Therapeutic oligo- and polysaccharides
© Oldřich Farsa 2012
chondroitine sulfate
poly--D-glucurono-(13)-2-deoxy-2-(acetylamino)--D-galactopyranose
polysulfafe
●prepared by hydrolysis of porcine, bovine or shark cartilages; the composition of
the mixture markedly depends on the both raw material and preparation
procedure
●absorbed in small intestine in the amount < 10 % probably by an endocytose
mechanism
●acts as a prebiotic in the distal part of GIT and is degraded by enzymes of the
intestinal microflora into na mono- and disaccharides that are peptidoglycane
precursors (namely N-acetylgalaktosamine)
●recommended daily dose 800 mg
Authorized drug preparations: Condrosulf ®
Nutraceutics: Mobilin ® , Artryn ® , Gelactiv ® , GS-CS-MSM 3000 ® , GS-Condro
(forte) ®, Proenzi 3 ® , Proenzi premium forte 3000 ® -combined with
glucosamine and sometimes also with MSM
Therapeutics of arthrosis and arthritis
OR
OH
O
O
OH
O
NH
OR
O
OR
O
CH3
O
O
*
*
n
R = -H nebo -SO2OR
= H or -SO2
O-
Anticoagulants
Heparines
High-molecular mass heparines
O
H
H
H
H
O
OH
H OH
O
O
-
O
O
O
H
H
H
OH
H NH
H
OH
S
O
- O
O
O
H
H
H
H
OH
H O
OO
-
O
S
O
O
O
-
O
O
H
H
OH
OH
H NH
H
O
S
O
O
O
-
S
O
O
O
b-D-glucuronic
acid (a-D-galactosamine) (a-L-iduronic acid) (a-D-glucosamine)
Heparine chain fragment
●6 000 < Mr
< 20 000
●< 30 % glucuronic acid
●< 70 % iduronic acid
●
Heparinum natricum, Heparinum calcicum EP; Heparin Forte Léčiva
●Mode of action: activates 2
-globuline antitrombin (AT III); heparin-antitrombin complex
blocks then blood clotting factors and avoids thrombine formation
●acts as an „superficial catalyser“
●5 saccharide units suffices for binding to AT III, binding of additional units stabilizes this
complex
●isolated from bovine lungs or from intestinal mucous membranes of cattle, pigs or sheep
Antikoagulants
Heparines
Low molecular mass heparines
●EP: a common article Heparina massae molecularis minoris
O
H
H
H
OH
OH
H O
O
H
O
-
O
O
O
H
H
H
OH
H NH
H
O
S
O
-
O
O
R
1
R
2
O
H
H
R
4
H
OH
H OH
O
R
3
O OH
H
OHH
H
OH
O
S
O
OO
-
Na
+
Na
+
Na
+
n
dalteparine sodium salt
Dalteparinum natricum EP
2 < n < 21, R1
= H or SO3
Na, R2
= SO3
Na or COCH3
; R3
= H and R4
= COONa or R3
=
COONa and R4
= H
Fragmin
inj. sol. (s.c.)
●treatment of deep venous thromboses and lung embolisms; prevention of blood clotting in an
out-of-body system in haemodialysis and haemofiltration linked with an accute renal failure or
a chronic renal insufficinecy; prophylaxis of thromboembolism linked with a surgical
interventions; treatment of an unstable angina pectoris and non-Q myocardial infarction
O
H
H
H
OH
OH
H O
O
H
O
-
O
O
O
H
H
H
O
H NH
H
O
S
O
-
O
O
R
1
R
2
O
H
H
R
4
H
OH
H O
O
R
3
O OH
H
OHH
H
OH
O
S
O
OO
-
R
1
R
1
n
3/2 Ca
2+
nadroparine calcium salt
Nadroparinum natricum EP
R1
= H or SO3
(1/2Ca), R2
= H or SO3
(1/2Ca) or COCH3
R3
= H and R4
= COO(1/2Ca) or R3
= COO(1/2Ca) and R4
= H
Fraxiparin multi
inj. sol.
