Journal of research in via nam uadllional medicine andpharmacy
N G H I E N C U t J D Q C T I N H B A N T R U ' d N G D I E N C U A V I E N N E N T R A N G P H U C L I N H P L U S T R E N C H U O T C O N G T R A N G T H l T C N G H I E M S t u d y o n s u b - c h r o n i c t o x i c i t y o f T r a n g p h u c l m h p l u s t a b l e t s i n
e x p e r i m e n t a l r a t s
* Nguyen C h i DOng ' , • * D a n T h n y D m m g ^
*** Nguyen T r l n G i i n g H m m g ',"•» N g u y i n T r p n g T h o n g "
' Trung Idm Duffc ly lam sing - Truemg BH YHN,'Bo mon Dmrciy-Truang DHYHN
^ ^ T 6 m t i t
^ ^ ^ ^ ^ N g h i e n du dfc linb ban a-uang diln cua Vien nin Trang Phye Linh Pius (VNTPLP) lr«, chudt cdng trdng Ibvc ngl,i4m. Bii nrfng va phumg phdp nghien ciru: N^ien cm, doc linb bdn truang d,en Iren chuQI cdng Irdng tbeo ducmg u^g Kh qud: Khdng cd sa khde biel vi cdn ndng va lmh b-gng cbung giUa Id ching va cdc id H Sau 12 ludn ngbien aiu. VNTPLP Ichdng gay Ihay da, dang ke ve chuc nang Igo mdu. cbuc nang gan Ibgn. dgi tbi cdc ca quan vd vi Ihi gan Ibgn ebugl sa vdi 16 chung Ket lufn: VNTPLP khdng gdy ddc linb bdn trudng dih, tren chugl cdng irang kh, cho chugl udng liiu 327 mgfkg/ngdy vd liiu 981 mg/kg/nggy Irong 12 ludn iien tyc
Tir khda: Vien aia T r d n g Phpc Linb Plus, Hpi chihig rufit Uch Ihich Summary
S T U D Y O N S U B - C H R O N I C T O X I C I T Y O F T R A N G P H U C L I N H P L U S T A B L E T S I N E X P E R I M E N T A L R A T S
Objealves: To examine sub-chronic loxicily of Trang pbuc iinh plus tablets (VNTPLP) in experimental rats. Subjects and melhods: ,be sub-cbronic loxicily qf VNTPLP yi-as examined by repeated grai dose in Wisiar rats. Resulls: There were na significan, differences in general status and body weigbl between treated animal grgup gnd cgnlral animal group VNTPLP did no, show any changes in baemalglogical. biacbemical parameters and hislgpaihology af liver and kidney in axf^rmm,,,; animals after 12 weeks of treatment Conclustan: Ihe grglly ofsub-chrgnic loxicily of VNTPLP bas not been determined al Ibe dose ofmmgflcg/day and 9aimg/kg/day.
Key words: T r a n g pbuc linb Plus tablets; Irritable Bowel Syndrome.
p|a cbi liin b ; : Nguyjn Chi Dung - Trung i ™ Duoc ly I t o sang Neiv nhan bil- IMnmf.
