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.

For further information please contact

Asian and Pacific Centre for Transfer of Technology
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