I HC DC H NI

B MN HA DC

CC THUC IU TR
I THO NG
GVHD: Th Mai Dung
Nhm thc hin : T 4- A6K67

NI DUNG
I

S lc lch s nghin cu v pht trin cc thuc T.

Phn loi cc thuc T.

II

Lch s pht trin, CTCT, TD, C, TDKMM ca nhm

sulfonylurea.
Cc thuc nhm sulfonylurea.

III

Kim nghim 1 thuc i din ca nhm sulfonylurea:

Glibenclazid.

Bnh i Tho ng
nh ngha:
T l mt bnh mn tnh gy ra bi s thiu ht
tng i hay tuyt i insulin ,dn n ri lon chuyn
ha Hydrat cacbon,c trng bi s tng ng huyt
mn tnh v cc RLCH khc.

Mc tiu iu tr: H ng huyt

I. S lc lch s nghin cu thuc iu tr

T
1. Lch s nghin cu:
- Nm 1922 , ln u tin
Banting v Best tch c
insulin t tuyn ty ca ch v
a vo iu tr.
- Nm 1942, Janbond v ng nghip
pht hin mt s sulfamid c TD h
ng huyt => a carbutamid vo
iu tr T nhng hi ty xng=>
khng dng .
- Nm 1950, tolutamid c s dng
rng ri trong iu tr bnh T.
=>20 h/c thuc nhm sulfonylure
c a vo iu tr .

- u TK 20, pht hin guanidin trong cy

Galega officinale c TD h ng huyt nhng
c.
=> Khng dng iu tr.
- 1 biguamid u tin- phenformin c dng trong LS
nhng gy nhim acid lactic=> khng dng.
- 1 biguamid khc- Metformin(1957) c TD tt, t TD
ph
=> s dng hin nay.
- Nhm thiazolidinedion :
+ Troglitazol l cht u tin nhng c gan => cm dng.
+Pioglitazone v rosiglitazon an ton v c dng ( 1999).
+2007,pht hin rosiglitazon lm tng nguy c nhi mu c
tim v t vong do tim mch.=>cm dng

2. Phn loi
Theo c ch tc dng c chia thnh 7 nhm:
o Insulin.
o Nhm kch thch bi tit insulin: sulfonyurea, meglitinid.
o Nhm lm tng s nhy cm ca t bo vi insulin: biguanid,
thiazolidindion.
o Nhm lm chm s hp thu carbonhydrat rut: cc cht c ch
-glucosidase.
o Nhm c tc dng ging incretin hoc ko di tc dng ca
incretin: incretin mimetic v cc thuc c ch DPP-4 (dipeptidyl
peptidase-4).
o Nhm c ch SGLT2 (Sodium-glucose transporter 2).
o Thuc pramlintid: h glucose mu bng cch c ch glucagon v
lm chm qu trnh rng d dy.

II. NHM SULFONYIURE

1. Lch s nghin cu:
+ Nm 1942, BS Marcel Janbon pht hin 1 loi khng sinh sulfamid(VK
57) c nhiu tc dng ngoi .
+ T 1942-1946 ,Loubatieres nghin cu c ch TD ca VK57 , Vk57 l
nhm thuc u tin iu tr mt s dng c bit ca T v c th dng
ng ung.
+ Nm 1966, th h th 1 ca SU ra i vi chlorpropamide, tolbutamide,
tolaza- mide v acetohexamide nhng c nhiu nhc im => b hn ch s
dng.
+ Nm 1972, nhng thuc u tin ca th h th 2 ra i vi
glibenclamide( glyburide), glipizide, gliclazide v glimepiride.
=> hon ho hn v khc phc gn nh trit bt li ca th h u,
c bit 2 thuc: glimepride v gliclazide .

Cc thuc trong nhm:

Sulfonylur
e
Th h 1
-Tolbutamid
-Clopropamid
-Tolazamid

Th h 2
- Glyburide
(glibenclamid)
- Glipizid
- Gliclazid

Cng thc cu to chung

Lin quan cu trcTD
- Thn du mch
thng 3C-6C =>
TD ti a
- Vng thm: hp
cht c

nh hng n
thi gian tc dng

H linh ng: tnh

acid yu=> lin kt
mnh vi protein
mu

2. Tnh cht l, ha
a, Tnh cht vt l:
o Bt kt tinh trng
hoc hu nh trng
o Kh tan trong nc,
d tan trong
mt s dung mi hu
c
o Nhit nng chy
xc nh.
o Hp th UV , IR

b, Tnh cht ha hc
o Ha tnh ca nhn
benzen : hp th UV
o Ha tnh ca nhm
chc sulfunylure :
- Tnh acid yu
- D b thy
phn trong mi trng
kim
- Acid ha gii
phng kh carbonic

3. Tc dng v c ch tc
dng
a, C ch tc dng

Tc dng da trn 2 c ch c bn:

Kch thch gii phng insulin t cc t
bo beta o ty cn hot ng.
Tng hiu lc ca insulin ni sinh v
ngoi sinh.
Ngoi ra:
Tng nhy cm ca t bo beta vi
cc cht kch thch tit insulin khc
Tng nhy cm ca m ch vi
insulin .
Kch thch gii phng somatostatin- cht
c ch gii phng glucose.

