Triptorelin purification method

A purification method and sample technology, applied in the field of purification of triptorelin, can solve the problems of difficulty in achieving purity, unmentioned purity of finished products and single impurities, etc., and achieve the effects of stable and controllable process and significant social and economic benefits.

Active Publication Date: 2019-03-08
苏州天马医药集团天吉生物制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method does not mention the purity of the finished product and the single impurity situation, it is difficult to achieve the purity required for medicine

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Weigh 40mmol of triptorelin crude peptide, 56.4 grams in total, dissolve the crude peptide with 5% acetonitrile aqueous solution at 5mmol / L, stir to dissolve the sample completely, put it in a constant temperature water bath at 28°C for 90min, and filter it with a 0.45μm mixed filter membrane. The filtrate was collected and quantified by HPLC to contain 39.1 g of the target peptide.

[0032] Primary purification: chromatographic column: reversed-phase polymer filler 10μm, Column diameter and length are 50mm×250mm; mobile phase A: 0.15% phosphate buffered saline (v / v), adjust pH to 2.0 with triethylamine, mobile phase B: methanol; flow rate: 80ml / min; detection wavelength: 230nm; Loading amount: target peptide 6.6 g / needle; gradient: B% phase 37%-47%, linear elution 60min. Collect samples with a purity greater than 94% and less than 1% impurity, combine and recover samples with a purity less than 94% and greater than 70%, and purify again according to the above steps, ...

Embodiment 2

[0036]Weigh 40mmol triptorelin crude peptide, 56.4 grams in total, dissolve the crude peptide with 10% acetonitrile aqueous solution at 5mmol / L, stir to dissolve the sample completely, put it in a constant temperature water bath at 28°C for 60min, and filter it with a 0.45μm mixed filter membrane. The filtrate was collected and quantified by HPLC to contain 39.0 g of the target peptide.

[0037] Primary purification: chromatographic column: reversed-phase polymer filler 10μm, The column diameter and length are 50mm×250mm; mobile phase A: 0.15% phosphate buffered saline (v / v), adjust the pH to 2.5 with triethylamine, mobile phase B: methanol; sample loading: target peptide 6.5 g / needle; Flow rate: 80ml / min; detection wavelength: 230nm; gradient: B% phase 37%-47%, linear elution for 60min. Collect samples with a purity greater than 94% and less than 1% impurity, combine and recover samples with a purity less than 94% and greater than 70%, and purify again according to the abov...

Embodiment 3

[0041] Weigh 200mmol triptorelin crude peptide, 282.1 grams in total, dissolve the crude peptide with 5% acetonitrile aqueous solution at 5mmol / L, stir to dissolve the sample completely, put it in a 30°C constant temperature water bath for 90min, and filter it with a 0.45μm mixed filter membrane. The filtrate was collected and quantified by HPLC to contain 195.2 g of the target peptide.

[0042] Primary purification: chromatographic column: reversed-phase polymer filler 10μm, Column diameter and length are 150mm×300mm; mobile phase A: 0.15% phosphate buffered saline (v / v), adjust pH to 2.0 with triethylamine, mobile phase B: methanol; flow rate: 400ml / min; detection wavelength: 230nm; Loading amount: target peptide 19.6 g / needle; gradient: B% phase 37%-47%, linear elution for 60 minutes. Collect samples with a purity greater than 94% and less than 1% impurity, combine and recover samples with a purity less than 94% and greater than 70%, and purify again according to the abov...

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Abstract

The invention discloses a triptorelin purification method, and belongs to the technical field of purification and separation. The triptorelin purification method includes the steps of dissolving crudepeptide in an aqueous solution containing an organic solvent; taking 10 micrometers of 100 angstrom reverse-phase polymer fillers as the stationary phase, triethylamine phosphate as the phase A and methanol as the phase B to perform gradient elution; taking octadecylsilane bonded silica gel as the stationary phase, an aqueous solution of trifluoroacetic acid as the phase A and acetonitrile as thephase B to perform gradient elution; converting triptorelin into acetate, and performing lyophilizing to obtain triptorelin acetate with the purity higher than 99.9% and the single impurity less than0.02%, wherein the purification yield is higher than 80%, and the total yield is as high as 50% or more. The triptorelin purification method has the advantages that the existing problems, such as lowproduct purification and total yield and low purity of finished products, are solved, the process is stable and controllable, and the triptorelin purification method is suitable for industrial production and has significant social and economic benefits.

Description

technical field [0001] The invention relates to a purification method of triptorelin, which belongs to the technical field of separation and purification. Background technique [0002] Triptorelin, English name: Triptorelin Acetate, drug aliases Dabijia, Diferelin, etc., the amino acid sequence is: L-pyroglutamyl-L-histidyl-L-tryptophanyl-L-seryl- L-Tyrosyl-D-Tryptophanyl-L-Leucyl-L-Arginyl-L-Prolyl-Glycylamide. [0003] Triptorelin is a synthetic analogue of gonadotropin-releasing hormone. Its structural modification is to replace the sixth glycine in the natural molecular structure with D-tryptophan to make it more effective. and longer plasma half-life. Triptorelin is clinically used in the treatment of hormone-dependent prostate cancer, uterine fibroids, endometriosis, central precocious puberty, etc., and can also be used in in vitro fertilization. [0004] Chinese patent CN101357936A adopts C18 column purification, mobile phase: 0.1MNH4Ac: acetonitrile (7.5:2.5, vol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/23C07K1/16
CPCC07K7/23
Inventor 徐瑞陈维维黄保胜沈杰
Owner 苏州天马医药集团天吉生物制药有限公司
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