Dia chi email: nguyenchidung.hn,u@Bn,ail.con, N S V obin WSn m ™ < : Phan biin khoa hfc: PGS.TS. TiJn Ou6c Blnh » • „ ? ' 12/5/2016
• BS; "TTlS. ••• PGS.TS ' ™ vuoc Binn Ngay lUng bao: 24/6/2016
NgbUn clhl YDBCT Viet Nam L BAT VAN DE
Hpi chiing rupt kich thich (HCRKT) Id tmh ttMig r i i lopn chiic ndng rupt pho biin, tdi di tdi l^i nhifiu lln md khong tim thiy bit ky tfin thuong can true hay rfii loan shih hfia ndo. HCRKT dnh hudng ddng k i toi chit lupng cufic sing, Idm gidm ndng suat lao dpng va gay ton kem ttong vific diiu ttj [1]. Vi vdy d Vifit Nam, vific thn kiim, nghien ciiu nhihig thuoc diiu ttj HCRKT hifiu qud vd an todn Id mpt vin di d p thiit. Immune Gamma dupc chiet tach tir thdnh ciia t i bdo vi khudn Lactobacillus fermentum, cd tdc dyng tdng cudng hfi mien djch, cdn bdng hfi vi suih vpt dudng rufit, tdi tpo nifim mpc [2]. 5 hydroxyttiptophan (5 - HTP) Id chit ttung gian ttong qud trinh chuyin hfia tiyptophan thdnh serotonin, giiip diiu hfia nhu dpng vd su bdi tiit ciia rufit, cdi thifin trifiu chirng dau byng vd khd chju hong hpi chiing rupt kich thich (31. Vific kit hpp Immune Gamma, 5 - HTP vdi nhiing thdo dupc quen thufic ditag diiu tti bfinh ly dudng tieu hda Id Bpch teudt, Bpch phpc linh, Bpch thupc vd Hodng bd ttong Vien nen Triing Phpc Linh Plus (VNTPLP) hua hpn trien vpng du phdng vd dieu ttj HCRKT. Trong nghien ciiu ndy, mpc tifiu:
Ddnh gid d0c tinh ban truing dUtt ciia VNTPLP Iren th^c nghifm.
n . CHAT L i f U, D 6 I TUONG VA PHU'ONG P H A P N G H r t N ClTU
2.1. C h i t lipu nghien ciru VNTPLP duijic bdo chi dudi d^ng vifin nen bao phim do Cfing ty TNHH Tu vin Y dupc Qufic t i (IMC) san xult va cung d p . Thdnh phin mpt VNTPLP gfim 100 mg Immune Gamma, 200 mg cao Bpch ttupt, 50 mg cao Bach phpc Iinh, 50 mg cao B^ch thupc, 50 mg cao Hodng bd vd 3 mg 5 - HTP. Liiu khuyin cdo sii dyng ttfin ldm sdng Id 54,5 mg/kg/ngdy, lieu ngopi suy ttfin chufit cong la 327mg/kg/ngdy (hfi so 6).
2.2. D i i ttrpng nghien cihi Chupt cong chiing Wistar, long ttdng, cdn ndng 180 ± 20g, do Hpc vifin Quan Y cung d p . Dpng vpt thi nghipm dupc nufii ttong phfing thi nghifim 10 ngay ttudc khi nghifin ciru bdng thiic dn chuan, ufing nudc tp do,
2.3. Phuong phap nghien ciru Nghifin Cliu dpc tmh ban ttudng diln tten chufit cong ttdng theo hudng ddn ciia WHO, cho chufit sir dyng thuoc theo dudng uing [4]:
Chufit dupc chia ldm 3 16, mfii 16 10 con. Lfi chiing: uing nudc cat Iml/lOOg/ngdy. Lfi trj 1: uing VNTPLP liiu 327 mg/kg/ngay. L6 Irj 2: uong VNTPLP lieu 981 mg/kg/ngdy (gip 3 lln 16 trj 1). Chufit dupc uong nudc hodc VNTPLP ttong 12 tuan, ngdy mfit lln vao buoi sdng.
J
Joumal af research in vie, nam tradaional medidne andplumnacy Na 49-2016 2.4. Dja diem nghien clhi: Bp
mfin Duprc ly - Trudng Dji hoc Y Hd Npi.
Cac chi tieu theo doi truac va trong qud trinh nghien eieu:
- Tmh tt^g chung, thi ttpng ciia chufit
- Danh gia chiio phan tao man: sfi lupng hing clu, thi ti'ch ttung bmh hong can, hemoglobm, hematocrit, sfi lupng bach cau, ti lfi lympho vd sfi lu- png tifiu clu.
