Micronomicin

Micronomicin Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Micronomicin, formerly called sagamicin, was found in the culture broth of Micromonospora sagamiensis var. nonreducans by Kyowa Hakko Kogyo Company and Abbott Laboratories in 1974. The compound is identical with one of the minor components contained in gentamicin, gentamicin C2b, but it is produced as a single component. Its amino group at the 6 -position is methylated and is not subject to the enzymatic acetylation caused by resistant bacteria, including Pseudomonas aeruginosa. Micronomicin is less toxic than gentamicin to the renal and aural systems.

• Originator

  Sagamicin,Kyowa Hakko,Japan,1982

• Verwenden

  Gentamicin C2b is a component of Gentamicin Sulphate Complex C. Gentamicin (G360600) is an antibiotic from bacteria Micromonospora purpurea and used to treat respiratory and urinary tract, blood, bone and soft tissues infections.

• Verwenden

  Gentamicin C2b (micronomicin) is a trisaccharide pentaaminoglycoside antibiotic belonging to the gentamicin class. Gentamicin C2b was isolated from Micromonospora sagamiensis var. nonreductans by researchers at Kyowa Hakko Kogyo in 1974. Gentamicin C2b has broad activity against Gram positive and Gram negative bacteria. More recently, gentamicin C2b has been shown to induce neuromuscular blockage.

• Definition

  ChEBI: Gentamicin C2b is an aminoglycoside.

• Manufacturing Process

  A. Culturing of MK-65: In this example, Micromonospora sagamiensis MK-65 ATCC 21826 (FERM-P No. 1530) is used as the seed strain. One loopful of the seed strain is inoculated into 30 ml of a first seed medium in a 250 mlErlenmeyer flask. The first seed medium has the following composition:
  Percent Dextrin 1 Glucose 1 Peptone 0.5 Yeast extract 0.5 CaCO3(pH: 7.2 before sterilization) 0.1
  Culturing is carried out with shaking at 30°C for 5 days. 30 ml of the seed culture is then inoculated into 300 ml of a second seed medium, of the same composition as the first seed medium, in a 2 liter-Erlenmeyer flask provided with baffles. The second seed culturing is carried out with shaking at 30°C for 2 days. Then 1.5 liters of the second seed culture (corresponding to the content of 5 flasks) is inoculated into 15 liters of a third seed medium of the same composition as set forth above, in a 30 liter-glass jar fermenter. Culturing in the jar fermenter is carried out with aeration (15 liters/minute) and stirring (350 rpm) at 30°C for 2 days. Then, 15 liters of the third seed culture is inoculated into 60 liters of a fourth seed medium of the same composition as set forth above, in a 300 liter-fermenter. Culturing in the fermenter is carried out with aeration (60 liters/minute) and stirring (150 rpm) at 30°C for 2 days. Finally, 60 liters of the fourth seed culture is inoculated into 600 liters of a fermentation medium having the following composition in a 1,000 liter-fermenter.
  Percent Dextrin 5 Soybean meal 4 CaCO3 (pH: 7.2 before sterilization) 0.7
  Culturing in the fermenter is carried out with aeration (600 liters/minute) and stirring 150 rpm) at 35°C for 5 days.
  B. Isolation of crude antibiotic: After the completion of fermentation, the culture liquor is adjusted to a pH of 2.0 with 12 N sulfuric acid and stirred for 30 minutes. Then, about 10 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 8.0 with 6N sodium hydroxide and passed through a column packed with about 50 liters of a cation exchange resin, Amberlite IRC-50 (ammonia form). The active substance is adsorbed on the resin and the eluate is discarded. After washing the resin with water, the active substance is eluted out with 1N aqueous ammonia. The eluate is obtained in fractions and the activity of each of the fractions is determined against Bacillus subtilis No. 10707 by a paper disk method using an agar plate.
  Active fractions are combined and concentrated in vacuo to about 5 liters. The concentrate is then adjusted to a pH of 8.0 with 6N sulfuric acid and passed through a column packed with 1 liter of an anion exchange resin, Dowex 1X2 (OH-form). The column is washed with about 5 liters of water and the effluent and the washings containing active substance are combined and are concentrated to 1/15 by volume. The concentrate is adjusted to a pH of 10.5 with 6 N sodium hydroxide and 5 volumes of acetone is added thereto. The resultant precipitate is removed by filtration and the filtrate is concentrated to 500 ml. The concentrate is adjusted to a pH of 4.5 with 6 N sulfuric acid and 2.5 liters of methanol is added thereto. After cooling, a white precipitate is obtained. The precipitate is separated by filtration and washed with methanol. After drying in vacuo, about 300 g of white powder is obtained.
  The white powder is a mixture of the sulfate of gentamicin C1a, and the sulfate of XK-62-2, and exhibits an activity of 620 units/mg (the activity of 1 mg of pure product corresponds to 1,000 units).
  C. Isolation and purification of XK-62-2: 100 g of the white powder obtained in the above step B are placed to form a thin, uniform layer on the upper part of a 5 cm x 150 cm column packed with about 3 kg of silica gel advancely suspended in a solvent of chloroform, isopropanol and 17% aqueous ammonia(2:1:

• Therapeutic Function

  Antibiotic

• Antimicrobial activity

  Antibacterial and pharmacokinetic properties are similar to those of its precursor gentamicin C1a but it is more resistant to AAC(6′). Dosage is similar to that for gentamicin, and should be controlled by blood level determinations. It is available in Japan.

Micronomicin Upstream-Materialien And Downstream Produkte

Micronomicin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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