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Preparation method of epothilone B molecularly imprinted polymer

A technology of epothilone and molecular imprinting, which is applied in a preparation field in the field of biochemical engineering technology, can solve the problems of high cost of separation and purification, difficulty in increasing epothilone production, and high production cost of epothilone, and achieves Increase specific adsorption, improve specific selective adsorption capacity, and reduce production costs

Inactive Publication Date: 2012-05-02
SHAANXI UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The first is that the toxicity and feedback inhibition of epothilones to the production strains make it difficult to increase the fermentation yield of epothilones. Although this difficulty has been achieved by adding macroporous adsorption resin XAD-16 to the fermentation broth However, the resin’s non-specific adsorption of nutrients in the fermentation broth has brought many new difficulties to the improvement of the yield of epothilone
The second reason for the high production cost of epothilones is that there are a large number of epothilones homologues in the product after fermentation, which leads to very high cost of separation and purification of the target product (for example: epothilone B)
[0005] Molecularly imprinted polymers are polymer materials that have specific recognition properties for specific molecules. At present, there are no research reports on epothilone molecularly imprinted polymers at home and abroad.

Method used

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  • Preparation method of epothilone B molecularly imprinted polymer
  • Preparation method of epothilone B molecularly imprinted polymer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Mix 1.0 mmol of template molecule epothilone B; 4 mmol of functional monomer methacrylic acid, 20 mmol of crosslinking agent ethylene glycol dimethacrylate and 5 ml of solvent acetonitrile:methanol (4:1 (v / v)), After standing at room temperature for 1 hour, 10 mg of initiator azobisisobutyronitrile was added. After charging, degassed by ultrasonic vibration for 10 minutes, followed by blowing nitrogen to remove oxygen for 30 minutes, sealed the tube under the condition of blowing nitrogen, polymerized in a 45°C water bath for 12 hours, and then polymerized in a 60°C water bath for 12 hours to obtain a block polymer.

[0021] After the reaction is finished, the obtained epothilone B molecularly imprinted polymer is crushed, ground and sieved. The acetone was settled three times, and freeze-dried to obtain polymer particles with a particle size of 40-60 μm.

[0022] The above-mentioned 40-60 μm polymer particles were extracted by Soxhlet extractor for 72 hours to remove ...

Embodiment 2

[0025] 1.0mmol of template molecule epothilone B; 4mmol of functional monomer methacrylic acid, 20mmol of crosslinking agent ethylene glycol dimethacrylate and 4ml of solvent acetonitrile:methanol (4:1 (v / v)) were mixed evenly, After standing at room temperature for 1 hour, 10 mg of initiator azobisisobutyronitrile was added. After charging, degassed by ultrasonic vibration for 10 minutes, followed by blowing nitrogen to remove oxygen for 30 minutes, sealed the tube under the condition of blowing nitrogen, polymerized in a 45°C water bath for 12 hours, and then polymerized in a 60°C water bath for 12 hours to obtain a block polymer.

[0026] After the reaction is finished, the obtained epothilone B molecularly imprinted polymer is crushed, ground and sieved. The acetone was settled three times, and freeze-dried to obtain polymer particles with a particle size of 40-60 μm.

[0027] The above-mentioned 40-60 μm polymer particles were extracted by Soxhlet extractor for 72 hours ...

Embodiment 3

[0030] 0.5mmol of template molecule epothilone B; 2mmol of functional monomer methacrylic acid, 10mmol of crosslinking agent ethylene glycol dimethacrylate and 3ml of solvent acetonitrile:methanol (4:1 (v / v)) were mixed evenly, After standing at room temperature for 1 hour, 5.0 mg of initiator azobisisobutyronitrile was added. After charging, degassed by ultrasonic vibration for 5 minutes, followed by blowing nitrogen to remove oxygen for 20 minutes, sealed the tube under the condition of blowing nitrogen, polymerized in a water bath at 45°C for 12 hours, and then polymerized in a water bath at 60°C for 12 hours to obtain a block polymer.

[0031] After the reaction is finished, the obtained epothilone B molecularly imprinted polymer is crushed, ground and sieved. The acetone was settled three times, and freeze-dried to obtain polymer particles with a particle size of 40-60 μm.

[0032] The above-mentioned 40-60 μm polymer particles were extracted by Soxhlet extractor for 48 ...

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Abstract

The invention discloses a preparation method of an epothilone B molecularly imprinted polymer and belongs to the technical field of chemical engineering. The preparation method comprises the following specific steps of: dissolving a template molecule (epothilone B), a functional monomer, a cross-linking agent and an initiator into a pore-foaming agent according to a certain mol ratio, wherein the pore-foaming agent can be a mixed solution of methanol and acetonitrile; after reaction, grinding and sieving the obtained product to obtain particles with the particle size being about 40-60mum; fully washing the obtained particles in a mixed solution of acetic acid and methanol according to the ratio being (1: 9)-(3:7) (v:v) so as to remove the template molecule; and freezing and drying to obtain the epothilone B molecularly imprinted polymer. The epothilone B molecularly imprinted polymer prepared by the preparation method disclosed by the invention can be used for specifically and selectively adsorbing the epothilone B and has greater application value in the production process of the epothilone B by adopting a liquid fermenting method.

Description

technical field [0001] The present invention relates to a preparation method in the technical field of biochemical engineering, in particular to a preparation method of epothilone B molecularly imprinted polymer. Background technique [0002] Epothilone B (Epothilone B) is a polyketide secondary metabolite produced by the myxobacterium Sorangium cellulosum. paclitaxel) has the same microtubule-stabilizing activity and is active against paclitaxel-resistant tumor cells. [0003] The discovery of epothilones can be traced back to extensive research work on myxobacteria in soil by microbiologists at the German National Center for Biotechnology Research (GBF) in the 1980s. In 1987, when they were looking for antifungal drugs, they discovered that a strain of myxobacteria (Sorangium cellulosum So ce90) could produce a class of macrolide compounds with weak antifungal activity, named epothilone A and B. At that time, this compound did not attract the attention of researchers. ...

Claims

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Application Information

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IPC IPC(8): C08F222/14C08F220/06C08F2/44C08J9/26
Inventor 李慧万吉龚国利王学川
Owner SHAANXI UNIV OF SCI & TECH
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