^ ^ ^ Ddnh gid chiic ndng gan:
bilmibin todn phin, albumm vd cholesterol todn phin.
- Danh gid miic dp hiiy hoai ti bdo gan: ALT, AST.
- Ddnh gid chiic ndng thdn: ning dp creatmm huyit thanh.
Cdc fliong si theo doi dupc kiem tta vdo ttudc luc uing thuic (TO), sau 4 hiln uong thuoc (T4), sau 8 min
udng flmic (T8) vd sau 12 tain ufing thufic (T12).
Md benh hpc: Sau 12 tain ufing thufic, chupt duac mfi di quan sdt dpi flifi todn bp cac CO quan. Kiim tta ngdu nhifin clu tnic vi thi gan, flian ciia 30% sfi chupt d moi 16. Cdc xfit nghipm vi thfi dupc thuc hifin tpi Trung tdm Nghifin ciiu va phdt hifin sdm Ung fliu (do PGS.TS. Lfi Dmh Roanh dpc kit qud vi thi).
Xir ly s6 lieu: Cac so lieu nghien Cliu dupc xii ly fliing ke flieo phuang phap t-test Stadent. Sfi lifiu duoc biiu diln dudi dang : X± SD. Su khac bifit cd y nghla khi p < 0,05.
HI. KtT QUA vA BAN L U A N 3.1. Tinh trpng chung va sir thay doi the trpng cua chupt
Trong flidi gian flu nghifim, chupt d lfi chung vd cdc lfi uing VNTPLP hoat dfing binh fliuomg, nhanh nhpn, dn uing tot, phdn khfi.
Bang 3.1. Anh httdng cua VNTPLP din thi trpng cua chupt Lfi
Chirng Tril Tri 2
n 10 10 10
T0(g) 165,00 ± 15,99 166,50 ± 11,80 167,50 ± 18,75
T4(g) 199,50 ± 38,83 194,50 ±16,24 195,50 ±37,82
T8(g) 213,50 ±44,48 213,50 ±25,72 213,00 ±34,09
TIZ (g) 215,00 ±48,36 216,00 ±26,85 219,00 ±28,46 (*: p< 0,05 Ichi so v&i id chimg)
Nhdn xet: Sau 4 tain, 8 tain vd 12 tain ufing fliuic flui, ttpng lupng chupt d cd 3 16 (16 Chung vd 2 16 tti) dfiu tdng so vdi ttudc khi nghifin dm. Khfing cd su khde bifit ttpng lupng chufit giOa 16 chimg vd cac 16 ding fliufic fliii tai cac flidi diim ddnh gid
Nghun cia YDHCT Viet Nam St 49-2016 3.2. Danh gla c h i c n i n g tao mau: Anh hiromg ciia VNTPLP den cac chi si bnyet hpc chnpt cong trang
Bang 3 J . Anh hudng C h i s i
HBC (10"/1)
HGB (g/dL)
HCT(%)
MCV (ft)
WBC (lO'/l)
Lympho
(%)
PLT(10'/1) Lfi Chiing
T r i l Tri 2 Chiing
T r i l Tri 2 Chiing
Tril Tri 2 Chiing
T r i l Tri 2 Chimg
T r i l Tri 2 Chiing
Fril Tri 2 Chung
Tri 1 Tri 2
n 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10
ciia VNTPLP den cac chi so TO
6,77 ±0,27 6,77 ± 0,59 6,82 ± 0,55 13,67 ±0,93 14,15 ±1,11 14,13 ±1,02 43,31 ±2,18 43,62 ± 3,42 43,50 ± 3,47 51,28 ±2,86 51,84±3.57 50,32 ±3,42 5,22 ± 1,53 4,69 ±0,67 5,19± 1,14 66,24 ± 4,96 68,27 ± 2,40 68,05 ±2,13 381,61*58,74 372,31±42,41 374,62±56,56
