Process for producing L-leupeptins

Abstract

DL-leupeptins have been known to be produced by leupeptins-producing organisms and only L-leupeptins have bioactivity. This invention provides the processes for production of L-leupeptins in high yield and for its extraction without racemization. L-leupeptins may be efficiently produced by inoculating a leupeptins-producing strain of Streptomyces into a medium containing nutrient sources and aerobically cultivating under the condition of pH 5.0 to 7.0. Production of L-leupeptins is markedly increased by adding to the medium each 0.5 to 1.25% (wt/vol) of L-leucine, L-arginine (as hydrochloride), and glycine, and is further increased by adding to the medium 0.05 to 0.3% (wt/vol) of at least one of the yeast extract, casein hydrolyzate, and ribonucleic acids, in addition to the above amino acids. Efficient separation of L-leupeptins of acceptable purity from the cultured broth can be effected by use of a nonionic adsorbent resin, wherein the pH is controlled always to be 7.0 or lower. L-leupeptins thus obtained inhibit plasmin, tripsin, cathepsin B and papain, and the ointment containing L-leupeptins have been confirmed to be effective in treatment of inflammation, ulceration and burn of skin surface, erythematosis, skin transplantation, etc.

Dependencies are inferred from the claim text.