(2)
LS cao tdng
liiSu2(3) P
(CK/ptlllt, 'xtSD) 262,61±42,64 245,20±35,91 257,62±41,81
256,39*31,25 243,12±30,37 255,39±31,96 a..>0,05: fl-.h>0,05: fl.,>0,05
A-i>0,05 Pj.i>tS,OS /?j.i>0,05
Bl^n(K(mV, XiSDJ TnfiSc thi nghidm (a)
Sau 3 tu5n (b) Sau 6 tu5n (c) P S6ng bat thuOnfl
So sanh trong tifng 16 tht nghidm v^ so sdnh g mot th6i diem, tSn so va tim tho thay doi Ichong c6 (/?>0,05). Khong co song
0,376±0,047 1 0,388±0,062 0,390±0,069 0,379±0,051 0,374±0,044 1 0,391*0,073
0,379±0,021 0,381*0,084 0,382±0j068 a..>0,05; fl-.fc>0,05; fl...>0,05 Kh6nq 1 Kh6ng 1 Kh6ng jiQa c i c thdi dl^m
'ia cAc Id d cung bi§n dp cua di^n y nghla thong i<§
bat thu'dng tren
A-i>0,05 A-2>0,0S ft.i>0,05
di^n tim cua cdc Id th6 tai cac thdi diem nghlSn cu\j.
Nhu" vay, dich chiet to! den Ly Sdn Ithong lam xuat hien cdc bien doi bat thu'dng ve nhjp tim cua tho.
Bing 3: Anh hudng cua dich chiet tdi den ddi vdi mdt sdchl tieu huyet hgc cua did (n=12) Than diem xet nghi$m Ld chitng (1) LScaoldng
lieu 1(2)
L£caoldng
iieu2(3) P
SSIutmn hdnn cau (x lif'/t, x±SDJ TnJ^thingtmn (a)
Sau 3 tuan (b) Sau 6 tuan (c) P
5,47±0,89 5,93±1,19 5,72±0,22
5,59*0,75 5,81*1,13 5,49*0,58
5,89*0,68 6,29*1,35 6,11*103 fl-.>0,05: aj,>0,05; ».h>0,05
Ai>0,05 A J > 0 , 0 5 Ai>0l05
So iuvna huylt sic to (X q/i, X±SD) Tnitk Itii nghiem (a)
Sau 3 tuan (b) Sau 6 tuan (c) P
116,21±20,75 131,57±14,21 126,12±10J1
129,21*21,06 123,75*15,89 135,94*12,75
126,28*18,62 129,63*13,96 133,29*17,12 ft.,>0,OS; A<>0,05: a-i,>0,05
A.i>0/B fti>0/!5 fti>0/)5
seiutfno bach cSu (x llf/i, X ±SDI TrutJb tiiingtii^ (a)
Sau 3 tuan (b) Sau 6 tuan (c) P TnM:ttingHim(a) Sau 3 tuan (b) Sau 6 tuan (c) P
5,33±1,21 4,94*1,18 4,87*0,95
5,41*1,24 5,52*0,95 5,05*1,06
5,28*0,91 5,14*1,03 5,01*0,87
»..>0,05; (V.>0,05; »*>0,05 S6iupng ti^ cau (X l(fA X±SD) 288,97*58,61
298,32*67,26 303,84*49,91
292,13*45,14 308,54*58,41 312,68*60,73
296,91*51,48 311,12*62,52 301,57*6737
»..>0,05; fl„>0,05; »*>0,05
fti>0,05 Aj>0fl5 a,>0/15
ft,>0/)5 flB>0,05 A.,>0fl5
So sanh trong tiitig Id giiJa cdc thdi diem thl So sanh trong tiftig Id giii^ cdc thdi digm thf nghiem vd so sanh gi&a cdc 16 d cung mdt thdi diem, cac chi sd huygt hgc cua thd nghign cuti (sd lu'dng hong cau, huygt sde td, bach
m-K' w ^ . ^ , j ^ T - g - " f — 1 1
cau, tieu cau) thay doi khong cd y nghTa tiiong kg (/7>0,05).
Nhy vay, djch chiet ldi den Ly Sdn khdng lam thay ddl d i u t ndng tao mdu cua ddng vdt t h y t nghiem tronq qud tnnh thy.