T4 6,72 ±1,82 7,14 ±0,63 7,42 ± 0,59 13,68 ±3,00 14,22 ±0,84 14,51 ±0,72 43,07 ±10,08 44,31 ±2,57 46,32 ±2,93 51,68 ±5,88 49,37 ± 2,29 48,21 ± 1,79
4,93 ±2,14 4,26 ±1,36 4,27 ±1,21 66,19 ±7,65 63,83 ±11,37 68,61 ± 10,05 330,40±161,01 381,20±57,63 368,50±53,03
luyet hpc chupt cong trdng T8
6,77 ± 0 , 6 8 6,26 ± 0,56 6,38 ± 0 , 5 3 13,67 ± 0 , 7 6 13,14 ± 0 , 7 2 13,09 ±0,65 43,20 ± 2,94 41,54 ± 2 , 2 7 40,82 ± 2 , 1 3 51,34 ± 3 , 1 9 53,32 ± 3,01 51,41 ±2,02 4,62 ± 1,45 4,49 ± 1,21 4,35 ± 1 , 4 3 66,29 ± 6,97 68,06 ± 8,85 62,90 ± 10,00 341,40±129,11 384,30±87,97 449,10± 101,69
TI2 6,77 ±0,72 6,36 ±0,79 6,43 ± 0,23 13,62 ±1,12 13,14±1,19 13,11 ±0,87 43,43 ± 3,72 40,88 ±3,28 41,37±I,92 49,00 ± 2,77 51,34 ±2,38 49,02 ±2,21 5,13 ±1,65 5,67 ±1,45 5,27 ±1,60 66,14 ±8,07 67,54 ±5,14 65,10 ±12,71 422,00±10I,38 404,90± 139,20 439,40±101,70 (•*•• p<0,05 Ichi so vai id chimg)
Nhpn xfit: Khong cd sy khac bifit ve cdc chi so huyit hpc (si lupng hing d u , s i lupng bpch d u , s i lupng lympho, Hemoglobm, Hematocrit, flifi tich ttung binh hing clu, so lupng tiiu
cau) giaa lfi chimg vd cdc lfi dimg thuoc thu tai cac thdi difim trudc uong thuoc (TO), sau uing Uiuic 4 tuan (T4), 8 tain (T8) vd 12 tain (T12) (P > 0,05)
'"•"Idofresearch In vUtnamaadmanat medicme and pharmacy No 49 - 2016
c u a r a w ^ ^ n " " * ' ! ' • ^ ^ ^ ^ . * ' " * " ^ 1 ' " * ' " « " 8 s a n , than: Anh httdng cua VNTPLP den cac chi so smh hda chupt cong trSng
Bang 3.3. Anh htrdng cua VNTPLP din cae chi s l sinh hoa chupt clng tring
(*: p < 0,05 khi so vai 16 chimg)
Nhjn xet: Kh6ng cd su khac bifit phfii, gan, Idch, tay, than vd hfi thing vfi cdc chi s i smh hda (AST, ALT,
Bihrubm todn phin. Cholesterol todn phin, Albumm, Creatmm) giira 16 chtmg vd cac 16 tti cac flidi diim ttirdc uong fliufic (TO), sau ufing thufic 4 hiln (T4), 8 tain (T8) va 12 tain (T12) (p>0,05).
3.4. Thay doi v i mfi benh hpc sau 12 tuin uong thuoc
- Dpi thi: Trfin tit cd cdc chufit fliyc nghifim: khfing cd bit ky ndo vfi hinh dnh dpi thfi ciia cac co quan tun.
tifiu hod cua chupt.
Vi the: (HE 400: Nhufim Hematoxylin - Eosm, dfi phdng dpi 400 lln)
Hinh thai vi the gan:
* Lfi chiing: Gan thodi hda nhe:
bdo taong te bdo gan cd it h i c sdng nho.
