GB793491A - Process of recovering basic antibiotics - Google Patents

Abstract

Nitrogen basic antibiotics such as neomycin, streptomycin and streptothricin are recovered from a fermentation broth, or an acid filtrate thereof, by adsorption on a particulate cation exchanger in its amine salt form, and elution therefrom with a dilute mineral acid such as hydrochloric, nitric or sulphuric at pH 1.5 to 4.5. It is preferred however to elute with mineral acid of pH 4.5 to 6 to remove any alkali or alkaline earth metals before removing the antibiotic by elution at pH 1.5 to 4. Ion exchange resins deriving their exchange capacity essentially from carboxylic groups, e.g. Alkalex, "Amberlite" IRC-50 (Registered Trade Mark), "Duolite" CS 100 (Registered Trade Mark), "Permutit" H-70 (Registered Trade Mark), and "Wolfatit" C may be used. The cation exchanger is treated with the organic amine as such, if liquid, or in solution in water or aqueous organic solvent, e.g. aqueous ethanol, in order to be converted to the salt form. Specified amines are primary, secondary and tertiary aliphatic amines such as methylamine, diethylamine and triethylamine, the primary, secondary and tertiary cycloaliphatic amines, e.g. cyclobutylamine; the primary, secondary and tertiary araliphatic amines, e.g. benzylamine; and heterocyclic amines, e.g. piperidine, pyrrolidine morpholine and their alkyl substituted derivatives. Preferably the amine is such that its salt with the eluting acid has a different solubility from the salt of the antibiotic with the eluting acid. The process may be batch or continuous. It is preferred to use the acid filtrate obtained by acidifying the broth to a pH of 1.5 to 3 with mineral acid and filtering with a filter aid. The pH is then adjusted to pH 5 to 9.5, and preferably 7 to 8.5 with an amine. If desired, a sequestering agent for alkaline earth cations, ethylenediamine tetraacetic acid may be added to the acid or neutralized filtrate before the adsorption step. After elution, the eluate is adjusted to pH 5 to 7 by means of an anion exchange resin, e.g. "Amberlite" IR-4B, concentrated if desired, and the antibiotic precipitated by means of a non-solvent in which the salt of the amine with the eluting acid is soluble. Such solvents are the water-miscible alcohols, e.g. methanol and ethanol; the watermiscible ketones, e.g. acetone; the watermiscible ethers, e.g. dioxane; water-miscible nitriles, e.g. acetonitrile and the water-miscible amides, e.g. dimethyl formamide. The antibiotic salt may be vacuum or freeze dried or converted to the free base.