Novel fermentation reducing method for contraceptive intermediate

An intermediate and new method technology, applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of low reduction efficiency, production cycle, material consumption and energy consumption, unsatisfactory product yield, etc., to achieve yield improvement and process The effect of the simple, simplified approach

Inactive Publication Date: 2013-03-13
WUHAN TITON BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This process needs to go through steps such as seed selection, mutagenesis, constant temperature cultivation, primary, secondary, and tertiary seed fermentation, mycelium preparation, and fermentation reduction. It takes 12-15 days, and the reduction efficiency is low, requiring 10 times the reduced substrate. Great excess of mycelium
Obviously, this method is unsatisfactory in terms of production cycle, material consumption, energy consumption, product yield, etc.

Method used

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  • Novel fermentation reducing method for contraceptive intermediate
  • Novel fermentation reducing method for contraceptive intermediate
  • Novel fermentation reducing method for contraceptive intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Add 600ml of sterilized water to a 2000ml Erlenmeyer flask, add 10g of sucrose, 120g of dry Saccharomyces cerevisiae, tie the mouth with seven layers of clean gauze, place it in a constant temperature water bath at 30°C for 2 hours, take a sample on a counting plate and count it under a microscope, the number of bacteria Up to 8×10 27 / cm 2 When above, the activation is completed. Add 3000ml of water into the 5L fermenter, heat the jacket to 121°C by introducing 0.3Mpa steam into the jacket and keep it warm for 30 minutes, then cool down to 29°C. Add the activated broth. Weigh 50g of the condensate, dissolve it with 150ml of ethanol at 60°C, and slowly drop it into the fermenter. After the addition is complete, add 2ml of sorbitol. Set the temperature of the fermenter to 29°C, and the air flow rate to 5L / min. After 96 hours of fermentation, take a sample and spot the plate. When the raw material spots completely disappear, the fermentation conversion ends. Use a 300...

Embodiment 2

[0030] Add 600ml of sterilized water to a 2000ml Erlenmeyer flask, add 15g of glucose, 100g of dry Saccharomyces cerevisiae, tie the mouth with seven layers of clean gauze, place it in a constant temperature water bath at 30°C for 3 hours, take a sample on a counting plate and count it under a microscope, the number of bacteria Up to 8×10 27 / cm 2 When above, the activation is completed. Add 3000ml of water into the 5L fermenter, heat the jacket to 121°C by introducing 0.3Mpa steam into the jacket and keep it warm for 30 minutes, then cool down to 29°C. Add the activated broth. Weigh 50g of the condensate, dissolve it with 150ml of ethanol at 60°C, and slowly drop it into the fermenter. After the addition is complete, add 2ml of mannitol. Set the temperature of the fermenter to 29°C, and the air flow rate to 5L / min. After 96 hours of fermentation, take a sample and spot the plate. When the raw material spots completely disappear, the fermentation conversion ends. Use a 300...

Embodiment 3

[0032] Add 600ml of sterilized water to a 2000ml Erlenmeyer flask, add 15g of maltose, 120g of dry Saccharomyces cerevisiae, tie the mouth with seven layers of clean gauze, place it in a constant temperature water bath at 30°C for 5 hours, take a sample on a counting plate and count it under a microscope, the number of bacteria Up to 8×10 27 / cm 2 When above, the activation is completed. Add 3000ml of water into the 5L fermenter, heat the jacket to 121°C by introducing 0.3Mpa steam into the jacket and keep it warm for 30 minutes, then cool down to 29°C. Add the activated broth. Weigh 50g of the condensate, dissolve it with 150ml of ethanol at 60°C, and slowly drop it into the fermenter. After the addition is complete, add 2ml of mannitol. Set the temperature of the fermenter to 29°C, and the air flow rate to 5L / min. After 96 hours of fermentation, take a sample and spot the plate. When the raw material spots completely disappear, the fermentation conversion ends. Use a 300...

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Abstract

The invention relates to a novel fermentation reducing method for midbody hydroxide D-18-methyl-3-methoxyl-8,14-open loop-delta1,3,5(10),9(11)-estratetraenol-17-beta-alcohol-14-ketone of emergency contraceptive levonorgestrel. The method is characterized by adopting dry brewing yeast as a strain to ferment and reduce a levonorgestrel midbody condensate to obtain the midbody hydroxide. The method is easy to control the fermenting process, is easy to maintain the activity of the strain, reduces the production cycle, has high product yield and stable quality and is suitable for mass production.

Description

technical field [0001] The present invention relates to the synthesis of pharmaceutical intermediates, specifically the intermediate of the contraceptive drug levonorgestrel--D-18-methyl-3-methoxy-8,14-ring-opening-Δ1,3,5( 10), a new method for the fermentative reduction of 9(11)-estradiene-17-β-ol-14-one. Background technique [0002] Levonorgestrel: (L-(-)17a-ethynyl-17B-hydroxy-18-methylestr-4-en-3-one, English name Levonorgestre, CAS No. 797-63-7) is long Effective estrogen, absorbed through the gastrointestinal tract after oral administration, stored in adipose tissue, slowly releases ethinyl estradiol, inhibits ovarian ovulation by inhibiting the hypothalamic-pituitary-ovarian axis, and achieves long-term contraceptive effect. Progesterone is compatible with it. It has a synergistic effect on ovulation suppression and is currently a widely used oral contraceptive. Hydroxide D-18-methyl-3-methoxy-8,14-cyclo-Δ1,3,5(10),9(11)-estradien-17-β-ol-14-one It is an important...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P7/38C12R1/865
Inventor 桂厚瑛陈世扬周秋名胡新明
Owner WUHAN TITON BIOTECH
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