e Quan ly - Trao doi
Tham tach micro, kl thuat dmh luccng thuoc dang tu' do tai mo dich tac dung: Nguyen t k
va ling dung trong nghien ciru thuoc
'Lah Dirac Iv phan lir
D a t v a n de
Hien nay h l u h i t cac thulc dyac danh gia tac dung du'oc iy thong qua viec dmh lu'ong tong nong do thuoc (ca dang tu' do va dang gan k i t voi protein) co trong mau Tuy nhien, da s6 cac thuoc CO tac dung du'oc iy lai deu a dang ty do va tac dung do lai dien ra a cac mo dich tac dung cua thuoc (Targeted Drug Tissues), chy khong phai trong mau Vi vay. danh gia du'oc ly cua mot s i thuoc thong qua dmh lyang nlng do thulc o dang t y do tai mo dich tac dung cua thuoc dyoc xem nhy la mot each hop ly nhit d l cung d p cac diy lieu iam sang co y nghTa hon cac k i t qua thu dyac ty trong mau '^' Hien nay, cac ky thuat nano du'O'c ap dung ngay mot nhieu trong cong nghe bao che d l tao ra cac thulc giai phong hoat c h i t tai dich tac dung (Targeted Drug Delivery) '•*', do do viec xac dmh nong do thulc tai mo dich se la yeu t l thuan loi cho cong nghe nay phat tnen Bai tom t i t nay nham mo la ky thuat tham tach micro va mot so ij'ng dung cua no trong nghien cu'u thuoc Tu' do, hy vong trong tu'ong lai khong xa, dmh luong cac thulc dang ty do tai cac mo dich tac dung, co the tro thanh tieu c h u i n hang d§u trong viec danh gia tac dung duoc iy cCia thuoc
Nguyen tac cua ky thuat tham tach micro
Tham tach micro la kl thuat cho phep xac dmh duoc nong do cac chat noi sinh va ngoai sinh tai mo dich tac dung, dya vao sy khuech tan thu dong cua cac phan t y co trong iu'ang t h i p khi qua cac 16 CLia mot mang ban tham (hinh 2) tren mot kim tham do dyac cay vao t l chuc dich
Cac chat noi sinh 6* day g o m : Cac c h i t d i n truyen than kinh nhu' serotonin, noradrenalm hay dopamin. phan tLi' d y o n g , insulin, cac hormon noi t i l t
Nguyen T h a n h H a i , G i i i a r d Bruno , G a r i l i c r A l a i n " , T h a i N ^ u j c u H i i u g T h u '
Tnrdiigilcji lioc Diro'c Ha \'oi. I'lcl .\aiii
•} than kiiih. Tniuiigitai hoc Pari.\ 11. CI I Phap
Cac chh ngoai s i n h : dien hinh la cac phan t y thulc
Hinh 2: Su khuech tan thu dong cua cac phan tu' CO trong liiong thip khi di qua cSc Id cua mang ban thim tai cac mo dich tac dunff T A [ * C H i D L J O C H O C - 0 I / 2 0 I 2 ( S 6 4 2 9 N \ M 5 2 )
O Q u a n ly - T r a o dor
Nhu'ng y u diem cua kl thuat tham tach micro - Xac dmh d y a c nong do cac phan t y thulc 6 dang t y do, 6 dang nay thulc moi co tac dung va CO m i l tyong quan thuan voi hieu qua dieu tn
- Xac dmh d u o c n l n g do cac phan ti> t h u l c tai cac mo dich tac dung cua t h u l c
- D i l u tn tai mo dich, noi ma cac phan tij' thulc khong t h i phan b l d i n cac mo benh Dya vao kha nang khulch tan qua mang ban thIm, ngyai ta CO t h i pha dung dich chira thulc, roi truyin vao qua kim tham do duoc cay tai mo dich, cac phan tu' thuoc se khuech tan vao mo benh
Mac du ky thuat thIm tach micro co nhieu thuan loi. tuy nhien van con co mot so gioi han nhy
- Nlng do thuoc co trong dich thu d y a c r i t nho, nen c I n phai st> dung thiet bi phan tich co do nhay rIt cao nhy sac ky long hieu nang cao VO'I detector dien hoa hay huynh quang
- Khoi luong phan tu' cua cac thuoc khong vu'ot qua 50 kD
- Kha nang chon loc cac phan t y thulc khong cao, do ky thuat thSm tach qua cac 16 mang ban thIm nen cac phan ti> khac nhy cac c h i t chuyin hoa cua thulc, cac chat noi sinh co trong lyang phan tiJ- nho cung c6 t h i qua du'oc
