Method for purifying lipstatin

A purification method, the technology of riprex, which is applied in the field of riprestatin purification, can solve the problems of health hazards of operators, large loss of target products, and many steps in the extraction process, and achieve high extraction rate, low cost, and few times Effect

Inactive Publication Date: 2012-07-11
PEKING UNIV FOUNDER GRP CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, the separation and extraction process of liprestatin for microbial biosynthesis mainly adopts the organic solvent extraction method, which has the following disadvantages: 1. A large amount of acetone, ethyl acetate and more expensive n-hexane, etc. are used in the separation and extraction process Organic solvents will produce a large amount of toxic and harmful substances such as waste water and waste gas during the production process, which will pollute the environment and be toxic to the health of operators; 2. The process route is relatively complicated, and there are many steps in the extraction process. Degradation is easy to occur after a long time, and there are many technical requirements for the operation process point; 3. The loss of the target product is large and the yield is low, so the production cost is high; 4. The purity of the finished product is low; 5. The finished product has organic solvent residues, which affects the quality of the finished product

Method used

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Examples

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Effect test

Embodiment 1

[0180] When the fermentation broth is directly spray-dried, a centrifugal nozzle spray dryer is used. The gas inlet temperature of the spray dryer is controlled at 40°C, the gas outlet temperature is controlled at 35°C, the temperature of the material in the tower is kept at 40°C, and the pressure in the tower is kept at 250kPa to obtain solid fermented dry bacteria powder with a particle size of 50 mesh.

[0181] Put the above fine powder into supercritical CO 2 In the extraction kettle, adjust the extraction temperature, pressure, time, control CO 2 Flow rate for extraction, wherein: extraction kettle temperature 35°C, pressure 40.0MPa, time 4h, CO 2 The flow rate is 30L / h. The entrainer ethanol (the ratio of the volume of the entrainer to the weight of the fine powder is 5:1 (L:Kg)) was added to the extraction kettle, and its flow rate was set at 4 L / h. Then set the separation temperature of the first separation tank to 30° C. and the separation pressure to 8 MPa for the...

Embodiment 2

[0190] Spray-dry the fermentation broth directly using a centrifugal nozzle spray dryer. The gas inlet temperature of the spray dryer is controlled at 60°C, the gas outlet temperature is controlled at 50°C, the temperature of the material in the tower is kept at 55°C, and the pressure in the tower is kept at 350kPa , to obtain solid fermented and dried bacteria powder with a particle size of 80 mesh.

[0191] Put the above fine powder into supercritical CO 2 In the extraction kettle, adjust the extraction temperature, pressure, time, control CO 2 Flow rate for extraction, wherein: extraction kettle temperature 60°C, pressure 20.0MPa, time 2h, CO 2 The flow rate is 10L / h. The entrainer ethanol (the ratio of the volume of the entrainer to the weight of the fine powder is 3:1 (L:Kg)) was added into the extraction kettle, and its flow rate was set at 2 L / h. Then set the separation temperature of the first separation tank to 50° C. and the separation pressure to 5.5 MPa for the ...

Embodiment 3

[0200] The fermentation liquid is directly spray-dried using a centrifugal nozzle spray dryer. The gas inlet temperature of the spray dryer is controlled at 50°C, the gas outlet temperature is controlled at 40°C, the temperature of the material in the tower is kept at 45°C, and the pressure inside the tower is kept at 300kPa , to obtain solid fermented and dried bacteria powder with a particle size of 40 mesh.

[0201] Put the above fine powder into supercritical CO 2 In the extraction kettle, adjust the extraction temperature, pressure, time, control CO 2 Flow rate for extraction, wherein: the temperature of the extraction kettle is 40°C, the pressure is 30.0MPa, the time is 3h, CO 2 The flow rate is 30L / h. The entrainer ethanol (the ratio of the volume of the entrainer to the weight of the fine powder is 3:1 (L:Kg)) was added into the extraction kettle, and its flow rate was set at 2 L / h. Then set the separation temperature of the first separation tank to 40° C. and the s...

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Abstract

The invention provides a method for purifying lipstatin. The method comprises the following steps of: carrying out extraction on a solid mixture containing the lipstatin by using supercritical CO2 fluid, and then, purifying an obtained lipstatin extract to obtain the lipstatin. The method provided by the invention has the characteristics of high efficiency, environment-friendliness, simple process, high purity of finished products, high yield and the like.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to a method for purifying liprestatin. Background technique [0002] Lipstatin is a metabolite of Streptomyces toxytricini, which can selectively inhibit the activity of pancreatic lipase in the gastrointestinal tract and reduce the decomposition and absorption of fat. Its structural formula is shown in formula I. Its tetrahydro derivative orlistat (orlistat) has been successfully developed by Roche Inc. (Roche lnc.) 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. Therefore, the production of riprestatin by fermentation has attracted much attention. [0003] [0004] The production process of liprestatin through microbial biosynthesis mainly includes the following steps: the microbial fermentation broth is directly crushed by ultrasonic waves, extracted with an organic solvent, and then concen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/12
CPCY02P20/54
Inventor 赵德岳光易昆何晶
Owner PEKING UNIV FOUNDER GRP CO LTD
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