Patent GB-935075-A (GB)
Title: The antibiotic decoyinine and the manufacture thereof
IPC: C12P19/40
Filed: 1959-12-03
Abstract: The new antibiotic designated Decoyinine (or antibiotic a14) is produced by cultivating Streptomyces hygroscopius var. decoyinine in an aqueous nutrient medium under aerobic conditions, preferably submerged, said nutrient medium containing assimilable sources of carbon and nitrogen compounds or proteinaceous material and inorganic salts.  Specified sources of carbon are carbohydrates, e.g. glucose, galactose, maltose, dextrin, molasses; corn meal, starch or mixtures thereof, mannitol, soyabean oil or animal or vegetable oils. Specified sources of nitrogen are protein sources, e.g. cottonseed meal, soyabean meal, fish meal, defatted soyabean meal or peptone and other sources, e.g. peanut meal, Brewer's yeast, yeast extract, corn gluten meal, corn steep liquor, fish stick liquor, animal stick liquor, distillers solubles, tripticase, tryptone, beef extract, N-Z amine A, N-Z amine B, proteolized milk or egg products.  Specified inorganic salts are those providing potassium, sodium, calcium; phosphate or sulphate ions.  Trace elements, e.g. zinc, magnesium, manganese, cobalt or iron may also be present.  Cultivation at a temperature from 24 DEG  to 37 DEG C. for two to seven days at an initial pH of 6,5 to 7,6 is preferred.  An antibiotic psicofuranine and the known compound adenine are also produced by this method of cultivation.  The antibiotic decoyinine is isolated from the fermented broth by extraction or absorption on carbon or a capillary absor <PICT:0935075/IV(a)/1> <PICT:0935075/IV(a)/2> bent.  Solvent extraction is preferred.  In the adsorption technique the fermented broth is filtered at an acid pH, the filtrate is made alkaline and absorbed on an adsorbent.  The absorbent cake is slurried with an organic solvent, e.g. acetone, filtered and the filtrate distilled, filtered, neutralised and freeze dried to give impure decoyinine. The decoyinine is purified by counter current distribution or counter current liquid-liquid extraction, and may be separated from psicofuranine by the Craig counter current distribution with a solvent system of equal parts of n-butanol and water.  Decoyinine and psicofuranine may be acylated with pyridine/acetic anhydride, e.g. decoyinine forms a tetra-acetate m.p. 65 DEG C. and a penta-acetate m.p. 152-153 DEG C., psicfuranine forms pento- and hexa-acylates.  On acid hydrolysis decoyine forms adenine and a sugar moiety of empirical formula C6H12O5.  Sodium borohydride does not reduce decoyinine.  Psicofuranine has the following formula:- <FORM:0935075/IV(a)/1> The two antibiotics have the following properties:-  <TABS:0935075/IV(a)/1> The I.R. spectrum of decoyinine is shown in Fig. 1 and its U.V spectrum in Fig. 2.  Decoyinine and its acylates are active against bacteria and fungi and in the treatment of hemolytic streptoccal infections in animals and persistant urinary tract infections in humans.  It is used in animal and poultry feedstuffs and in human and veterinary medicines (see Group VI). Specification 815,518 is referred to.ALSO:A pharmaceutical composition for oral, parenteral and topical administration to humans and animals comprises the antibiotic decoyinine or its acylates (see Group IV (b)) and a pharmaceutically acceptable carrier, which is a solid, a powder or a liquid.  The antibiotic, either alone or in admixture with other antibiotics, is used as a feed supplement for promoting the growth of animals or poultry.  Specified oral forms are tablets, effervescent tablets, capsules, suspensions in edible oils, or aqueous suspensions.  Solid diluents are corn starch, lactose, talc, stearic acid, dicalcium phosphate, magnesium stearate or gums. Suspensions in a fixed oil containing 2% aluminium stearate can be administered alone or in capsule form. For parenteral use sterile aqueous or oil suspensions with or without hydrophilic colloids such as sodium carboxymethyl cellulose, polyvinyl pyrrolidone, gelatin, alginates or tragacanth are used.  Typical forms specified are petrolatum type grease base and polyethylene glycol water-soluble base ointments, creams, water-in-oil emulsions, lotions, ear drops, eye drops, aerosols, nasal sprays, troches and suppositories. Veterinary forms specified are bougies and mastitis ointments.  The compositions may also contain other medicaments.  (a) Sulphur drugs, e.g. sulphadiazine, sulphamerazine, sulphanilamide, sulphamethazine, sulphacetamide or sulphamethylthiadiazole; (b) antibiotics, e.g. tetracycline, oxytetracycline, chlortetracyline, penicillins, novobiocin, neomycin, psicofuranine, erythromycin, streptomycin, bacitracin, polymixin chloramphenicol, kanamycin, nyastatin or streptozotocin; (c) vitamins, e.g. thiamine, riboflavin, ascorbic acid, macinamide, pyridoxine, pantothenic acid or pantothenate salts, Vitamin B12, or folic acid; or (d) corticoids, e.g. cortisone, hydrocortisone, prednisone and prednisolone, their esters such as the acetate or cyclopentylpropionate or succinate and sodium salts, also their fluoro, methyl and hydroxy analogues, e.g. 6a  fluorohydro cortisone, 16 hydroxy-9a  fluorohydrocortisone and 16 methyl-9a -fluoro prednisolone and esters thereof.  A specified composition comprises adenine, psicofuranine (see Group IV (b)) and decoyinine. Specification 815,518 is referred to.