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Hinh 3: Nguyen tic hoat dong cua mot kim tham do duuc ciy vao mo dich tac dung cua thudc Mot quy trinh chung cho nghien c y u thuoc co SU' dung kl thuat tham tach micro bao gom 5 bu'oc (cho ca cac nghien cu'U t i l n lam sang Ian nghien cu'u lam sang)
1 Chuan bi cac kim tham do, dung dich truyen co thanh p h i n va nong do tu'ong u'ng vo'i dich tai m6 dich can nghien c y u va cac d l i tu'ong nghien cu'u
2 Cay kim tham do vao m6 dich tac dung cua t h u l c
3 T r u y i n dich co thanh p h I n va n l n g do tyong yng vo'i dich tai mo dich tac dung vai toe do rIt Cham (tu 0,1-5|.il/phLit), dich thu d u o c se CO chya cac phan ty thuoc
4 Dmh iuang n l n g do phan t y thuoc trong dich thu dyoc b§ng phu'ong phap s i c ky long hieu nang cao (HPLC)
5 Hieu chinh lai nong do thulc thong qua hieu suat in vitro hoac in vivo cua mang ban tham 86'! vi kT thuat t h I m tach micro dya vao s y khulch tan cac phan t y thuoc qua mang ban tham theo gradient n l n g do, do do n l n g do thuoc thu d y o c chya phan anh d y o c n l n g do that tai m6 dich nen c I n hieu chinh lai theo hieu suat CLia mang ban t h I m qua nhyng nghien cuu in vitro hoac in vivo '^'
U'ng dung ky t h u a t tham tach micro trong nghien CLPU thuoc
Tham tach micro d y o c biet den t y nhu'ng thap men 1960 khi su dung mot ttji tham tach co kich thyac 16 mang rIt lo'n d l thu d y a c cac phan ti> acid amin trong cac t l chU'c m6 tren dong vat thyc nghiem''' D i n nam 1974, nha s y h i tra CLia cac phu'ong phap dinh lyang mo'i, Ungerstedt va cong sy'^' da cai tien lai kT thuat du'O'i dang kim tham do cO dau la mang ban t h I m va dya ra cong trinh nghien cu'u d I u tien v l dmh iu'ong n l n g do dopamin trong nao chuot thyc nghiem. Nam 1987, kT thuat nay d y o c ap dung nghien cyu dmh lyong phan ttj' glucose trong dich ke te bao tren ngyoi tinh nguyen '^' T y do den nay kT thuat tham tach micro cang d y o c cai tien va co nhieu nghien cu'u yng dung quan trong trong khoa hoc Y D y o c tren the gioi, dac biet trong nghien c y u thuoc Cac nhom t h u l c dang du'oc nghien cu'u ap dung nhy thuoc c h i n g ung thy, thuoc khang sinh hay thuoc chong t r i m cam
T h u l c chong ung thiF co tac dung h y a n g dich
Chi nhu'ng nam gan day, khi ma cong nghe bao c h i nano phat tnen de tao ra cac thulc co tac dung hyo'ng dich, dac biet ia cac nhom t h u l c chIng ung thy, n g y o i ta bat dau ngh]
n h i l u d i n nghien cu'u si> dung kT thuat tham tach micro trong viec xac dmh n l n g do t h u l c chong ung thy tai cac mo dich tac dung ciJa
I M'CHJ I)1]OCHOC-01/20I2(S()42') NAM 52)
O Quan ly - T r a o d o i
thuoc (mo ung thy). Cac nghien cuu tru'oc day da chyng minh nong do t h u l c tai mo ung thy ty le thuan voi hieu qua dap yng tren lam sang cua benh nhan'''' Vi vay viec yng dung kT thuat tham tach micro cho phep xac dmh n l n g do thulc chIng ung thy tai cac mo dich la y l u t l thuan loi giup cho cong nghe nay phat tnen
Kha nang phan bo vao cac mo cua thuoc khang sinh
