The way to get oxytetracycline

C12P29 - Preparation of compounds containing a naphthacene ring system, e.g. tetracycline (C12P0019000000 takes precedence);;

 

(57) Abstract:

Usage: medical industry, production of antibiotics. The essence of the invention: upon receipt of the antibiotic oxytetracycline produce cultivation of Streptomyces rimosus in a nutrient medium containing sources of nitrogen, carbon, mineral salts under conditions of aeration, mixing, regulation of the content of ammonia nitrogen and pH, while in the process of cultivation carried out dolive carbonaceous substrate in an amount sufficient to maintain the viscosity of the culture liquid at 60 100.10-3PA.with, and the first topping is produced when reaching the viscosity of the culture fluid 60.10-3PA.with.

The invention relates to the medical industry, namely the method of obtaining biologically active compounds, in particular of the antibiotic oxytetracycline.

A method of obtaining oxytetracycline [1] by cultivation of a producer in a nutrient medium containing sources of carbon, nitrogen, under conditions of aeration and mixing. However, due to increasing the viscosity of the culture liquid in the fermentation process with 10.10-3PA.to 200.10-3PA.is the deterioration of the MIA is to increase the level of antibioticaccutane.

The aim is achieved in that in the method of producing the antibiotic oxytetracycline by growing producer Str.rimosus in a nutrient medium containing sources of carbon, nitrogen, mineral salts, in the conditions of aeration and mixing is additionally adjusting the viscosity of the feed solution of the substrate in the fermentation process.

Example 1.

Vegetative seeds producer of the antibiotic oxytetracycline grown on a medium containing, by weight.

corn flour 7,0

corn extract 2,4

fish oil 0,5

soy flour 0,5

ammonium sulphate 0,6

in volume 8 of the 10% of the inoculated fermentation medium of the following composition, wt.

corn flour 14

ammonium sulphate 0,72

propanol B-400 0,1

soy flour 0,72

chalk 1,6

chloride cobalt 0,0003

The fermentation is carried out in the apparatus Ankum 2 M with a capacity of 10 L. the Initial amount together with seeds of 6.6 liters of the fermentation Process is carried out at 27 1oC, aeration 1 volume of air to 1 volume of the medium, the speed of rotation of the stirrer 600 rpm

In the course of the process control and regulate the content of ammonium nitrogen, carbohydrates, pH, and viscosity.

The viscosity of ODA is and begin feeding glucose with such speed, to viscosity values were in the range of 60 100.10-3PA.with.

When the concentration of ammonia nitrogen in the culture fluid will be reduced to 0.2 to 0.4 mg/ml, begin to apply a 25% solution of ammonium sulfate, maintaining the concentration of ammonium nitrogen in the culture fluid of 0.2 to 0.4 mg/ml While lowering the pH to 5.8 stop filing solution of ammonium sulfate and begin to regulate the pH at 5.8 to 6.0 submission of a 10% ammonia solution.

When increasing the volume of the culture fluid in the apparatus to 8 l begin daily cast of 250 to 300 ml of the culture fluid. The activity of oxytetracycline, the volume of the culture fluid is drained from the apparatus 300 h of growth was 26000 U/ml, 8 l, respectively.

The drained volume of the culture fluid during the process 2.5 l with an average activity 16400 IU/ml

Example 2.

Vegetative AMF inoculum producer of the antibiotic oxytetracycline grown in flasks, inoculated seed medium in the apparatus with a capacity of 750 litres, containing, by weight.

corn flour 7,0

corn extract 2,4

soy flour 0,5

ammonium sulfate 0,6

chalk 1,5

fish oil 0,5

and grow seeds for 24 to 30 h perelom in the amount of 200 l inoculated fermentation medium of the following composition, wt.

corn flour 14

corn extract 3,0

chalk 1,6

soy flour 0,72

ammonium sulfate 0,72

propanol B-400 0,1

chloride cobalt 0,72

The process of cultivation are in fermenters with a capacity of 3 m3when 27 1oC, overpressure -0,04 MPa, aeration 1 volume of air to 1 volume of medium per minute, the speed of the mixer 170 rpm

By reducing the content of ammonium nitrogen to 0.4 mg/ml begin filing of a 25% aqueous solution of ammonium sulfate, maintaining the concentration of ammonium nitrogen in the culture fluid of 0.2 to 0.4 mg/ml While lowering the pH to 5.8 stop filing solution of ammonium sulfate and begin to regulate the pH at 5.8 to 6.0 submission to the office of 25% ammonia solution. In the fermentation process control and regulate the content of ammonia nitrogen, pH, and viscosity.

When you reach a viscosity 60.10-3PA.with 40 to 50 h produced 1 topping 200 l (10% of the volume of the medium) of the hydrolysate of corn flour, the second and third dolive carry on the viscosity of the culture fluid, keeping it in the range of 60 100.10-3PA.with. Foam breaking exercise as in the known method: up to 100 hours as foaming produce a supply of fish oil.

is etracycline 206 h in culture liquid, performance was 18530 U/ml of 2.8 m3; 52 billion Units. 0,084 billion U/m3h, respectively.

By a known method activity values, volume, removal of the antibiotic in the culture fluid, performance 203 h growth are 19330 U/ml; 2.2 m3; 42 billion Units. 0,07 billion Units./m3h

Example 3.

The fermentation is carried out as in example 2, but in the fermentation process for foam breaking is used only propanol B-400. The use of fat as a defoamer and a carbon-containing substrate is eliminated.

The activity value of the culture fluid volume, removal of the antibiotic, performance 156 h of growth was 14000 Ed./ml 2.8 m3; eat 39,1 billion Units. performance 0,084 billion U/m3including Indicators of the biosynthesis of the prototype presented in example 2.

The way to get oxytetracycline by cultivation of Streptomyces rimosus in a nutrient medium containing sources of nitrogen, carbon, mineral salts under conditions of aeration, mixing, regulation of the content of ammonia nitrogen and pH, followed by separation of the target product, characterized in that in the process of cultivation carried out dolive carbon-containing substrate in the first topping is produced when reaching the viscosity of the culture fluid 60 10-3A pass.

 

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