Patent GB-976765-A (GB)
Title: Improvements in or relating to antibiotics and the manufacture thereof
IPC: A23K20/195
Filed: 1962-05-11
Abstract: <PICT:0976765/C1/1> The antibiotic lincomycin, sometimes known as lincolnensin, is produced by cultivating Streptomyces lincolnensis var. lincolnensis in an aqueous nutrient medium containing sources of carbon and nitrogen under aerobic conditions, preferably at 18-40 DEG C. for a period of 2-5 days. The antibiotic is isolated by adjusting the culture filtrate to a pH of 7.5 or more and extraction of said filtrate with a water-immiscible solvent. The antibiotic is recovered from the solvent extract by precipitation as an insoluble acid addition salt or by extracting with an aqueous solution of an acid which forms a water soluble salt e.g. HCl, H2SO4, H3PO4 or CH3.COOH. <PICT:0976765/C1/2> The antibiotic can also be recovered from the culture filtrate by adsorption on a cation exchange resin of both the carboxylic and sulphonic type and elution with water at an acid pH or from the culture filtrate and other aqueous solutions by adsorption on a surface-active adsorbent, e.g. carbon resins, and elution with a solvent for the antibiotic.  The antibiotic is purified by transfers from protonated to non-protonated form, solvent extraction, fractional liquid/liquid extractions and recrystallization.  Other salts mentioned are those formed with helianthic, Reinecke's, azobenzene sulphonic, picric, succinic, lactic, maleic, fumaric, methane sulphonic and benzene sulphonic acids. The free base is formed by treatment of the salt with an alkali or an anion exchange resin. The antibiotic Lincomycin is monobasic having a Pka1 of 7.6; no U.V. maxima from 220-400 mm ; an empirical formula C18H34N2O6S; soluble in lower alkanols, alkyl esters, alkanoic acids, alkanones and chlorinated alkanes of 1-8 carbon atoms, and having in the form of its hydrochloride an I.R. spectrum as shown in Fig. 3, a melting point of 135-140 DEG C., an optical rotation <FORM:0976765/C1/1> (c=1% in water) and an equivalent weight of 454.7 and a papergram pattern as shown in Fig. 2.ALSO:The antibiotic lincomycin (see Division C2) or its pharmacoligically-acceptable acid addition salts are (a) fed to animals and birds in order to promote growth or are (b) added to cheese or milk to prevent attack by micro-organisms. The antibiotic may be mixed with other antibacterial agents.  A specified feed containing the antibiotic comprises soybean meal, fish meal, wheat germ oil and sorghum molasses.ALSO:A therapeutic and antibacterial composition comprises the antibiotic lincomycin or a pharmacologically acceptable acid addition salt thereof (see Division C2), many are specified, and a carrier, e.g. for use in the treatment of tonsillitis, pneumonia, otitis, conjunctivitis, boils and carbuncles, by oral, parenteral or topical administration.  Specified forms are tablets e.g. laminated tablets capsules pills, powders granules, ampoules, troches, suppositories, cachets, vials, syrups, chewing gum, sterile solutions or suspensions for parenteral use, elixirs, emulsions, ointments, creams, lotions, tablets having an inner layer which is enteric coated e.g. with shellac, cetyl alcohol, cellulose acetate phthalate or styrene maleic acid copolymer and wafers.  Capsules may be filled with polymeric acid coated beads containing the antibiotic.  The compositions may contain other antibiotics e.g. actinospectacin, chloramphenicol, tetracycline, oxytetracycline, chlortetracycline, penicillin, erythromycin, novobiocin, kanamycin, sodium novobiocin, calcium novobiocin, hydrochlorides of the tetracyclines, tetracycline phosphate complex, streptomycin, dihydrostreptomycin neomycin, polymixin and its sulphate, bacitracin, nystatin, filipin, fumagillin and endomycin; steroids e.g. hydrocortisone, prednisolone and its succinate and acetate, 6a -methyl prednisolone and 6a -fluoroprednisolone; analgesics e.g. aspirin, sodium salicylate, (acetyl-salicylic acid)-anhydride, N-acetyl - p - amino phenol and salicylamide; antihistamines e.g. chlorpheneramine maleate, diphenhydramine, promethazine and pyrathiazine; sulpha drugs e.g. sulphadiazine, sulphamethazine, sulphamerazine, sulphacetamide, sulphadimethyl oxazole and sulphamethazole; antifungal agents e.g. undecyclenic acid, sodium propionate, salicylanilide, sodium caprylate and hexetidine and vitamins and local anaesthetics e.g. lidocaine hydrochloride and benzocaine.  Wash solutions and rinses are used for treating equipment, paper and fabrics to destroy or inhibit the growth of bacteria.