ASTROMICIN SULFATE

ASTROMICIN SULFATE Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Astromicin sulfate is a pseudodisaccharide aminoglycoside antibiotic with a spectrum comparable to amikacin. It is active against many gentamicin and amikacin resistant bacteria expressing aminoglycoside-modifying enzymes, with the exception of aminoglycoside 3-acetyltransferase.

• Originator

  Kyowa Hakko (Japan)

• Definition

  ChEBI: Astromycin sulfate is an aminoglycoside sulfate salt. It is functionally related to an astromicin.

• Manufacturing Process

  Aminoglycoside antibiotic complex produced by Micromonospora used as a seed strain. One loopful of the seed strain is inoculated into 10 ml of a seed medium containing 2% glucose, 0.5% peptone, 0.5% yeast extract and 0.1% calcium carbonate (pH 7.5 before sterilization) in a 50 ml large test tube. Culturing is carried out at 30°C for 5 days. 10 ml of the seed culture broth is then inoculated into 30 ml of a second seed medium in a 250 ml Erlenmeyer flask. The composition of the second seed medium is the same as that of the first seed medium. The second seed culturing is carried out at 30°C for 2 days with shaking. Then 30 ml of the second seed culture broth is inoculated into 300 ml of a third seed medium in a 2 L Erlenmeyer flask provided with baffles. The composition of the third seed medium is the same as that of the first seed medium. The third seed culturing is carried out at 30°C for 2 days with shaking and 1.5 L of the third seed culture broth (corresponding to the content of five flasks) is inoculated into 15 L of a fourth seed medium in a 30 L glass jar fermenter. The composition of the fourth seed medium is the same as that of the first seed medium. Culturing in the jar fermenter is carried out at 37°C for 2 days with aeration and stirring (revolution: 350 r.p.m., aeration: 15 L/min). Thereafter, 15 L of the fourth seed culture broth is inoculated into 150 L of a main fermentation medium in a 300 L fermenter. The main fermentation medium comprises 4% soluble starch, 2% soybean meal, 1% corn steep liquor, 0.05% K2HPO4, 0.05% MgSO4·7H2O, 0.03% KCl and 0.1% CaCO3 (pH 7.5 before sterilization). Culturing in the fermenter is carried out at 37°C for 4 days with aeration and stirring (revolution: 150 r.p.m., aeration: 80 L/min).
  After the completion of culturing, the resulting fermentation broth is adjusted to a pH of 2.5 with concentrated sulfuric acid, and stirred for 30 minutes. Then, about 7 kg of a filter aid, Radiolite No. 600 (product of Showa Kagaku Kogyo Co., Ltd., Japan) is added thereto and the microbial cells are removed by filtration. The filtrate is adjusted to a pH of 7.5 with 6 N sodium hydroxide and passed through a column packed with about 20 L of a cation exchange resin, Amberlite IRC-50 (ammonium form), and the effluent is discarded. Active substances are adsorbed on the resin. After washing the resin with water, the adsorbed active substances are eluted out with 1 N aqueous ammonia. Activity of the eluate is determined by a paper disc method, using an agar plate of Bacillus subtilis No. 10707. The active fractions are collected and the mixture is concentrated to about 1 L under reduced pressure. The concentrate is passed through a column packed with 500 ml of an anion exchange resin, Dowex 1x2 (OH- form). Then, about 2 L of water is passed through the column, whereby impurities are removed and active substances are eluted out. The thus obtained active fractions are collected, and concentrated to about 100 ml under reduced pressure, and the resulting concentrate is passed through a column packed with about 50 ml of active carbon powder. The active substances are adsorbed onto the carbon powders. Then, the column is washed with water and the effluent and the washing water are discarded. Then, the adsorbed active substances are eluted out with 0.2 N sulfuric acid. Activity of the eluate is determined by the paper disc method using Bacillus subtilis, and the active fractions are collected. The thus obtained fractions are passed through a column of Dowex 44 (OH- form), and active substances are eluted out with water. The active fractions are again collected and concentrated to about 50 ml. The thus obtained concentrate is lyophilized, whereby about 32 g of a crude powder containing Fortimicin A is obtained. The crude powder exhibits an activity of 575 unit/mg (the activity of 1 mg of a pure product corresponds to 1000 units).
  Then 10 g of the crude powder is placed as a thin and uniform layer on 500

• Trademarks

  FORTIMICIN

• Therapeutic Function

  Antibiotic

• Allgemeine Beschreibung

  Astromicin was found in the culture broth of Micromonospora olivoasterospora by Nara et al. of Kyowa Hakko Kogyo Co. in 1976. It has a unique conformation with an acylated diamino inositol moiety different from other aminoglycoside antibiotics. Astromicin is produced with one major byproduct, fortimicin B, and several minor components.

ASTROMICIN SULFATE Upstream-Materialien And Downstream Produkte

ASTROMICIN SULFATE Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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