• N g h i e n CLFU - Ky t h u a t 7. 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.
8 S. i. Haider, Validation standard operating proceduces a step-by-step guide for achieving compliance in the pharmaceutical, medical devide, and biotech industnes, ST". Lucie Press (2006).
9. S. 1. Haider, Pharmaceutical master validation plan: the ultimate guide to FDA, GivlP and GLP compliance, ST. Lucie Press. (2002).
10. T. Comoglu et al., Development and in vitro evaluation of pantoprazole-loaded micropheres. Drug De/.(2008), 15, p. 295-298
11. WHO, WHO good manufactunng practices:
main principles for pharmaceutical products. (2011),
Nghien cij-u anh hu-oiig ciia bai thuoc thap vi giang dirong phu-cng len chirc nang
gan, than tren tho thuc nghiem
Tieu Ngpc Chien', Nguyen Trpng T^l6ng^ Pliam Thj Van Anh^
' Trung tarn Y ti Thanh Tri - Ha Not
^ Bo mon Duac ly - Tnr&ng dai hgc Y Hd Noi
Dat van de
B&nh ddi thao du-dng (£)TD) ngay mpt gia tdng, ca d cac nu-dc phdt tnen va dang phdt trien, chiem td-i 60-70% trong cac benh npi tilt, bpnh dang tang nhanh theo mire dp dinh du-dng ngdy cang cao. Benh ddi thdo du-dng Id nguyen nhan gdy tu- vong dirng hang thi> 4 a cac nu-dc phdt trien v d du-pc xem la nguyen nhdn gay benh tu- vong cao d cac nu-dc dang phdt triln'^'.
Cao Idng thap vj gidng du-dng phu-ang cd n g u i n g l c tir bdi thuoc thap v| giang duxi-ng phu-ang (TVGDP) du-pc bpnh vipn YHCT Ha Ddng u-ng dung vdo dieu trj tren lam sdng va bu-dc dau cd tdc dung hg du-dng huyet. Be nghien ciru tinh an todn ciia cao Idng thap vi giang du-dng phuxj-ng, Chung tdi t i l n hdnh nghien ciru d l tdi ndy vdi myc tieu: Danh gid dnh hi^cmg cua cao Idng th$p vi giang du^g phuvng len chuv ndng gan, th$n tren tho thu-c nghipm.
Doi tu'o'ng va phu-ang phap nghien CLPU
D o i tiFOPng v a c h i t li#u nghien cu-u Cdng thu-c bdi thuoc; sa sam: 16g, hodi s a n : 20g, thuc dja: 20g, k f tir: 20g, dan sam: 30g, thien hoa phan: 16g, ich tri nhdn: 15g, k h i l m thy-c 20g, tri mdu: 05g, tho phuc linh: 30g.
Thang thuoc gom 10 vj, mdt thang thuoc cd 192 g du-p-c lidu khd, l i l u trung binh: 1 thang/ngdy.
Hod chat
Kit djnh lu-png cac enzym vd chat chuyen hod trong mdu cua hang Hospitex Diagnostics (Italy) vd hang DIALAB GmbH (Ao), djnh lu-ang tren may Screen Master cua hang Hospitex Diagnostics (Italy).
Dgng vat thuv nghiem
Thd Chung New/zealand White, cd hai giong, khoe mgnh, long trdng, trong lu-ang 2,0-2,5 kg, tmng tdm chan nudi Vien K i l m nghiem cung cap.
Phu-cng phap nghien c i r u
Thd du-p-c chia ldm 3 Id, m5i Id 10 con, moi con n h I t rifeng mpt chuong.
- Ld chirng: uong nu-dc cat 2ml/kg/ngay.
- Ld tri 1: u l n g cao Idng TVGDP lieu 11,52 g/kg/ngdy {liiu co tac dung turyng dirong lieu dung tren nguui, tinh theo /jp so 3)
- Lo trj 2: u i n g cao long TVGDP lieu 34,56 g/kg/ngdy (gip 3 ian Id trj 1)
Thd du-pc uong nuxi-c hoac thulc thCr trong 12 t u l n lien, moi ngay mdt Ian vao b u l l sdng. Sau 12 t u i n uong thuoc, thd 6imc ngirng u I n g thuoc.
Cdc chi tieu theo ddi du-pc k i l m tra vdo tru-dc luc uong t h u l c , sau 4 t u i n , 8 t u l n va 12 tuan uong thuoc:
- Danh gid chu-c nang gan thdng qua dinh lu-p-ng hoat dO mpt sd enzym vd chat chuyen hod trong mau: ALT, AST, bilimbin toan phan.
T-^P CHi Dirge H Q C - 04/2012 (S6 432 NAM S2)
• Nghien CLPU - Ky thuat
albumin vd cholesterol.
- Ddnh gid chirc ndng th$n thdng qua djnh lu-png creatinin huylt thanh.
Xu- ly s i li^u
Cdc s i lipu nghifin ciru du-pc xir ly thing ke theo phu-ang phdp t-test student vd test "tru-dc -
sau"(Avant - Apr6s). Sy khdc bi$t cd ^ nghTa khi p<0,05.