Na
+
Na
+
Na
+
n
O
S
O
OO
-
O
H
H
H
OH
OH
H O
O
H
O
-
O
O
O
H
H
H
OH
H NH
H
O
S
O
-
O
O
R
1
R
2
O
H
H
R
4
H
OH
H OH
O
R
3
O
H
H
H
H
OH
H NH
OH
S
O
-
O
O
Na
+
parnaparine sodium salt
Parnaparinum natricum EP
0 < n < 22, R1
= H or SO3
Na, R2
= SO3
Na or COCH3
R3
= H and R4
= COONa or R3
=
COONa and R4
= H
Fluxum
inj. sol.P
tinzaparine sodium salt
Tinzaparinum natricum EP
0 < n < 26, R1
= H or SO3
Na, R2
= H or SO3
Na or COCH3
, R3
= H and R4
= COONa or
R3
= COONa and R4
= H
Na
+
Na
+
Na
+
n
O
S
O
OO
-
O
H
H
H
OH
H O
O
O
-
O
O
O
H
H
H
OH
H NH
H
O
S
O
-
O
O
R
1
R
2
O
H
H
R
4
H
OH
H O
O
R
3
O
H
H
H
H
OH
H NH
OH
S
O
-
O
O
R
1
Na
+
Synthetic short chain heparinoids
fondaparinux sodium
Arixtra®
●s.c.
●prophylaxis of deep venous thrombosis after fractures, surgical interventions etc.
S
O
O
-
O
H
HH
H
H
O
O
CH3
NH
S
O
O
O
-
OH
O
H
O
H
O
- O
H
H
HO
S
O
O
-
O
OH
O
H
H
H
O S
O
O
-
O
H
H
O
O
S
O
O
- O
O
H
O
H
H
HH
OH OH
O
H
H
H
H
H
O
O
S
O
-
O
O
OH
OH
NH
S
O
O
O
-
O
-
O
NH
S
O
O
O
-
O
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Synthetic short chain heparinoids
idraparinux sodium
syn. SR 34006
●s.c. aplication once weekly only
●phase 3 clinical study for deep venous thrombosis or symptomatic lung embolism
O
S
O
O
O
-
H
HO
CH3
H
H
H
O
H
H
O CH3H
H
O
H
H
O
H
O
H
H
O
H
O
HH
H
H
O
H
O
S
O
O
-
O
O
CH3
O
S
O
-
O
O
O
S
O
-O
O
H
H
O
CH3
O
CH3
O
- O
H
H
O S
O
O
-
OO
S
O
O
O
-
O
S
O
O
-
O
O
H O
-
O
O
CH3
O
O
CH3
O CH3
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Sulodexide
●a mixture containing 80 % of fast mobility heparine (FMH) and 20 % dermatan sulfate
●FMH fraction is described based on its electrophoretic mobility
●both fractions have lower degree of sulfation and lower anticoagulant activity compared to
unfractionized heparin
●obtained from the porcine intestinal mucosa by a patented process
●lower Mr
 extensive oral absorption  possibility of oral administration
●oral administration results in the release of tissue plasminogen activator and an increase
in fibrinolytic activities
●longer T1/2
●reduced effect on systemic clotting and bleeding
●treatment of various vascular pathologies including sudden death after MI prevention
●efficiency in treatment of deep vein thrombosis, venous leg ulcers and reduction of
reperfusion injury after MI demonstrated by clinical trials
●Vessel Due ® - used
●Sulonex ® - phase 3 and 4 clinical tests for diabetic neuropathy
O
H
H
H
O
H
H
NHCH3
O
OH
OH
O
S
O
O
O
-
H
O
H
H
OH
H
H
OH
OH
OO
-
n
dermatan sulfate