Unlock instant, AI-driven research and patent intelligence for your innovation.

Separation and extraction process for Mevastatin

A technology of mevastatin and fermentation broth, applied in the direction of organic chemistry, etc., can solve the problems of lowering the price of statins, low total yield of mevastatin, and increasing production cost.

Active Publication Date: 2012-12-19
LIVZON NEW NORTH RIVER PHARMA
View PDF11 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] As can be seen from the above, the present mevastatin separation and extraction process all has the problem of low total yield of mevastatin extracted from the fermentation broth, and the lower yield of mevastatin will not only cause great waste, but also cause Invisibly increase its production cost, which is not conducive to the reduction of the price of statin drugs with mevastatin as the precursor, thus increasing the economic pressure on users of such drugs

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Separation and extraction process for Mevastatin
  • Separation and extraction process for Mevastatin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Experiment A

[0047] 5L of isobutyl acetate was mixed with 5L of water, and added continuously to the mevastatin-containing fermentation broth (10L) after 0.5h. Adjust pH 9.0-9.6 with concentrated NaOH. The mixture was heated to 60°C and maintained at this temperature for 2 hours. The organic and aqueous phases were separated by countercurrent separation. Sodium lauryl sulfate was added to help emulsify the mixture upon separation.

[0048] The pH of the purified fermentation broth was adjusted to 2.0-4.5 with sulfuric acid. 5L of isobutyl acetate was continuously added to the fermentation broth, and the isobutyl acetate phase containing mevastatin was continuously separated.

[0049] The isobutyl acetate phase was concentrated to about 150 mL under vacuum. Dilute the concentrate to 800mL with NaHCO 3 washing. After washing, the concentrate was concentrated again to 150 mL. The concentrate is cooled to 0-5°C. Get mevastatin after overnight.

[0050] Experimen...

Embodiment 2

[0071] Phosphoric acid was used to adjust the pH value of 10L of fermented liquid, and the fungus residue obtained by filtering was blown dry until the water content of the fungus residue was 32%, and the filtrate was tested and then processed. Put the dried slag and toluene into the extraction tank, the ratio of toluene to slag is 6:1 (V / W), cyclization, the cyclization takes 8.5 hours, filter, wash the filter residue 3 times with toluene , and the washings were mixed with the filtrate and allowed to stand to complete the extraction. Dry the waste residue, and carry out environmental protection treatment of the waste residue and the extracted waste liquid.

[0072] The extract filtrate was distilled under reduced pressure, and toluene and water were recovered. After the reduced-pressure distillation, the temperature of the concentrated solution was lowered to 15°C, and n-hexane at the same temperature was added, kept stirring and crystallized. Filtrate, vacuumize the filter ...

Embodiment 3

[0076] 10L of fermented liquid was adjusted to pH 2.3 with phosphoric acid, the fungus residue obtained by filtration was blown dry, and the filtrate was tested and then processed. Put the dried slag and toluene into the extraction tank, the ratio of toluene to slag is 6:1 (V / W), cyclization, the cyclization takes 8.5 hours, filter, wash the filter residue 3 times with toluene , and the washings were mixed with the filtrate and allowed to stand to complete the extraction. Dry the waste residue, and carry out environmental protection treatment of the waste residue and the extracted waste liquid.

[0077] The extract filtrate was distilled under reduced pressure to recover toluene and water. After the reduced-pressure distillation was completed, the temperature of the concentrated solution was lowered to 15° C., and n-hexane at the same temperature was added, kept stirring and crystallized. Filtrate, vacuumize the filter cake, soak it with n-hexane and then dry it, and dry the ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a process for purification and extraction of Mevastatin from fermentation broth. The process is characterized in that the fermentation broth containing Mevastatin is pretreated with acid and bacterial slag is subjected to blow drying. The process provided by the invention enables a production period to be shortened, cost to be reduced and yield of a crude product of Mevastatin to be increased.

Description

technical field [0001] The invention relates to a method for isolating or purifying mevastatin or a pharmaceutically acceptable salt thereof from microbial fermentation liquid. Background technique [0002] Mevastatin (mevastatin, as shown in formula 1), also known as compactin (compactin), ML-236B, is a 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor, It was accidentally extracted from the culture medium of fungi (Penicillium Citrinum) by Biochemist Endo of Sankyo Pharmaceutical Company in Japan, and its chemical name is 2-methylbutyric acid-{1S-[1α(R), 7β, 8β(2S, 4S ), 8aβ]}-1,2,3,7,8,8a-hexahydro-7-methyl-8{2-[4-hydroxy-6-oxo-2H-tetrahydropyranyl]-B Base}-1-naphthyl ester, the specific structural formula is as follows: [0003] [0004] Mevastatin is the first generation of statins, and now it is mostly used as the precursor of pravastatin, an active statin drug. Therefore, the yield and quality of mevastatin directly affect the cost and purity of...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D309/30
Inventor 唐阳刚李敬辉张起智卢创向双
Owner LIVZON NEW NORTH RIVER PHARMA