K i t quci n g h i e n CLPU Ddnh gia chii-c nang gan
Kit qud nghidn ciru du-pc t h i hi$n qua cdc bdng 1-5.
Bang 1: Anh hu^ng cua th$p vj gidng dw&ng phuvng din ho^t dQ AST trong mdu thd
Tn/dc u6ng thu6c Sau 4 tu^n u6ng thudc
p {Imitc - sau) Sau 8 tuSn u6nq thu6c
p (tru'&c - sau) Sau 12tu^nu6ng thu6c
p (tn^dc - sau) Bang 2: Anh hu-d'ng cua
iRf&c uong thu6c Sau 4 \uin u6ng thu6c
p (tnjdc - sau) Sau 8 tuan uong thuoc
p (tri^6c - sau) Sau 12 tuan uong thuoc
p (truoc - sau)
L6 chipng 40,09 ±5,32 42,55*4,21
>0,05 39,01 t 5,62
>0,05 37.04 1 8.75
>0,05
Hoft di AST fUl/i) Li Irl 1 35.68 ± 5,84 43.34 ± 5,64
>0.05 37,57 ± 7,82
>0.05 41,50 ± 5,60
>0,05
L6 tri 2 44,45 ± 9.04 42.33 ± 4,74
>0,05 40,30 t 4,70
>0,05 38,73 t 7.92
>0,05
P ft. test Student
>0.05
>0,05
>0.05
>0.05 th$p vt giing tju^ng phuvng din ho^t dO ALT trong miu thd
L6 chieng 45,91 ± 5,55 49,56 ± 6,10
>0,05 45.49 ± 4,99
>0,05 48,92 ± 7,15
>0,05
HofI di ALT (Ul/i) L6 tri <
42,15 ± 6,24 54,55 ± 7,18
>0,05 44,97± 8,12
>0,05 46,52 ± 7,38
>0,05
L6tri2 50,19 ± 9,74 51,51t 6.35
>0,05 45,75 ± 7,02
>0,05 47,73 ± 5.95
>0,05
P (t- test Student)
>0,05
>0.05
>0,05
>0,05
Nhan xet: sau 4 tuln, 8 tuln vd 12 tuln uong thuoc lien tyc, cdc xdt nghiem danh gid chO-c ndng gan (hoat dp AST, ALT d ca Id tri 1 vd trj 2
Bang 3: Anh huvfng cua th$p vt gidng duxyng phuxyng din ndng dp albumin trong mdu thd khdng cd sy- khac bipt so vdi 15 chu-ng vd so vdi tru-dc u6ng thulc (p > 0,05).
_.. .
Tnritc uong thu6c Sau 4 tuln u6ng thu6c
p {Injf&c - sau) Sau 8 tuSn uong thu6c
p (trifle - sauj Sau 12tu^n u6ngthu6c
p (trucyc - sau) Bang 4: Anh hu^g ciia
ongtan
.
Tnrifc uong thu6c Sau 4 tu^n uong thuoc
p (tru^c - sau) Sau 8 tuln uong thuoc
p (tripac - sau) Sau 12 tuan uong thu6c
p (tru-ac - sau)
Lo chipng 5,70 ± 0,40 5,64 t 0,28
>0,05 5.92:( 0,16
>0,05 5,94*0,51
>0,05
Albumin (g/di) Lo tri 1 5,66 ± 0,31 5,52 ± 0,29
>0.05 5.94 ± 0.22
>0,05 5.99 t 0.55
>0,05 th^p VI gicing du^ng phuvng d4n nong
L6 chipng 2.05 ± 0,38 2,07 ± 0,21
>0,05 2.67 ± 0.91
>0,05 2.12 ± 0,71
>0,05
Cholesterol (mmoi/i}
Lo th 1 2,47 ± 0,49 2,14 ± 0,42
>0,05 2,18 ± 0,51
>0,05 1,99 ± 0,60
>0,05
L6tri2 5,83 ± 0,23 5,69 ± 0,25
>0,05 5.95 t 0.20
>0,05 6.05 ± 0,45
>0.05
P (t- test Student
>0.05
>0.05
>0,05
>0,05 d^ cholesterol trong mAu tho
L6 tri 2 2.48 ± 0.50 2,18 ± 0,24
>0,05 2.11 ± 0,40
>0,05 1.91 ± 0,53
>0.05
P (t- test Student)
>0,05
>0.05
>0,05
>0,05
TAP CHf Dirpc HQC - 04/2012 (SO 432 NAM 52)
• Nghien CCFU - Ky thuat
Bang 5: Anh hu6ng cua th$p vi giang duung phuxmg din nong do bilirubin todn phan tmng mdu thd Thdi gian Bilirubin tain phin (mmol/l)
Lo chirng L6 trj 1 (t- test Student)
Tru-dc uong thuoc Sau 4 tuan uong thuoc
p (tn^drc - sau) Sau 8 tuan uong thuoc
p (tru'oc - sau) Sau 12 tuln uong thu6c
p (truoc - sau)
12,11 ± 0,41
>0,05 12,22 ± 0,35
>0,05 12,34 ± 0,39
>0.05
12,36 ± 0.33
>0,05 12,25 ± 0,42
>0,05 12,17 t 0,34
>0.05
12,20 ± 0,37
>0,05 12,23 ± 0,22
>0,05 12.23 ± 0,40
>0.05
>0,05
>0.05
>0,05
Nhdn xet: Sau 4 t u l n , 8 tuan vd 12 tuan uong thuoc lien tyc. cac xdt nghiem nong dp albumin, cholesterol vd bilirubin todn p h I n trong mdu thd) d cd Id trj 1 vd trj 2 deu khdng cd sy-
khdc bi$t cd)/ nghTa thong ke so vdi Id chirng va so vdi tru-dc khi uong thuoc.
