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Rifamycin

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Rifamycin

  1. 1. Rifamycin
  2. 2.  It is a new group of antibiotics obtained from  Nocardia mediterranea  Sterptomyces sp  Micromonospora locustis. Substances of Rifamycin:  The isolated product has five active substances.  Rifamycin A,B,C,D and E.
  3. 3.  Rifamycin B is the most active of all . It is spontaneously transforms to more active products like rifamycin O,S and SV. These are microbiologically active.  In vivo Rifamycin SV shows good activity , tolerability and solubility properties and it treats infection from gram positive bacteria
  4. 4.  Stock Cultures of Nocardia mediterranea is maintained insealed ampoules in lyophilized state.  Frozen vegetative mycelium of selected high producing colonies in small vials at a low temperature are highly stale over a long period of storage.
  5. 5.  Vegetative Medium includes:  Peanut meal (25g/l)  Soyabean Meal (10g/l)  Ammonium sulphate (10g/l)  Propylene Glycol (5g/l)  Glucose (110g/l)  Fish Meal (20-40g/l)
  6. 6.  Best yield can be obtained when 5% inoculum of a preculture grown for 24 hours is used in aerated fermenters at 28 C  It give a yeild of 6-7 g/l  During fermentation N.mediterranea has high oxygen requirements in a definite period of growth production cycle.  An air flow ranging from 0.8-1.5 l/min is essential.
  7. 7.  It is carried out in conventional bioreactors of 20-100 m3 volume.  It is equiped with turbine , stirrers , baffles , air ring spargers and heating-cooling systems,  In a fermenter. Consumption of glucose , growth of mycelium and production of antibiotic occur at the same time.  At initial stages of growth , consumption of glucose and nitrogen is slow , however , it becomes very fast when mycelial growth starts.
  8. 8.  The demand of oxygen is also very high at this stage .  Metabolic activity of mycelium changes the initial pH 6.2-6.4 to 6.6-6.7 , later it decreases to 5.5-5.7 .pH again rises slowly until the end of fermentation and optimal pH 6.2-6.4  The fermentation lasts for 300 hrs
  9. 9.  Purification of Broth after harvest is done at pH 7.5-8.0.  The filterate is acidified (pH 2.0)  Extraction of the product is carried with choloform , Re-extraction from chloroform is done in phosphate buffer of pH 8 followed by acidification of the aqueous solution and extraction with ethyl acetate from which it crystallizes

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