Jvyl*VJ ±iiy 1 MJ%J\f\.^
So 9 nam 2012
Bang 4: Anh hddng cua didi chiet Ixil den ddi vdi chut ning gan. tiiin cua thd (n=10) ThaV diSm x4t nghiem j LdchiHigfl} \L6caol6nQmil(2)iL6caoldnglfSu2f3^ p
Hoat do enzym AST (U/i, X ±SD) Trutit thl nghiem (a)
Sau 3 tuan (b) Sau 6 tuan (c) P
59,03±M35 58,75± 17,62 59,47±18,66
61,42± 11,18 59,48±19,83 60,34±20,09
58,59±15,81 61,35±23,46 61,59±19,89 fl:..>0,05; a.a>0,05; ft.h>0,05
/3si>0,05 ya2>0,05
Hoat do enzym AL T (U/l, X ±SD) Trutk thi nqhiem (a)
Sau 3 t u 3 n ( b ) Sau 6 t u a n (c) P
99,61±12,13 102,11± 15,37 102,69± 16,24
104,01±15,41 107,95± 13,05 103,76± 17,68
102,54±17,68 107,85±18,24 105,27*1637 ft.B>0,05; a-a>0,05; ft-b>0,05
/^i>0,05 A2>0,05 A i > 0 ' 0 5
t^ng do creatinin mau (ijmol/i, X±SD}
Tni6t: thi nqhiem (a) Sau 3 tuan (b) Sau 6 t u a n (c)
63,01±9,03 59,37±8,94 57,48±8,73
62,36±9,74 56,51±8,91 57,32±9,08
64,41±11,70 54,37±10,85 52,88±9,93 fl--,>0,05; A,-a>0,05; fl:b>0,05
A-2>0,05 A i > 0 , 0 5
Nong do ure mau (mmol/l. X±SD) Tnj6l:tty'nqhiem (a)
Sau 3 tuan ( b ) Sau 6 t u a n (c)
So sdnh trong tiihg Id g thf nghiem vd so sdnh giuS thdi diem, hoat do enzym hdm li/dng creatinin mau, he thay doi Widng cd y nghTa t Nhi/ vay, djch chiet tdi den bign doi bat tiiu'dng cac chu cua dpng vdt t h i nghiem.
* KSqua mo benh hpc tang Quan sdt dai the bang m kfnh lup cd dp phdng dai 25 hinh thai ciia gan, lach vd t djch chiet tiiii den khdng khdc Ket qua nghien cuti ve md tiian thd d i o thay, djch chiet t udng vdi ligu 2 ml/kg/24 gid va lien tiJC tiong 42 ngay khdng c gan, tiian, lach cua tiid.
I V . KET LUAN
- Chua xac djnh dudc LDjc Lieu tcH da md chudt co ttie u6 khdng gay chet ddng vat tiiyc - Djch chiet tdi den eho tu'dng yng 2 g vd 4 g/kg T ngay khdng dnh hu'dng d g phdt trien trpng lu'dng cd t cd quan tao mdu, khdng an ndng vd md benh hgc gan, t
4,12±0,91 4,09±0,89 4,12±1,01
ft-a>0 iJa cac thdi diem :ac Id d eiing mpt AST, enzym ALT, m lu'dng ure mau dng ke ( / J > 0 , 0 5 ) . Ly Sdn khdng lam c nang gan, than
aJa ttio tfli nghiem:
at thu'dng va du'di an thay: mau sac, i a n d hai Id diing
so vdi chyng.
benh hpe gan, Ideh, 61 den diing du'dng
lieu 4 ml/kg/24 gid ay ton tiiudng tign
tiieo dudng udng.
ng la 10 g/kg TLCT nghiem.
t h d uong vdi lieu LCT/24h trong 42 n dien tim vd sy e, khdng dgc vdi 1 hu'dng den chyc
an, Ideh.
4 , 0 8 ± 1 , 0 1 4 , 0 2 ± 1 , 1 0 3 , 9 7 ± 0 , 9 4
3,97±0,89 3,96±0,85 3 , 9 9 ± 0 , 9 1 05; A,.a>0,05; ft.b>0,05
jCfe>0,05 Ai>0,05
- C a c k e t q u a n g h i e n CIJIJ t r e n e h o t h a y d j c h e h i e t t d i d e n L y S d n e d ti'nh a n t o a n e a o t r g n d d n g v a t t h u ' c n g h i e m .
T A I L I E U T H A M KHAO
1. Bo Y t e : Q U I dinii ve nghien cuU dUdc ly cac thuoc y hoc c5 truyen dan tgc. Quyet dmh 371/QD-YT; ngay 12/3/1996.
2 N g u y S n X u a n P h a c h vk CS: Tfnh toan thong ke va tin hoc uTig dung tnang sinh y duWc. iiiha xuat ban Quin dgi nhin dan, 1995, tr.l46-l'f9.
3 A b r h a m W . B . : Techniques of Animal and Qinical toxrcology. Wetf. Pub. Chicago, 1978, pp.55-68.
4 C h u Q.J., Lee D.T.W., Tsao S.W., W a n g X . H . , W o n g Y.C.: S-allylcysteine, a water-soluble garlic denvadve, suppresses the growth of a human androgen independent prostate cancer xenograft, CWR22R, under in vivo conditions. BJU International, 2007, 99, pp.925-932.
5 M o n t a n e A., Casado F.]., C a s t r o A., S o n c h e z A . H . , R e j a n o L.: Vitamin content and amino acid composition of pickled garlic processed witfi and without fermentation. Joumal of Agricultural and RxxlChemistry, 52, 2004, pp.7324-7330.
6 M u n d o H.M.N., A d a y a S.D., M a l d o n a d o P.D., A n a t e G.5., M a r t i n e z A.L., Cruz P.V., e t a l : S- allylcysteine prevents the rat from 3-nitropropionic acid-Induced hyperactivity, early markers of oxidative stress and mitochondrial dysfunction.
Neuroscience Research, 2006,56, pp.39-44.
7 S h i n J . H . , C h o i D . ] . , L e e S.J., Cha J.Y., K i m J . G . , S u n g N.3.: Ctianges o f physicochemica components and anticwidant acbvity o f garlic during its processing. Journal of Life Science, 2008,18, pp.1123-1131.Si
