Description
Enviomycin was found in the culture broth of Streptomyces griseoverticillatus var. tuberacticus by Toyo Jozo Co. in 1966 as a mixture of tuberactinomycins N and O. It is a water-soluble, basic peptide closely related to viomycin and showing selective activity against Mycobacterium species about twice as strong as that of viomycin. Enviomycin, in combination with other antituberculotic drugs, is used to treat tuberculosis caused by streptomycinresistant Mycobacterium.
Originator
Tuberactin,Toyo Jozo,Japan,1975
Manufacturing Process
Two liters of an aqueous medium consisting of glucose 3%, starch 2%,
soybean meal 3% and sodium chloride 1.5% were equally divided and
introduced into twenty 500-ml Erlenmeyer flasks, adjusted to pH 6, sterilized
at 120°C for 30 minutes, inoculated with Streptomyces griseoverticillatus var.
tuberacticus N6-130 and then rotatively shake-cultured (radius 2.5 cm, 330
rpm) at 30°C for 7 days, obtaining 1.5 liter of cultured broth containing 2,360
mcg/ml of tuberactinomycin-N.
Filtered broth was passed at 2.5 ml/min through a resin column (2.5 cm
diameter, 28 cm length) packed with 150 ml of ion exchange resin Amberlite
IRC-50 sodium type (Rohm and Haas Co., USA.). The column was washed
with water, eluted with 0.5N HCl at a flow rate 1.3 ml/min. The eluates were
fractionated each 10 ml and tuberactinomycin-N activity was found at
fractions No. 45-63 observed by ultraviolet absorption method and bioassay.
The thus yielded active fraction, about 200 ml, was neutralized with sodium
hydroxide, concentrated to about 15 ml in vacuo, separating the precipitated
inorganic salts therefrom. After decolorization with active carbon, 150 ml of
methanol was added, the mixture was allowed to stand overnight at 5°C and
the precipitate was collected by filtration. The precipitate was washed withmethanol and dried in vacuo to yield crude tuberactinomycin-N hydrochloride
(yield, 3.07 g; purity, 7 1.5%; recovery, 62%).