H glucose

b, Tc dng khng mong mun

- H ng huyt qu mc.
- Ri lon tiu ha: nn, bun nn, vng da, tc mt
- D ng.
- Tan mu.
- Thoi ha bch cu ht.
- Phn ng ging disulfuram khi dng clopropamid cng
vi ru(10-15% BN)
- H natri mu, d gp vi clopropamid do c tc dng
ging ADH gp 50% BN.

III. Kim Nghim(Glibenclamid)

Glibenclamid

C23H28ClN3O5S

PTL: 494,0

1-[[4-[2-[(5-Cloro-2-methoxybenzoyl)amino]ethyl]phenyl]sulphonyl]-3cyclohexylure
Phi cha t 99,0 n 101,0% C23H28ClN3O5S, tnh theo ch phm khan.

1. nh Tnh
C th chn mt trong hai nhm nh tnh sau:
Nhm I: A, C.
Nhm II: A, B, D, E.
A. im chy:
- T 169 oC n 174 oC
B. o hp th:
-Ha tan 50,0 mg cp + CH3OH(TT) => 50 ,0 ml dd A.
- Ly 10,0 ml dd A + 1,0 ml dd HCL 10,3 %( kl/tt) +
CH3OH(TT)=> 100,0 ml dd B.
- o hp th ca dd B trong khong 230- 350 nm.
max= 300 nm vi A( 1%,1 cm)= 61-65.
max=275 nm vi A ( 1%,1 cm) =27-32.
C. Ph hng ngoi IR ca ch phm phi ph hp vi ph hng
ngoi ca glibenclamid chun (C).

D. Phng php sc k lp mng

- Bn mng: Silica gel GF254 (TT).
- DM khai trin: Ethanol 96% - acid acetic bng - cyclohexan methylen clorid (5 : 5 : 45 : 45).
- Dd th: 10 mg cp +10 ml hh methanol-methylen clorid(1:1) =>10 ml
dd th
- Dd i chiu: 10 mg glibenclamid chun (C) +10 ml hh methanol
(TT) - methylen clorid (TT) (1:1) =>10 ml chun.
- Yu cu: Vt chnh thu c trn SK ca dd th phi ging v v tr
v kch thc vi vt chnh thu c trn SK ca dd i chiu.
E. Phn ng ha hc:
- 20 mg cp+ 2 ml H2SO4 (TT)=> dd khng mu => Soi UV 365nm c
HQ xanh lam .
- Dd + 0,1 g cloral hydrat(TT)=> lc tan,sau 5p c dd vng m,sau 20p
dd mu nu nh.

2.

Th gii hn

Phng php sc k lng :

Dd th: 5,0 mg cp + methanol (TT) =>10,0 ml vi cng dung mi .
Dd i chiu (1): 5,0 mg tp cht chun A ca glibenclamid (C) + 5,0 mg
tp cht chun B ca glibenclamid (C) trong methanol (TT) thnh 100,0
ml vi cng dung mi.
- Pha long 5,0 ml dung dch ny thnh 20,0 ml vi methanol (TT).
Dd i chiu (2):
- 2,0 ml dd + methanol => 100,0 ml vi methanol (TT).
- Pha long 5,0 ml dd ny thnh 50,0 ml vi methanol (TT)
Dd i chiu (3):
-5 mg gliclazid chun (C) +methanol (TT) + 2 ml dung dch th => 100
ml vi methanol (TT).
- Pha long 1 ml dung dch ny thnh 10 ml vi methanol (TT).

iu kin sc k:
- Ct thp khng g (10 cm x 4,6 mm) c nhi pha tnh C (3 m).
- Nhit ct: 35 oC.
- Pha ng:
+ Pha ng A: Trn 20 ml dung dch triethylamin (va mi
c ct li) 10,18% c iu chnh v pH 3,0 bng acid phosphoric
(TT) v 50 ml acetonitril (TT), pha long thnh 1000 ml vi nc.
+ Pha ng B: Pha ng A - nc - acetonitril (20 : 65 : 915).
- Tc dng: 0,8 ml/pht.
- Detector quang ph t ngoi t bc sng 230 nm.
- Th tch tim:10 l.

Kim loi nng

- Khng qu 20 phn triu.
Mt khi lng do lm kh
- Khng qu 1,0%
(1,000 g, 100 105 C).
Tro sulfat
- Khng c qu 0,1%
Dng 1,0 g ch phm.

3. nh lng
PP trung ha:
Nguyn tc: Glibenclazid c tnh acid yu ,tc dng
vi NaOH.
Cch tin hnh:
NaOH 0,1 M
Cx 0,4 g cp
100,0 ml
ethanol 96%

un nng
Tan ht

Dd sau un
Ch th
phenolphtalein

Chun n khi ch th chuyn hng th

dng.
- 1 ml NaOH 0,1 M ~ 49,40 mg C23H28ClN3O5S.
-

Xin chn thnh

cm n c v cc
bn theo di !

Danh sch sinh vin T 4A6K7

1.
2.
3.
4.
5.
6.
7.
8.

Vi Th Thm
V nh i
Nguyn Vn Chung
Nguyn Thy Hng
Nguyn Th Hin
Hong Th Linh
Chu Qunh Mai
Nguyn c
Nguyn

9. Hong Hng Tho

10. Phng Phng Tho
11. Phm Vn Thng
12. Trn Th Thm
13. Bi Thu Trang
14. on c Vit
15. Vng Th Xanh