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New process for separating and extracting lipstatin from stretomyces toxytricini fermentation liquor

A technology of Streptomyces toxin and fermentation broth, which is applied in the direction of organic chemistry, etc., can solve the problems of low production efficiency, many hidden dangers in safety production, and increased energy consumption.

Inactive Publication Date: 2010-11-17
ARGUS PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In short, the existing process has low production efficiency, high labor intensity, large solvent consumption, and subsequent solvent recovery process, which increases energy consumption; moreover, the production environment is harsh and there are many hidden dangers in production safety.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Take 45L of pilot test fermentation broth, with a solid content of 14%. (with 0.6% riprestatin). The fermented liquid is adjusted with sulfuric acid, fed while stirring, and the pH is adjusted to about 2.5-4.5. 30.6L (solid content: 22%) of the concentrated solution obtained by the separator enters the centrifugal spray drying system. Drying conditions: the inlet air temperature is 160°C, the outlet air temperature is 85°C, and 3012g of dry powder with a moisture content of 5% is obtained. The dry powder was added into 9036ml of acetone at a weight-to-volume ratio of 1:3, stirred at 120 rpm for 1 hour, and centrifuged to obtain 8200ml of leaching liquid (liprestatin content 251.13g, recovery rate 93%). The film was vacuum-concentrated to 2050ml at 40°C (recovering acetone), 1025ml of heptane was added, extracted at room temperature, and vacuum-concentrated until no heptane condensed out to obtain 493.2g of concentrated paste, and the recovery rate of riprestatin was 8...

Embodiment 2

[0023] Take 45L of pilot test fermentation broth, with a solid content of 15%. (containing 0.58% riprestatin). The fermentation broth was adjusted with sulfuric acid to adjust the pH to about 2.5-4.5. 30.2L of concentrated liquid was obtained by separating with a separator. (solid content 21%), enter the centrifugal spray drying system. Drying conditions: air inlet 150°C, air outlet 80°C. 3097 g of dry powder with a moisture content of 6.2% was obtained. The dry powder was extracted by adding 9291 ml of ethanol in two portions according to the weight-to-volume ratio of 1:3, and stirred at 120 rpm for 1 h. After centrifugal filtration, 8.29 L of extract was obtained twice (the content of liprestatin was 248.92 g, and the recovery rate was 96%). Concentrate the film in vacuum at 40°C to 2.1L (ethanol is recovered), add 1.0L of heptane, and extract at room temperature. The heptane extract is concentrated in vacuum until no heptane condenses out to obtain a concentrated paste...

Embodiment 3

[0025] Take 42L of pilot test fermentation broth, with a solid content of 14% (containing 0.57% liprestatin). The fermentation broth was adjusted with sulfuric acid to adjust the pH to about 2.5-4.5. 29.3L of concentrated liquid was obtained by separation with a separator. Enter the centrifugal spray drying system. Drying conditions: air inlet 140°C, air outlet 80°C. 2895 g of dry powder with a moisture content of 6.8% was obtained. Add the dry powder to 8.7L of ethanol for extraction according to the weight-to-volume ratio of 1:3, and stir at 120rpm for 1h. After centrifugal filtration, 7.790 L of extract was obtained (the content of riprestatin was 231.4 g, and the recovery rate was 97%). The film was concentrated in vacuum at 40°C to 1.940L (ethanol was recovered), 970ml of heptane was added, extracted at room temperature, and concentrated in vacuum until no heptane condensed out to obtain 457.8g of concentrated paste, and the total recovery of riprestatin was 84%.

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Abstract

The invention discloses a new process for separating and extracting lipstatin from stretomyces toxytricini fermentation liquor. The process mainly comprises the following steps of: pretreating fermentation liquor, pre-concentrating the fermentation liquor, drying, extracting fungi residue with a solvent and performing solid-liquid separation on the fungi residue, concentrating the extract, and the like. The overall yield (based on the total lipstatin content of the fermentation liquor) of the lipstatin is up to more than 80 percent.

Description

technical field [0001] The invention relates to a method for extracting intracellular products from fermentation broth, in particular to a method for separating and extracting riprestatin from fermentation broth of Streptomyces toxin. Background technique [0002] Liprestatin is a metabolite of Streptomyces toxin, which can selectively inhibit the activity of pancreatic lipase in the gastrointestinal tract and reduce the decomposition and absorption of fat. Its tetrahydro derivative orlistat has been successfully developed by Roche as a weight loss drug Xenical, which is currently the only drug for the treatment of obesity marketed as a non-central nervous system effect. [0003] The main disadvantages of the traditional fermentation broth treatment methods are as follows: [0004] Solid-liquid two-phase separation is difficult. Streptomyces toxins fermented broth is highly viscous and contains a certain amount of oily substances; at the same time, the PMV content is as hi...

Claims

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Application Information

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IPC IPC(8): C07D305/12
Inventor 彭滢张虓
Owner ARGUS PHARMA
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