Patent GB-791774-A (GB)
Title: Purification of basic antibiotics using ion exchange resins
IPC: A61K47/48
Filed: 1955-08-24
Abstract: Basic antibiotics are purified by contacting an impure aqueous solution of the antibiotic with an at least partially neutralized carboxylic acid ion-exchange resin of limited porosity (A), eluting the antibiotic from the resin with a dilute acid and then contacting the eluate from said resin with either an at least partially neutralized carboxylic acid ion exchange resin of high porosity (B) or with a sulphonic acid ion exchange resin in the acid form (C).  By limited porosity is meant a resin showing little change in volume when contacted with water, e.g. a copolymer of methacrylic acid, or an ester thereof, with 6 to 12 per cent by weight of a divinyl aromatic compound such as divinyl benzene, divinyltoluene and divinylnaphthalene.  By high porosity is meant a resin capable of adsorbing a high proportion of organic bases of molecular weight above 150.  The resins show a large increase in volume when contacted with water, e.g. a copolymer of acrylic acid with 1 to 15 per cent of a divinyl aromatic compound, e.g. divinyl benzene or a copolymer of methacrylic acid with 1 to 4 per cent of a divinyl aromatic compound which is at least partially neutralized, e.g. Amberlite XE 89.  The sulphonic acid ion exchange resin is a sulphonated polystyrene copolymerized with 10 to 25 per cent of a divinyl aromatic compound, e.g. Dowex 50. The carboxylic acid resins are equilibrated at pH 6 to 9 with alkali e.g. aqueous sodium hydroxide and are preferably in beadlet form.  The sulphonic acid ion exchange resin is in the acid form and is used at pH of 1.0 to 2.5.  The antibiotic is eluted from the carboxylic acid ion exchange resin by a dilute acid, e.g. sulphuric, hydrochloride or hydrobromic.  Excess acid may be removed from an eluate by (a) an anion exchange resin or (b) addition of a substance which forms a precipitate with the acid, e.g. barium hydroxide or barium carbonate for sulphuric acid and silver carbonate for hydrochloric acid.  The final eluate or effluent may be treated with carbon and the antibiotic precipitated by the addition of a water-miscible organic solvent, e.g. methanol or ethanol.  A filtered fermentation broth is the preferred source of the antibiotics.  A three-stage process in which resins (A), (B) and (C) are used in that order is preferred. Examples illustrate the purification of (a) streptomycin from a fermentation broth using the three-stage process, the final product being 95 per cent pure and free from streptidine, (b) riomycin using both a two-stage and a threestage process, and (c) neomycin using both the two- and the three-stage process.  Other basic antibiotics which may be purified by the processes of the invention are dihydrostreptomycin, hydroxystreptomycin, streptothricin and mannosidostreptomycin.  The antibiotics are produced substantially free of pyrogens and histamine-like materials. Salts of the carboxylic acid ion exchange resins with the basic antibiotics may be used for feed enrichment.ALSO:For feed enrichment may be used salts of basic antibiotics such as streptomycin, neomycin, viomycin, streptothricin, marrosidostreptomycin, hydroxystreptomycin and dihydrostreptomycin with carboxylic acid ion exchange resins. (See Group IV(b)).