Patent GB-783486-A (GB)
Title: A new antibiotic filipin
Filed: 1955-11-22
Abstract: <PICT:0783486/IV (a)/1> <PICT:0783486/IV (a)/2> A new antibiotic, filipin, is produced by cultivating a filipin-producing-strain of Streptomyces filipinensis, especially S. filipinesis NRRL-2437 under aerobic conditions in a nutrient medium containing a source of (a) carbon, (b) nitrogen, (c) nutrient inorganic salts, and (d) trace elements.  Specified carbon sources are sucrose, lactose, glucose, starch, molasses, glycerol and dextrin (all preferred), xylose, arabinose, fructose, galactose, maltose, rappinose, inulin, mannitol, inositol, sodium acetate, sodium citrate, sodium succinate, dextrose and mannose. Nitrogen sources are distillers solubles, cottonseed meal and flour, yeast, peptone, soybean meal, ammonium salts and nitrates. Inorganic salts are such as produce ions of sodium, potassium, calcium, phosphate, chloride and sulphate.  Calcium carbonate may also be present.  Temperature of cultivation is 23 DEG to 32 DEG  C. and especially 24 DEG  to 28 DEG  C., duration is 2 to 5 days for submerged culture (preferred) and 4 to 12 days for surface culture.  Filipin is recovered from the fermentation broth by (A) solvent extraction with a polar organic solvent at pH 2.3 to 10.4 or (B) adsorption and elution with a polar organic solvent in which filipin is soluble.  It is preferred to extract the filtered broth, but the whole broth and the mycelium per se may also be extracted. Specified solvents are n-butanol and ethyl acetate (both preferred), dimethylformamide, pyridine, methanol, isopropanol, tert.-butanol, ether and amyl acetate.  Filipin is recovered from the extract by (a) removal of the solvent or (b) addition of a non-solvent especially a petroleum hydrocarbon such as hexane and heptane.  Further purification is obtained by treatment with chloroform and Skellysolve B to remove impurities.  Specified adsorbents are activated alumina, silica gel, magnesium aluminium silicate and acetic acid activated carbon.  Filipin crystals melt at 195 DEG  to 205 DEG  C. with decomposition; specific rotation [a ]22D=minus 148.3 (c, 0.89 methanol); contains only carbon, hydrogen and oxygen in proportions of C= 60.95 per cent, H = 8.90 per cent and O (by dif.) 30.15 per cent; it is soluble in dimethylformamide, pyridine, 95 per cent ethanol, methanol, n-butanol, isopropanol, tert.-butanol, glacial acetic acid, ether, ethyl acetate and amyl acetate, insoluble in water, chloroform, 50 per cent aqueous ethanol, methylene chloride, hexane and heptane. Ultraviolet absorption spectrum maxima (95 per cent ethanol) at 355 mm , 338 mm  and 322 mm ; exhibiting a characteristic absorption in the infra-red when suspended in petroleum oil at the following frequencies expressed in reciprocal centimetres 3580, 3360, 1715, 1177, 1137, 1085, 1040, 1005 and 840. Filipin has antifungal properties and is used in medicinal veterinary and agricultural preparations (see Group VI).ALSO:A new antibiotic filipin (see Group IV (b)) is used in pharmaceutical, veterinary and agricultural preparations for the treatment of fungal diseases. Medicinally it is used for internal or external administration. Filipin may be compounded with the following medicines (a) antibiotics such as erythromycin, streptomycin, dihydrostreptomycin, chloramphenicol, oxytetracycline, chlortetracycline, tetracycline, polymixin B, bacitracin, alkali metal salts of penicillin, procaine penicillin, N,N1-dibenzylethylenediamine penicillin and neomycin sulphate and with sulphonamides; (b) antifungal agents such as alkyl p-hydroxybenzoates, sodium caprylate, calcium propionate, zinc caprylate, propionic acid, salicylanilide and undecylenic acid; (c) steroids such as cortisone, hydrocortisone esters and water-soluble derivatives, halo steroids such as 9a -chlorocortisone, 9a -fluorocortisone, 9a -chlorohydrocortisone, 9a -fluorohydrocortisone esters and water-soluble derivatives thereof; and (d) antibacterial agents such as cresols, phenol, resorcinol, diphenols, dyes such as gentian violet, fuchsia and methyl violet and nitrofurazone.