Medicinal
Technologies -
Compactin Production Technology
Introduction
Romanian company, through its Germany
and Italy based associates, offers the technology for
production of Compactin, ML-236B - Generic name (USAN)
Mevastatin.
The technology offered does not conflict with any existing
patent. The technical details are: Name: 2-Methyl-butanoic
acid-1,2,3,7,8,8a-hexahydro-7-methyl-8[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-
naphthalenyl ester Empirical formula: C23 H34 O5+ Molecular
weight: 390.52 Strain classification: Compactin is produced
by Pencillium citrinum, in this case a mutant is selected
for high productivity. Pharmaceutical use: Coronary
artery disease is an exceptionally important problem
in industrial society and is often associated with arteriosclerosis,
a condition in which esterified and free cholesterol
is deposited in thinner walls of coronary arteries.
Extensive epidemiological studies have established a
link between abnormally high level of low density lipoprotein
cholesterol and the incidence of coronary arteriosclerosis.
Compactin is a precursor drug which could be transformed
to pravastatin that treats hypercholesterolemia. Pravastatin
is the principle metabolite and a potent inhibitor of
3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase.
This enzyme catalyzes the conversion of hydroxymethylglutarate
to mevanolate, which is an early and rate limiting step
in biosynthesis of cholesterol. The effectiveness of
Pravastatin in lowering cholesterol has been confirmed
clinically and it is approved for the treatment of primary
hypercholesterolemia. Process description: Pencillium
citricum is grown on agar medium for 10-14 days. Flasks
are inoculated with a piece of well grown agar culture
and cultivated on a shaker. After 48 hours cultivation
time the culture is completely transferred to the production
fermenter. The productive fermenter is fed with sterile
solution of Glucose to maintain the optimal concentration
of Carbon source. The fermentation broth is transferred
to the recovery section where the product is extracted
by solvents, hydrolysed under agitation and purified
by chromatography. During these operations, pH and temperature
are automatically controlled.
Area of Application:
Pharmaceutical industry, medicine, biotechnology: Compactin
is a precursor drug which could be transformed to pravastatin
that treats hypercholesterolemia.
Contact:
Asian and Pacific Centre for Transfer
of Technology
APCTT Building
C-2 Qutab Institutional Area
P.O.Box - 4575
New Delhi - 110 016
Tel : 91-11-26966509
Fax : 91-11-26856274