Hau h i t cac I nhiem trung d I u n l m a cac mo ngoai vi hoac cac t l chyc ciJa co the nhy p h l i tai mui hong, da, nieu quan, dich ke mo ma rat it xay ra tai ngan trung tam (he t u i n hoan mau) Vi vay lu'a chon mot khang sinh de dieu tn cho benh nhan nhIt thiet phai biet thuoc do co kha nang phan b l d i n cac mo nhilm trung hay khong, chi co nong do khang sinh 6' dang t y do trong dich ke mo tai I n h i l m trung moi co kha nang mang lai hieu qua dieu tn khang khuan '^' KT thuat tham tach micro cho phep xac dmh n6ng d6 thulc a dang t y do (dang t h u l c co tac dung) tai cac mo dich tac dung cua thuoc (noi xay ra cac I nhilm trung) Do do, kT thuat nay CO t h i giup cac nha nghien cii'u va nha dieu tn hoc sang loc va phan loai cac t h u l c khang smh theo kha nang phan b l d i n cac mo nhilm trung, nang cao hieu qua d i l u tn cho benh nhan
Dac tinh d y o c ly va c o che tac dung thuoc chong tram cam
Mot trong nhCrng nguyen nhan gay ra benh tram cam du'oc bilt den nhieu nhIt la giam nong do cac c h i t dan truyen t h i n kinh tai synap cua te bao than kinh Vi vay, t i t ca cac t h u l c chong t r i m cam ngay nay deu co chung mot tac
dung lam tang n6ng do cac chat d i n truyin t h i n kinh trong cac vung nao, trong do quan trong nhat la serotonin. D l nghien ci>u hieu qua, cung nhy CO che tac dung ctJa cac thulc chIng trim cam, chi c I n thong qua xac dmh n l n g do cac c h i t d i n truyen tai cac khe synap cua t l bao t h i n kinh'^' Ti> do, t h I m tach micro la mot kT thuat u'u the nhat co kha nang xac dmh nlng do cac c h i t d i n truyen t h i n kinh tai cac khe synap ctJa t l bao than kinh trong cac vung nao tren dong vat thyc nghiem v i n hoat dong binh thyo'ng
Summary
Microdialysis Is a new method for studies of drugs in animals and man
Tai lieu tham khao
1 Bito L. Davson H, Levin E M. Murray M and Snider N , The concentration of free ammo acids and other electrolytes in cerebrospinal fluid, in vivo dialysate of brain and blood plasma of the dog, J.Neurocfiem (1966). 13(11). 1057-1067 2 Chaurasia C S . Muller M., Bashaw E D , Ungerstedt U , et al AAPS-FDA Workshop Wtiite Paper Microdialysis Principles, Application and Regulatory Perspectives Phann Res (2007), 24 (5), 1014- 1025.
3 Muller M Science, medicme, and the future Microdialysis BMJ (2002), 324(7337), 588 - 591
4 Muller M. Mader RM, Steiner B, Steger GG, Jansen B, Gnant M S-Fluorouracil kinetics in the interstitial tumor space clinical response in breast cancer patients Cancer Res (1997), 57, 2598 - 2601
5 Ungerstedt U "Microdialysis—principles and applications for studies in animals and man", J Intern Med (1991), 230,365-373.
T a c d u n g c h o n g . . . (Ti4p theo trang 55)
Summary
7/76 experiments for testing anti-inflammatory and anti-diarrhea effects of the traditional decoction named Huangqin decoction was done The results show that, with the dose at 2.2 g / kgBW and 4 4 g / KgBW white mice, Huangqin tang has anti-inflammation and anti-diarrhea effects (p <0 01} At high doses of 8 8 g4<gBW white mice Huangqin decoction still has good anti- dianhea effect (p <0 01). but did not show anti- inflammation with statistically significant
Tai lieu tham khao
1 Tru'ong Trong Canh, Thu'ong han lu$n, Nha xuit ban Ve sinh nhan dan (Tiing Trung), (1963)2 Tai'ong Ban, Phan tich va giang nghTa thu'O'ng han luan, NXB Nhan dan Noi Mong (Tiing Trung), (1987)
3 Iran Ky, PhLvang phap nghien cu'u tac dung du'OC ly trung du'oc, Nha xuat ban Ve sinh nhan dan.
trang 647 (Tieng Trung), (1993)
4 Ta Minh, Phucng te hoc, Nha xuat ban ve sinh nhan dan (Tiing Trung), (2003)
5 LIU Gongwang, Fundamentals of Formulas of Chinese Medicine, Huaxia Publishing House (2007)'
TAP CHi DUOC HOC - 01/2012 (SO 429 NAM 52)