Danh gia chu-c nang than
Ket qud nghign cu-u du-pc the hipn qua bdng 6.
Bang 6: Anh hu^g cua th$p vi gidng duv'ng phux>ng dSn nong (?d creatinin trong mdu tho o i g a
.
Tnroc uong thuoc Sau 4 tuln uong thuoc
p (torac - sau) Sau 8 tuln uong thuoc
p (tnrac - sau) Sau 12 tuln uong thuoc
p {InrOc - sau)
Lo chipng 1,06 ± 0,05 1,04 ± 0,05
>0,05 1,04 ± 0,05
>0,05 1,06 ± 0,05
>0,05
Creatinin (mg/dl) L6 tri 1 1,05 ± 0,05 1,05 ± 0,05
>0.05 1,05 ± 0,05
>0,05 1,06 ± 0,05
>0,05
Lo tri 2 1,06 ± 0,05 1,06 ± 0,05
>0,05 1,06 ± 0,05
>0,05 1,05 ± 0,05
>0,05
P It- test Student)
>0,05
>0,05
>0,05
>0,05
Nhan xet Sau 4 tuan, 8 tuan, 12 t u l n uong t h u l c lien tuc, d- ca Id tri 1 vd trj 2 hdm lu-ang creatinin trong mau thd khdng cd su- thay doi khac biet so vai Id chu-ng vd so vdi tru-d-c khi uong thuoc.
B a n l u a n
Anh h u v n g cDa cao long thap vj giang dipffng den chu-c nang gan
Trong ca the gan id c a quan dam nhan nhieu chirc nang rat quan trpng. Khi du-a t h u l c vdo c a t h i cd the gdy ddc vdi gan, lam dnh hu-dng d i n chCi-c nang gan. Vi vdy, khi ddnh gia doc tinh cua thudc thi nghien ciru dnh hu-dng cua t h u l c doi vdi chu-c ndng gan id rat c i n thilt'^'.
De ddnh gid mu-c dp ton thu-ang te bdo gan, ngu-d-i ta thu-d-ng dinh lu-png hoat dp cac enzym cd nguon goc tgi gan cd trong huyet thanh'^^l Ket qua cho thay nong dp 2 enzym AST va ALT khdng tang trong h u y l t thanh d- ca hai thdi d i l m sau 4 tuan, 8 tuan vd 12 t u l n uong thuoc li§n tuc so vd-i id chu-ng va so vd-i tru-d-c u I n g thuoc, chirng td thuoc khdng gay t i n thu-ang te bdo gan cua thd.
TAP CHI DlTOC HOC - 04/2012 fS6 432 NAM 52)
C h u y i n hod cac chat npi sinh vd ngogi sinh la mpt trong nhu-ng chirc ndng quan trong cua gan. Gan cd mdt he thong cac enzym chuyen hoa rat phong phii cho qua trinh tong hpp vd thodi hod protein, lipid...'^•*'.
Tgi gan, cdc acid amin da du-pc tong hpp thdnh albumin, mpt sd globulin, mpt so yeu t l ddng mdu. Djnh lu-ang albumin trong mdu se ddnh gid du-pc mOt phan chirc nang c h u y i n hoa protein cua gan. Ngodi chuyen hod protein gan cdn cd chirc nang chuyin hod lipid. Cholesterol Id mdt thdnh p h I n cua mdt, du-ac gan t i n g hap, ester hod va thai ra ngoai'^'. Vi vdy, cd the diing xet nghipm djnh lu-png cholesterol de ddnh gia chu-c nang chuyen hod lipid cua gan. Trong nghien cu-u, hdm lu-ang albumin vd cholesterol trong mdu cua thd d hai Id trj khdng thay doi sau 4 tuan, 8 tuan vd 12 tuan diing t h u l c so vdi tru-dc dung thuoc. Chii-ng td khd nang c h u y i n hod protein vd lipid cua gan khdng bj anh hu-dng khi uong cao Idng thap vj gidng du-dng phu-ang
Mpt chu-c nang quan trpng cua gan phdi ke den la chCrc nang t i l t mgt. Gan tgo ra mgt, bai 17