Preparation method for obtaining high-purity crystal form A pravastatin sodium

A technology of pravastatin sodium and pravastatin, which is applied in the field of preparation of high-purity crystal form A pravastatin sodium, can solve the problems of unsuitable drug production, high production cost, and difficult solvent recovery, etc., and facilitate industrial scale promotion Application, low impurity content, stable process effect

Active Publication Date: 2020-04-17
GUANGDONG BLUE TREASURE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disclosed preparation process of crystal form A of pravastatin sodium either uses a mixed solvent, which is difficult to recover and has high production costs; or is highly toxic and unsuitable for drug production; or has high yield but low purity

Method used

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  • Preparation method for obtaining high-purity crystal form A pravastatin sodium
  • Preparation method for obtaining high-purity crystal form A pravastatin sodium
  • Preparation method for obtaining high-purity crystal form A pravastatin sodium

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Effect test

Embodiment 1

[0032] Embodiment 1, a kind of preparation method that obtains high-purity A crystal form pravastatin sodium

[0033] Include the following steps:

[0034] S1) 2300ml of fermented culture fluid containing pravastatin is filtered through a plate frame and the filtrate is collected, the filtrate is 2000ml, adjusted to pH 4.7, extracted with 2000ml of ethyl acetate to obtain the extract;

[0035] S2) Heat the extract in step S1 to reflux for 2h, cool to room temperature, filter with diatomaceous earth, and wash with 500ml, 1% sodium carbonate aqueous solution, the solution after washing is not higher than 50°C and concentrated to 300ml under reduced pressure, and cool down Crystallize at 12°C, filter, and dry under reduced pressure to obtain 22 g of pravastatin lactone crystals;

[0036] S3) Dissolve 22g of pravastatin lactone crystals in step S2 with 220ml of methyl isobutyl ketone at 60°C, add sodium carbonate aqueous solution to wash and stir at room temperature for 1.5h, a...

Embodiment 2

[0039] Embodiment 2, a kind of preparation method that obtains high-purity A crystal form pravastatin sodium

[0040] Include the following steps:

[0041] S1) 2300ml of fermentation broth containing pravastatin was filtered through a plate and frame to collect the filtrate, the filtrate was 2000ml, adjusted to pH 4.5, and extracted with 2000ml of isobutyl acetate to obtain the extract;

[0042] S2) Heat the extract in step S1 to reflux for 1.5h, cool to room temperature, filter with diatomaceous earth, and wash with 500ml, 1.5% sodium carbonate aqueous solution, the solution after washing is not higher than 50°C and concentrated to 300ml under reduced pressure, Cool down to 12°C to crystallize, filter, and dry under reduced pressure to obtain 23 g of pravastatin lactone crystals;

[0043]S3) Dissolve 23 g of pravastatin lactone crystals in step S2 with 345 ml of methyl isobutyl ketone at 50° C., add aqueous sodium carbonate to wash and stir at room temperature for 1.5 h, a...

Embodiment 3

[0046] Embodiment 3, a kind of preparation method that obtains high-purity A crystal form pravastatin sodium

[0047] Include the following steps:

[0048] S1) 2300ml of fermentation broth containing pravastatin was filtered through a plate and frame to collect the filtrate, the filtrate was 2000ml, adjusted to pH 4.5, and extracted with 2000ml of ethyl acetate to obtain the extract;

[0049] S2) Heat the extract in step S1 to reflux for 2h, cool to room temperature, filter with diatomaceous earth, and wash with 500ml, 1% sodium carbonate aqueous solution, the solution after washing is not higher than 50°C and concentrated to 300ml under reduced pressure, and cool down Crystallize at 12°C, filter, and dry under reduced pressure to obtain 22 g of pravastatin lactone crystals;

[0050] S3) Dissolve 22 g of pravastatin lactone crystals in step S2 with 330 ml of methyl isobutyl ketone at 50° C., add aqueous sodium carbonate to wash and stir at room temperature for 2 h, add dilu...

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Abstract

The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method for obtaining high-purity crystal form A pravastatin sodium. The preparation method of obtaining the high-purity crystal form A pravastatin sodium comprises the following steps: filtering a fermentation culture solution containing pravastatin by a plate frame, collecting filtrate,adjusting the pH value to be less than 5.0, and extracting by using an extracting agent to obtain an extracting solution; preparing a pravastatin lactone crystal; converting the pravastatin lactone crystal into a pravastatin amine salt wet solid; dissolving with methyl isobutyl ketone, adding a phosphate buffer solution, stirring, removing a water layer, adding purified water for washing, and discarding the water layer to obtain a washing solution; and adding a sodium hydroxide solution, stirring at room temperature in a vacuum state, cooling, crystallizing, filtering and drying to obtain theproduct. The crystal form A pravastatin sodium can be directionally prepared, the yield is good, the impurity content is low, the safety is high, the preparation method is stable in process, simple and easy to control, and industrial large-scale popularization and application are facilitated.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a preparation method for obtaining high-purity crystal form A pravastatin sodium. Background technique [0002] Pravastatin Sodium (Pravastatin Sodium), CAS No. 81131-70-6, is a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-COA reductase) inhibitor, and its structural formula is as formula I. [0003] [0004] By inhibiting the synthesis of cholesterol in the human body, pravastatin sodium can effectively reduce the content of total cholesterol, low-density lipoprotein and triglyceride in serum, and increase the content of high-density lipoprotein. It was originally used to treat hyperlipidemia and familial hyperlipidemia cholesterol. In addition, pravastatin sodium can also slow down the development of atherosclerosis, reduce the occurrence of coronary atherosclerotic lesions and clinical cardiovascular events, and at the same time, some studi...

Claims

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Application Information

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IPC IPC(8): C07C69/732C07C67/52C07C67/48
CPCC07B2200/13C07C67/48C07C67/52C07C69/732
Inventor 叶家雄潘京方锐旋石友仁陈继敏
Owner GUANGDONG BLUE TREASURE PHARMA
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