http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-787895-A

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classificationCPCInventive http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07C233-00
http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C12P29-00
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http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C12P29-00
filingDate 1954-11-02-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 1957-12-18-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber GB-787895-A
titleOfInvention Production of the antibiotic tetracycline by fermentation
abstract Tetracycline is produced by cultivating Streptomyces species ATCC 11652, 11653 and 11654, or a mutant thereof, in an aqueous nutrient medium under submerged aerobic conditions. The medium contains a source of (a) carbohydrate, e.g. molasses, glucose, starch or glycerol, (b) nitrogen, e.g. soyabean meal, wheat gluten, peanut meal, hydrolysate of casein and proteins, (c) growth stimulants, e.g. corn steep liquor, distillers solubles and yeast extract, (d) mineral salts, e.g. sodium chloride, sodium nitrate, potassium phosphate and magnesium sulphate, (e) buffer, e.g. calcium carbonate and antifoaming agent. Cultivation is at 25-30 DEG C. and preferably 28 DEG C. for 2 to 6 days. The crude broth may be freeze dried before or after filtration of the mycelium to produce a product used as an animal feed supplement or plant growth stimulant. Tetracycline is recovered by (a) adsorption, (b) precipitation by means of an organic base, an aryl azo sulphonic acid dye or a complex with a polyvalent metal of Group II, (c) solvent extraction. Adsorption is by means of activated carbon, active earths or ion exchange resins especially sulphonic acid resins at pH 3 to 8. Solvent extraction is at pH 1 to 2.5 or 7.5 to 10 using a water-immiscible organic solvent such as butanols, pentanols, benzyl alcohol, phenylethylalcohol, glycol ethers, e.g. 2-phenoxyethanol, ketones, e.g. methyl isobutyl ketone, esters such as amyl acetate, propyl acetate and ethyl propionate. The extraction is preferably carried out in the presence of a sequestering agent for polyvalent ions, e.g. polyphosphates, various hydroxy acids such as gluconic acid, citric acid and tartaric acid and amino acids such as ethylene diamine tetraacetic acid. For precipitation as a metal ion complex, one or more of the metal ions in the form of a watersoluble salt is added to the clarified broth and the pH is adjusted to 7.5 to 9 to precipitate the complex. Metals specified are barium, calcium, magnesium, strontium, beryllium, mercury and cadmium. A non-toxic complex, e.g. calcium and magnesium can be used per se. Generally, the metals are precipitated from a solution of the complex and the antibiotic recovered from the residual solution. For precipitation with an organic base, the base is added to the clarified broth and the pH adjusted to 8-9.5. Preferably a sequestering agent is present. Specified bases are C8 to C18 alkyl trimethyl ammonium halides, C8 to C18 alkyl dimethyl benzyl ammonium halides, alkyl substituted imidazolines and alkyl amines. The precipitate is dissolved in a solvent, e.g. methanol and the antibiotic recovered by addition of a mineral acid. In the case of the dye complex, the dye is added to the acidified clarified broth. Further purification of the antibiotic obtained by any of the above recovery processes is by dissolving the antibiotic in acidified water and extracting with a water immiscible solvent, e.g. butanol. Specification 749,779, [Group V], is referred to.
priorityDate 1953-11-12-04:00^^<http://www.w3.org/2001/XMLSchema#date>
type http://data.epo.org/linked-data/def/patent/Publication

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