* Lo ttj 1: 1/3 mdu mfi hfinh hoc cd hmh dnh gan fliodi hda nhp: bao taong tfi bdo gan cd it h i c sdng nho.
2/3 mdu mfi bfinh hpc cd hmh anh vi thfi gan binh thudng.
Nghiin cvat YDHCT Viit Nam Sd 49'2016
* Lo tTj 2: 1/3 mlu mo benh hpc co hinh anh gan thoai hoa nhe: bao tirong t^ bao gan CO it hoc sang nho. 2/3 mau mo benh hpc co binh anh vi the gan binh thufmg.
^frm
Anh I: Hmh thdi vi the Anh 2: Hinh thdi vi thi Anh 3: Hinh thdi vi thi gan chu$t 16 chnng gan chuOt 16 trj 1 gan chu§t 16 trj 2
(chufit si 3) (chufit si 21) (chupt si 34) Te bao gan thoai hda nh( Ti bao gan blnh thuimg Ti bdo gan binh thuing
Hinh thdi vi thi than:
* Lo chimg: 2/3 mdu mfi bfinh hpc cd hinh dnh thodi hda nhp tfi bdo ing lupn gin: bdo taong ing lupn gin co it hoc sdng nhd. 1/3 mdu mfi bfinh hpc thdn bhih thudng.
* .Lfi trj 1: 1/3 mdu mfi benh hpc cd hinh dnh fliodi hda nhp ti bdo ong
lupn gin: bdo tuong ing lupn gin od It hoc sdng nhd. 2/3 mau mfi bfinh hpc thdn binh thufing.
* L6 tti 2: 1/3 mlu mfi bfinh hpc cd hinh dnh thodi hda nhp ti bdo ing luprn gan: bdo taong ing lupn gin cd it hic sdng nhd. 2/3 mlu mfi bpnh hpc thdn binh thudng.
Anh 4: Hinh thai vi the than chupt ifi chirng
(chupt si 8) Than binh thuing
Anh 5: Hinh thai vi thi than chupt Ifi trj 1
(chufit so 22) Thgn binh thuing
Anh 6: Hinh thdi vi thi thain chu^t Ifi trj 2
(chufit si 36) Th^n binh thuing
Joumal of research In vie, nam tradltumal medidne andpharmacy rv. KET LUAN
VNTPLP khfing gdy dpc tmh ban truomg difin tt^n chupt cing tring khi cho chupt uong lifiu 327 mg/kg/ngay (liiu ngoai suy taong duong liiu dung ttfin ngudi) vd liiu cao gip 3 lln (981 mg/kg/ngay) ttong 12 hidn lien tuc.
Tit cd cac chi si theo doi vi tinh ttpng
chung, cdn ndng, chiic ndng tao mdu, chuc nang gan, mirc dp huy hoai ti bao gan, chirc nang than va mfi bfinh hpc gan, thpn deu ndm trong gidi han binh thudng, khfing cd su khac bifit ro ret so vdi 16 chiing, kh6ng cd su khac bifit vdi p>0,05.
P
TAI Llfu THAM K H A O1. Romano C, Comito D, Famiani A, Calamara S, Loddo I (2013). Partially hydrolyzed guar gum m pediattic fimctional abdommal pam.
The Worid Joumal of Gastroenterology., Vol.19, pp: 235- 240.
2. Conway PL, et ai, (2005), Modulation of faecal enteric bactria and symptoms of uritable bowel syndrome using Lactobacillus fermentam and resistant starch.
Journal of Dietary Supplements, In press.
3. Andrresen V, Montori VM, Keller J, et al, (2008). Effects of 5- hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation m nonconstipated uritable bowel syndrome: a systematic review and meta-analysis of randomized eonttoiled ttials. Clinical Gastroenterology and Hepalology, Vol. 6, pp: 545.
4. OECD (2011), Repead dose 90 - day oral toxicity stady m rodents (OECD TG 408), OECD Guideline for The Testing of Chemicals.
