Patent GB-808362-A (GB)
Title: Improvements relating to the recovery of tetracycline antibiotics from crude fermentation liquors and purified antibiotics resulting therefrom
Filed: 1955-08-16
Abstract: Tetracycline, oxytetracycline, chlortetracycline and bromotetracycline are separated from fermentation mash impurities by precipitating an insoluble form of the antibiotic from an aqueous solution thereof in the presence of a water-soluble synthetic polymeric polyelectrolyte flocculating agent having an average molecular weight of at least 10,000 and a structure derived by the substantially linear polymerization of at least one mono-olefinic compound through the aliphatic unsaturated group, and separating the so formed solid from the aqueous phase. The antibiotic is precipitated as a compound with a surface active sulphate or sulphonate particularly one of general formula R-On-SO3H in which R represents a hydrophobic group and n is zero or 1.  Preferably there is also present a heavy metal chelating agent where pK for calcium is at least 7.  The pH is 2 to 10 and preferably 5 to 8.  It is preferred to add the flocculating agent in aqueous solution.  The suspension may be heated.  The surface-active sulphates or sulphonates are those of Specification 717,281, e.g. sodium heptadecyl sulphate and the sodium salt of di-2-ethylhexylsulphosuccinate.  Specified chelating agents are: ethylene diamine tetraacetic acid; trimethylenediamine tetraacetic acid; trinitrilo triacetic acid; N1-(2-hydroxy ethyl) ethylenediamine - N,N,N1-triacetic acid; 1,2 - diaminocyclohexane - N,N,N1,N1-tetraacetic acid; dipropylene - 1,2 - triamine pentaacetic acid; 1,3-diamino 2-propanol tetraacetic acid; 2-[bis (carboxymethyl) amino] ethyl ether; bis-[2-(N,N - carboxymethyl) - aminoethoxyl ethane; 2 - aminoethyl phosphonic acid - N,N - diacetic acid; aminobarbituric acid-N,N-diacetic acid; 1,2-propylene diamine tetraacetic acid; diethylene triamine pentaacetic acid; and the alkali metal, amine and ammonium salts of said acids.  Specified flocculating agents are polymers of acrylic acid, salts of polymers of acrylic acid, salts of hydrolysed polymers of acrylonitrile, hydrolysed polymers of acrylonitrile, polymers of methacrylic acid, salts of polymers of methacrylic acid, salts of hydrolysed polymers of methacrylonitrile, hydrolysed polymers of methacrylonitrile, salts of copolymers of unsaturated polycarboxylic acids and at least one other mono-olefinic monomer, copolymers of unsaturated polycarboxylic acids and at least one mono-olefinic monomer, hydrolysed copolymers of unsaturated polycarboxylic acid anhydrides and at least one other mono-olefinic monomer and salts thereof, copolymers of unsaturated dicarboxylic acid anhydrides and at least one other mono-olefinic monomer, copolymers of the partial alkyl esters of unsaturated polycarboxylic acids and at least one other olefinic monomer and salts thereof, salts of sulphonated polymers of hydrocarbons containing aliphatic unsaturation, sulphonated polymers of hydrocarbons containing aliphatic unsaturation, polymers of amines or amides containing aliphatic unsaturation, said polymeric compound being derived substantially entirely by olefinic polymerization and preferably having an average molecular weight of between 10,000 and 250,000. Examples are "Vama" "Krilium" and "Aerotil."  Reference has been directed by the Comptroller to Specification 781,811.