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Process for efficiently purifying shikimic acid by utilizing continuous ion exchange technology

A technology of continuous ion exchange technology, applied in the field of efficient purification of shikimic acid using continuous ion exchange technology, can solve the problems of crossover of eluents, large fluctuations in operation between batches, large energy consumption for concentration, etc., and reduce the total amount of resin used. , the effect of enhancing market competitiveness and improving resin utilization

Active Publication Date: 2019-05-07
ZHEJIANG HISUN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] 3) This patent has no other pre-purification steps after being treated by ceramic membrane and ultrafiltration membrane, and directly uses anion exchange resin for adsorption and elution purification, which has low processing capacity of anion exchange resin, low chromatographic purity of the obtained eluent, batch Unsuitable for industrialized production due to large fluctuations in operations between operations
[0010] 4) 3-dehydroshikimic acid is an inherent impurity in the biosynthetic pathway of shikimic acid, which is similar in structure to shikimic acid. Lower resolution from shikimic acid
This process has the following disadvantages: 1. After the fermentation broth is centrifuged, the supernatant is directly concentrated under reduced pressure, which consumes a lot of energy and costs; 2. After the centrifugation, no other pre-purification steps are taken to directly purify the anion exchange resin, resulting in resin processing capacity. Very low; 3. Using twice crystallization, the total yield of the process is low, and it does not have the feasibility of industrialization
Therefore, most of the exchange groups on the anion exchange resin are bound by impurity anions, which leads to a very low effective adsorption capacity of the anion exchange resin for shikimic acid.
Moreover, these impurity anions with strong binding force also reduce the separation degree of 3-dehydroshikimic acid and shikimic acid on anion exchange resin, resulting in serious crossover of eluent and low elution yield of shikimic acid with high chromatographic purity
Poor quality eluents, causing more stress in subsequent purification steps

Method used

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  • Process for efficiently purifying shikimic acid by utilizing continuous ion exchange technology
  • Process for efficiently purifying shikimic acid by utilizing continuous ion exchange technology
  • Process for efficiently purifying shikimic acid by utilizing continuous ion exchange technology

Examples

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Effect test

Embodiment 1

[0070] Example 1: Construction of shikimic acid-producing genetically engineered bacteria E.coli HZ09-11 and preparation of shikimic acid fermentation broth

[0071] Construction and preservation of shikimic acid-producing genetically engineered bacteria E.coli HZ09-11:

[0072] Refer to the paper Shikimic Acid Production by a ModifiedStrain of E.coli (W3110.shik 1) Under Phosphate-Limited and Carbon-Limited Conditions. (Biotechnology and Bioengineering, 2005, 92 (5), 541-552.) by Louise Johansson et al. In the strain construction method disclosed, the host bacteria (strain number: CCTCC AB 209414, Escherichia coli derived from China Center for Type Culture Collection (CCTCC)) is genetically modified to obtain shikimic acid-producing genetically engineered bacteria E.coli HZ09-11 . Mix the bacterial suspension with 40% glycerol at a ratio of 1:1 and store at -20°C to obtain a glycerol tube of the working strain.

[0073] Preparation of shikimic acid fermentation broth:

[0...

Embodiment 2

[0083] Embodiment 2: the technique of extracting shikimic acid in fermented liquid

[0084] a) Solid-liquid separation: 70 L of the shikimic acid fermentation broth prepared in Example 1 was subjected to ceramic membrane microfiltration with a pore size of 50 nm. During the microfiltration process, frozen brine was used to cool down, and the feed liquid temperature was maintained at 30-35° C. Collect the fermentation filtrate. When the fermentation filtrate seeps out 36L, start to add deionized water continuously to the ceramic membrane raw material tank. unchanged), and finally collected a total of 174L of fermentation filtrate.

[0085] b) Put the 174L fermentation filtrate obtained in step a) on the column to a resin column filled with 10L of HZ001 cation exchange resin. The column effluent end is equipped with an online pH electrode and a conductivity sensor. The pH value of the liquid rises sharply until the slope of the pH value curve is > 1.5, stop loading the column, ...

Embodiment 3

[0091] Embodiment 3: the technique of extracting shikimic acid in fermented liquid

[0092]a) Solid-liquid separation: 70 L of shikimic acid fermentation broth prepared in Example 1 was subjected to ceramic membrane microfiltration with a pore size of 100 nm. During the microfiltration process, frozen brine was used to cool down, and the feed liquid temperature was maintained at 30-35° C. Collect the fermentation filtrate. When the fermentation filtrate seeps out 35L, start to add deionized water continuously to the ceramic membrane raw material tank. Collect ceramic membrane permeate 160L.

[0093] b) Put the 160L fermentation filtrate obtained in step a) on the column to a resin column filled with 13L of HZ016 cation exchange resin, the column effluent end is equipped with an online pH electrode and a conductivity sensor, and the column flow rate is 1.5BV / h. The pH value of the effluent rises sharply until the slope of the pH curve > 1.5, stop loading the column, then use 2...

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Abstract

The invention discloses a process for efficiently purifying shikimic acid by utilizing a continuous ion exchange technology, and the process comprises: carrying out solid-liquid separation to obtain afermentation filtrate, and carrying out pre-purification on the fermentation filtrate by virtue of cation exchange resin to obtain a pre-purified liquid a; and pre-purifying the pre-purified liquid athrough a continuous ion exchange system to obtain a pre-purified liquid b; and finally, carrying out fine purification and spray drying on the pre-purified liquid b to obtain the shikimic acid. Theprocess has the advantages that the process is simple and stable, continuous and automatic production can be realized, the chromatographic purity and the content of the prepared shikimic acid finishedproduct are both higher than 99%, the utilization rate of the resin is greatly improved, the total usage amount of the resin is reduced by about 80%, an eluent is not used in the pre-purification process, wastewater is greatly reduced, the production cost is greatly reduced, the market competitiveness of the product is enhanced, and the process is suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of separation and purification of fermented products, and in particular relates to a process for efficiently purifying shikimic acid by using continuous ion exchange technology. Background technique [0002] Shikimic acid (Shikimic acid, formula I) was first extracted by Eykman in 1885 from the dried ripe fruit of the star anise plant, and its chemical name is 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid , the molecular formula is C 7 h 10 o 5 , with a molecular weight of 174.15. [0003] [0004] Shikimic acid can inhibit platelet aggregation, arterial and venous thrombosis and cerebral thrombosis by affecting the metabolism of arachidonic acid. It also has anti-inflammatory and analgesic functions. A key intermediate in the synthesis of Tamiflu, a drug for the prevention and treatment of bird flu. In the past ten years, the avian influenza epidemic has continued to spread around the world, and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/42C07C51/43C07C51/47C07C62/32
Inventor 朱明新任长洪
Owner ZHEJIANG HISUN PHARMA CO LTD
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