Patent GB-874028-A (GB)
Title: Derivatives of antibiotics having a basic reaction, and a process for their preparation
IPC: C07G11/00
Filed: 1959-07-14
Abstract: Aminoalkane sulphinates and/or aminoalkane sulphonates of antibiotics which have reduced toxicity while retaining their antibiotic activity are produced by reacting a basic antibiotic having at least one free basic group with a salt of a hydroxyalkane sulphinic acid or of a hydroxyalkane sulphonic acid in a liquid medium, the said basic antibiotic being one which will react with the said salt to form the said condensation product. The hydroxyalkane sulphinic or sulphonic acid preferably has 1 to 4 C atoms in the alkyl group and the preferred salt is the sodium salt.  The salt can be replaced by a reactive mixture capable of forming them in situ, e.g. a mixture of an aldehyde and sodium bisulphite.  The antibiotic may be used in the form of a salt with a weak acid, e.g. carbonate, the antibiotic base being formed in situ.  The condensation products produced are of the general formula R-3NH-R1-SO2-M1)p R-(NH-R1-SO3-M1)p where R represents a basic antibiotic deprived of p free amine functions, R1 is an alkyl radical and M1 is an alkali metal, ammonium or amine radical.  The basic antibiotic may be such as has at least one free amine function and at least one neutralised amine function and the resulting condensation product after separation from the reaction medium is so treated as to eliminate the metal atom or atoms and the group neutralising at the said neutralised amine function.  The amine function is neutralised by acids and the metal atoms and acids are removed from the condensation products by (a) mixed anion and cation exchange resins or (b) salts the cation of which gives insoluble compounds with the groups (i.e. acids) blocking the amine function and the anion of which combines with the metallic ion to form a soluble salt which remains in solution when the condensation product is precipitated by the addition of a non-solvent, e.g. barium acetate.  Such compounds have the general formula <FORM:0874028/IV (b)/1> and <FORM:0874028/IV (b)/2> wherein R1-(NH2)a represents a basic anti biotic deprived of p out of a total of p + q amine functions. Typical compounds are sodium neomycin hexamethane sulphinate, sodium kanamycin tetramethane sulphinate, sodium dihydrostreptomycin trimethane sulphinate, sodium neomycin hexamethane sulphonate, sodium dihydrostreptomycin tri-methane sulphonate, sodium kanamycin tetramethane sulphonate, monosulphate of sodium kanamycin dimethane sulphinate and kanamycin dimethane sulphonic acid.  The condensation products may be used in pharmaceutical compositions (see Group VI).ALSO:Pharmaceutical preparations comprise a carrier and an aminoalkane sulphinate or an aminoalkane sulphonate of a basis antibiotic having at least one free basic group, said antibiotic derivative having the general formula R-(NH-R1-SO2-M1)p R-(NH-R1-SO3-M1)p where R represents a basic antibiotic deprived of p free amino functions, R1 is an alkyl radical and M1 is an alkali metal, ammonium or amine radical.  Typical antibiotics are sodium neomycin hexamethane sulphinate, sodium kanamycia tetramethane sulphinate, sodium dihydrostreptomycin trimethane sulphinate, sodium neomycin hexamethane sulphonate, sodium dihydrostreptomycin trimethane sulphonate, sodium kanamycin tetramethane sulphonate, monosulphate of sodium kanamycin dimethane sulphinate and kanamycin dimethane sulphonic acid.