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Method for extracting and purifying lovastatin

A lovastatin extraction technology, applied in the field of medicine, can solve problems such as poor solubility, and achieve the effects of recovery, solution clarification, and elimination of emulsification

Inactive Publication Date: 2012-02-08
PEKING UNIV FOUNDER GRP CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] The object of the present invention is to provide a method for extracting and purifying lovastatin from a fermented liquid rich in lovastatin, while solving the emulsification problem in lovastatin extraction and improving the yield, the material purification in the intermediate process is strengthened, Improve the quality of finished products, solve the common problem of poor solubility of lovastatin products, and improve the solubility of lovastatin products in acetone, chloroform, and methanol

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Fermentation broth 10L, lovastatin unit 8458u / ml, adjusted to pH 1.5 with 5mol / L HCl, stirred and sedimented for 1 hour, filtered, collected fungus residue, added 2.5L butyl ester to the fungus residue, heated at 55°C Stir under the conditions to extract the bacteria residue for 3 hours, separate, collect the extract, keep it warm at 30°C, add 500ml 0.5mol / L NaOH to stir and wash for 30 minutes, let stand for 15 minutes to remove the water phase, add 500ml 0.5mol / L HCl to the organic phase, Stir and wash for 30 minutes, let stand for 15 minutes to remove the water phase, add 500ml deionized water to the organic phase, stir and wash for 30 minutes, let stand for 15 minutes to remove the water phase, and vacuum concentrate the organic phase (temperature 65-70°C, vacuum degree less than 0.08 MPa) to a volume of about 300ml, cooled to 12°C, incubated for 3 hours, centrifuged and dried to obtain 71g of crude product.

[0028] Add 250ml of ethanol to 71g of the crude product,...

Embodiment 2

[0030] Fermentation broth 10L, lovastatin unit 7850u / ml, adjusted to pH 1.0 with 5mol / L HCl, stirred and sedimented for 1 hour, filtered, collected fungus residue, added 2.5L butyl ester to the fungus residue, at 54°C Stir and extract the bacteria residue for 3 hours, separate, collect the extract, keep it warm at 30°C, add 500ml 0.5mol / L NaOH, stir and wash for 30 minutes, let stand for 15 minutes to remove the water phase, add 500ml 0.5mol / L HCl to the organic phase, stir and wash 30 minutes, stand still for 15 minutes to remove the water phase, add 500ml deionized water to the organic phase, stir and wash for 30 minutes, let stand for 15 minutes to remove the water phase, and vacuum concentrate the organic phase (temperature 65-70°C, vacuum degree less than 0.08MPa) To a volume of about 280ml, the temperature was lowered to 14°C, kept for 3 hours, centrifuged and dried to obtain 70g of crude product.

[0031] Add 210ml of ethanol to 70g of the crude product, dissolve it at ...

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PUM

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Abstract

The invention discloses a method for extracting and purifying lovastatin. The method comprises the following steps of: acidizing the pH of a fermentation liquor for producing lovastatin to 1-3; filtering or centrifugally separating; collecting bacterium slags; extracting the bacterium slags with an organic solvent; washing an extracting solution with an alkaline aqueous solution, an acid aqueous solution and deionized water in sequence; concentrating the washed extracting solution, and crystalizing; separating and drying the crystal to obtain a crude product; and recrystallizing the crude product to obtain purified lovastatin. Due to the adoption of the method, the problem of emulsion during the extraction of lovastatin is solved, and the dissolubility of a lovastatin product in acetone, chloroform and methanol is increased.

Description

technical field [0001] The invention relates to a preparation method of a crude drug, in particular to a method for extracting and refining lovastatin from a fermentation broth, and belongs to the field of medicine. Background technique [0002] Lovastatin is a cholesterol-lowering drug derived from microbial hydroxymethylglutaryl-CoA reductase inhibitors. Because of its clear mechanism of action and remarkable clinical efficacy, it is currently an important clinical drug for the prevention and treatment of cardiovascular and cerebrovascular diseases. Lovastatin is a secondary metabolite of fungi. The main industrially produced bacteria are Aspergillus terreus, Penicillium citrinum and Monascus ruber. The existing methods for extracting and preparing lovastatin are mainly The fermentation liquid is heated, alkalized and filtered, and then the filtrate is extracted or the filtrate is extracted by resin exchange. [0003] The lovastatin extraction method described in U.S. Pat...

Claims

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Application Information

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IPC IPC(8): C07D309/30
Inventor 李华德何勇崴张新许
Owner PEKING UNIV FOUNDER GRP CO LTD
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