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Method for preparing immunosuppressant sirolimus

A technology of immunosuppressant sirolimus, which is applied in the field of preparation of the separation and purification of immunosuppressant sirolimus, can solve the problem that the quality standard of sirolimus cannot be met, the product yield cannot reach 70%, The purity of the product cannot reach 99%, and it can achieve the effects of easy decolorization and impurity removal, improved clarity and quality, and low toxicity

Inactive Publication Date: 2018-07-06
TIANJIN LINGSHI BIOTECH DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Foreign Wyeth company patent 200680006609.3 reports a method for purifying rapamycin (sirolimus), which mainly uses chemical methods to purify sirolimus. This method uses a lot of related drugs, which has high toxicity and high product purity. It can’t reach 99%, the product yield can’t reach 70%, and the ratio of trans and cis sirolimus is 3:1, basically can’t meet the quality standard of medicinal sirolimus

Method used

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  • Method for preparing immunosuppressant sirolimus
  • Method for preparing immunosuppressant sirolimus
  • Method for preparing immunosuppressant sirolimus

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Firstly, 10 L of sirolimus fermentation broth with a fermentation unit of 556 ug / mL was taken, and the sirolimus fermentation broth was subjected to vacuum filtration to separate solid and liquid from the sirolimus fermentation broth to obtain 2.76 kg of mycelia. Add 6.0 L of 95% ethanol solution to the mycelia, soak and stir for 1 hour, then vacuum filter the solution, and collect the sirolimus extract. Then dilute the above-mentioned sirolimus extract with water to the ethanol volume percent concentration is 30%, this diluted extract is decolorized by the LX-900 macroporous decolorizing resin column with a loading capacity of 500mL, the decolorized solution of gained Then import the XF-800 macroporous adsorption resin column for adsorption, the resin loading capacity of the macroporous adsorption resin column used is 500mL, and the flow rate of import is 550mL / h. Then the XF-800 resin column adsorbed with sirolimus was first washed with 1100mL volume concentration of ...

Embodiment 2

[0037] In this example, 30 L of sirolimus fermentation broth with a fermentation unit of 582 ug / mL was firstly taken, and the sirolimus fermentation broth was subjected to vacuum filtration to separate solid and liquid from the sirolimus fermentation broth to obtain 9.71 kg of mycelium . Add 29.5 L of 85% isopropanone to the above-mentioned mycelia, soak and stir for 1 hour, then vacuum filter the solution, and collect the sirolimus extract. The above-mentioned sirolimus extract is then diluted with water to a volume percent concentration of isopropanone of 25%, and this diluted extract is decolorized by the LSA-700 macroporous decolorizing resin column with a loading capacity of 2000mL, and the decolorized The liquid is then introduced into the HZ-816 macroporous adsorption resin column for adsorption. The resin loading capacity of the macroporous adsorption resin column used is 2000mL, and the flow rate of the decolorization solution is 3000mL / h. Then the HZ-816 resin column ...

Embodiment 3

[0040] In this example, 50 L of sirolimus fermentation broth with a fermentation unit of 518 ug / mL was firstly taken, and the sirolimus fermentation broth was subjected to vacuum filtration to separate solid and liquid from the sirolimus fermentation broth to obtain 16.45 kg of mycelium . Add 65 L of 90% methanol to the above mycelia, soak and stir for 1 hour, then vacuum filter the solution, and collect the sirolimus extract. The above-mentioned sirolimus extract is then diluted with water to a methanol volume percentage of 40%, and this diluted extract is decolorized by a LX-900 macroporous decolorizing resin column with a loading capacity of 2500mL, and the decolorized solution of gained Then import the D101 macroporous adsorption resin column for adsorption. The resin loading capacity of the macroporous adsorption resin column used is 2500mL, and the flow rate of the decolorization solution is 3750mL / h. Then the D101 resin column adsorbed with sirolimus was first washed w...

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Abstract

The invention relates to a method for preparing an immunosuppressant sirolimus. The method comprises the following steps: decolorizing a sirolimus mycelium extract by macro-porous decolorizing resin,introducing the obtained decolorized sirolimus solution into a macro-porous adsorption resin column, performing adsorption and desorption, concentrating the obtained desorbed solution to obtain sirolimus-containing crude extract, dissolving the crude extract in a polar solvent, performing chromatographic separation on the obtained crude extract solution by using polymer nano-spheres, and performing concentrating, crystallization and drying to obtain highly-pure sirolimus. The method for preparing highly-pure sirolimus has the advantages of simple process, reliable quality, high yield reaching70% or more, less solvent consumption, and suitableness for the industrial large-scale production of a medicinal-grade sirolimus raw material.

Description

technical field [0001] The third invention belongs to the technical field of industrial microorganisms, and relates to a preparation method of pharmaceutical raw materials, in particular to a preparation method of separating and purifying the immunosuppressant sirolimus from fermented mycelium. Background technique [0002] Sirolimus, also known as rapamycin (rapamycin), is a lipophilic nitrogen-containing 36-membered macrolide antibiotic naturally produced from Streptomyes hygroscopicus, with a molecular formula of C51H79N013, The molecular weight is 914.17, and the structural formula is as follows: [0003] [0004] Sirolimus is a white crystal with a melting point of 183-184°C and an optical rotation of -147°--157° (c=1.02, chloroform). Soluble in methanol, ethanol, acetone, ethyl acetate, chloroform or ether, hardly soluble in hexane or petroleum ether, insoluble in water. [0005] The mechanism of sirolimus as an immunosuppressant is that it can block the late reac...

Claims

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Application Information

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IPC IPC(8): C07D498/18
CPCC07D498/18
Inventor 闻建华闻铭远傅红
Owner TIANJIN LINGSHI BIOTECH DEV CO LTD
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