| Composition: |
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Hepaticum contains Silymarin
which is a natural complex
mixture of flavanolignans
obtained by extraction of
the ripe fruits of Milk Thistle
(Silybum marianum ).
It contains beside Silybin
(Silibinin), which is the
main active constituent, Iso–silybin
, Silychristin and Silydianin
A
Silybin–rich brand of
Silymarin, standardized to
a Silybin–content of
not less than 45% is used
in Hepaticum. |
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| Pharmacokinetics
: |
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After an oral dose, 20-50%
of the amount of Silybin is
absorbed. 80% of the drug
is excreted in bile(1).
About 10% undergo enterohepatic
circulation; after multiple
dosing, steady state blood
levels are reached in the
second day of treatment(2).
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The extent of absorption
is highly dependent on the
formulation of the dosage
form and can vary by a factor
of 2 between different preparations(3).
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In Hepaticum, Silymarin
absorption is enhanced by
micronization as well as by
inclusion in ß-cyclodextrin
as complex. |
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| Pharmacology |
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| Pharmacologic
studies carried out with the
isomeric mixture and with
the main component Silybin
revealed 2 main effects: |
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Antitoxic effects and enhancing
action on the regeneration
of liver tissues |
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The antihepatotoxic effect
is attributed to the binding
of Silymarin to the proteins
& receptors of the cell
membrane, substituting thus
the toxins and suppressing
their penetration into the
cells.(4) |
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The potentiating effect
on the regeneration is attributed
to the stimulation of protein
biosynthesis.(4) |
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The curative – therapeutic
action of Silymarin is attributed
to the stimulation of liver-cell
regeneration, specially by
the Silybin component(5). |
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Silybin
increases the total cellular
protein synthesis by the
following mechanism (6,7):
Silybin displaces a cell–own
regulator on a submit of
the RNA- polymerase of the
cell nucleus. This stimulates
the polymerase to an increased
and more rapid formation
of ribosomal RNA; the transcription
rate is increased.
A consequence of that is
the improved formation of
ribosomes and as a secondary
reaction, increased cellular
protein synthesis (5).
The regeneration –
potentiating action of silybin
is reached at concentrations
tenth of that required for
the membrane antitoxic effect.
The clinically observed enhancement
in liver cell regeneration
under the influence of silymarin
preparations is explained
by the regeneration potentiating
effect of silybin(8).
Silybin proved to be a strong
scavenger of hypochlorous
acid – and a strong
inhibitor of the formation
of leukotrienes via the 5-lipoxygenase
pathway. The deleterious effects
of HOCl, that can lead to
cell death, and those of Leukotrienes,
that are especially important
in inflammatory reactions,
can be inhibited by silybin
in concentrations that are
reached in–vivo after
the usual clinical dose (9,10).
The selective inhibition of
leukotriene formation by Kupffer
cells can, at least, partly
account for the hepatoprotective
properties of Silybin(10).
Silybin was shown to increase
both glutathione S-transferase
and quinone reductase activities
in liver, lung, stomach,
skin and small bowel. This
underlines the strong cancer
chemo-preventive effect
of silymarin, an effect
which was correlated to
the silybin component.(11)
Silymarin increases glutathione
production by the liver,
intestines & stomach(12).
Silybin decreases hepatic
& mitochondrial glutathione
oxidation induced by iron
overload and is a mild chelator
of iron.
At a dose of 140 mg t.d.s.,
Silymarin was shown to be
hepatoprotective, specially
in patients with alcoholic
cirrhosis and child’s
A group classification of
portal hypertension(13).
Silymarin 420 mg/day induced
a significant decrease of
S-SGPT & S-SGOT after
4 weeks. Histological changes
in the liver normalized
significantly more than
in the control group(14).
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Non-labeled indications:
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Cholestatic liver disease
and jaundice |
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Hyperbilirubinemia in the
newborns. |
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Post-cholecystectomy |
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Viral and drug-induced hepatitis. |
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Dosage :
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Adult
dose |
One
capsule 3 times daily
or, 10 ml. of the suspension
4 times Daily.
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Maintenance
dose |
One capsule
or 10 ml. of the suspension
twice daily.
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Pediatric
dose |
5 ml.
of the suspension 3
times daily, in serious
cases ,10 ml. of the
suspension 3 times daily.
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Infantile
dose |
5-10
mg/kg/day in 2-3 divided
doses.
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| Contraindications:
None.
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| Drug interactions
: None reported.
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| Adverse Reactions
: |
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A mild laxative effect may
be exerted occasionally as a result
of increased bile formation and
flow.
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| How Supplied: |
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Capsules (140mg) : Boxes
containing either 10 or 30
capsules each. Suspension
(50mg/5ml) : Bottles* containing
120 ml of suspension each.
* The bottle is to be
shaken before use.
|
References:
|
(1) |
Mennicke, 1975; German
Pharmaceutical J., 115,
1205 |
(2) |
Lorenz
et al , 1992; Planta
Medica, 45, 216 |
(3) |
Schulz
et al, 1995; Drug Research,
45, 61 |
(4) |
Reuter,
1992; in “Drug
Therapy Today”
, Aesopus, Basel |
(5) |
Sonnenblicher
& Zetl 1988; in
“Plant Flavonoids
in Biology and Medicine”,
Alan Liss, New York. |
(6) |
Sonnenblicher
& Zetl, 1986, Prog.
Clin Biol. Res. 213,
319 |
(7) |
Sonnenblicher
& Zetl, 1987, in
“Assessment &
Management of Hepatobiliary
Disease”, Springer,,,
New York. |
(8) |
Fintelmann
& Albert, 1980;
Therapy week 30, 5589. |
(9) |
Dehmlow
et al, 1996; Life Science
58, 1591. |
(10) |
Dehmlow
et al, 1996; Hepatology,
23, 749. |
(11) |
Zhao
& Agrawal, 1999;
carcinogenesis, 20,
2101. |
(12) |
Valenzuela
et al, 1989; Planta
Medica, 55, 420 |
(13) |
Ference
et al, 1989; J. Hepatol,
9, 105 |
(14) |
Salmi
& Sarna, 1982; Scand.
J. Gastroenterol. 17,
517 |
(15) |
Monograph
of commission E of the
federal German Health
Authority, March 1986 |
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