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A tacrolimus separation and purification method

A tacrolimus, separation and purification technology, applied in the field of biopharmaceuticals, can solve the problems of drug efficacy, side effects of patients, unsatisfactory tacrolimus purity, etc., to achieve the effect of improving drug efficacy and purity

Inactive Publication Date: 2018-01-09
WUXI FORTUNE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] At present, tacrolimus is mainly prepared by fermentation, so many isomers or analogues will be produced during the fermentation process. The final purified tacrolimus is obtained by using the traditional reversed-phase resin and modified silica gel for separation and purification. The purity of crolimus is not ideal, usually only about 98%
There are still many impurities such as isomers in the purified tacrolimus, which will have a certain impact on the efficacy of the immune preparation made from tacrolimus, and may cause greater side effects to patients

Method used

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  • A tacrolimus separation and purification method
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Embodiment 1

[0027] A method for separating and purifying tacrolimus shown in this embodiment comprises the following steps:

[0028] Step (1): Prepare 250 g of tacrolimus fermentation extract with low chromatographic purity, filter it with a 0.45-micron microporous organic filter, and set aside. Among them, the chromatographic purity of the tacrolimus fermentation extract is about 60%.

[0029] Step (2): In the first set of medium-pressure chromatography equipment, chromatography silica gel is used as filler, and ethanol is used for cleaning and balancing. The particle size of the chromatographic silica gel in the step (2) is 300 mesh, and the pressure condition is 60 psi. In this example, macromolecular impurities such as polysaccharides and proteins in the low-chromatographic purity tacrolimus fermentation extract were effectively removed by the first set of medium-pressure chromatography equipment, so as to facilitate further purification operations in the later stage.

[0030] Step ...

Embodiment 2

[0038] A method for separating and purifying tacrolimus shown in this embodiment comprises the following steps:

[0039] Step (1): Prepare a tacrolimus fermentation extract with low chromatographic purity, filter it with a 0.45-micron microporous organic filter membrane, and set aside. Among them, the chromatographic purity of the tacrolimus fermentation extract is about 60%.

[0040] Step (2): In the first set of medium-pressure chromatography equipment, chromatography silica gel is used as filler, and acetone is used for cleaning and balancing. The particle size of the chromatographic silica gel in step (2) is 400 mesh, and the pressure condition is 90psi.

[0041] Step (3): The low chromatographic purity tacrolimus fermentation extract is chromatographed in the first set of medium-pressure chromatography equipment, and an organic solvent (such as: ethanol) is used for elution, and the eluate is collected, and the eluate is Rotary evaporation, dissolving with organic solve...

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Abstract

A tacrolimus separation and purification method is provided. Two medium-pressure chromatographic devices are adopted. A tacrolimus fermentation extract liquid having low chromatographic purity is adopted as a raw material. Polysaccharides, protein, and other impurities are removed through a first chromatographic column; then a solvent used for extraction is removed through a rotary evaporation process; an obtained product is dissolved again; a tacrolimus-containing eluate having a low concentration is obtained by separation through a second chromatographic column; the eluates in a plurality ofbatches are combined; and the mixture is concentrated by a nanofiltration membrane to obtain high-purity solid-state tacrolimus. Through the method, direct purification from a tacrolimus-containing fermentation solution can be achieved, the tacrolimus purity is significantly increased, and medicine effects of immunologic preparations prepared from the tacrolimus are indirectly improved.

Description

technical field [0001] The invention relates to the technical field of biopharmaceuticals, in particular to a method for separating and purifying tacrolimus. Background technique [0002] Tacrolimus, also known as FK-506 (Tacrolimus), is a macrolide immunosuppressant extracted from the metabolites of Streptomyces tsukuba by Fujisawa Pharmaceutical Company of Japan in 1982. This product has a selective inhibitory effect on T cells, mainly through inhibiting TH cells from releasing IL-2, IL-3, IFN-γ, and inhibiting the expression of IL-2R to exert its powerful immunosuppressive effect. It is suitable for preventing and treating rejection after organ transplantation, and its clinical efficacy is 100 times that of cyclosporine. [0003] At present, tacrolimus is mainly prepared by fermentation, so many isomers or analogues will be produced during the fermentation process. The final purified tacrolimus is obtained by using the traditional reversed-phase resin and modified silica...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/18
Inventor 李小刚张鹰叶骥李晓明孙益林蒋逸云
Owner WUXI FORTUNE PHARMA
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