Purification method of semaglutide

A purification method and crude peptide technology, which is applied in the field of separation and purification of semaglutide, can solve the problems of unstable dissolution method of crude peptide samples, unclear removal of specific impurities, and low purification yield, so as to increase the solubility, Avoid clogging with equipment and improve the separation effect

Active Publication Date: 2021-01-05
深圳深创生物药业有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The existing purification methods have problems such as unstable dissolution of crud...

Method used

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  • Purification method of semaglutide
  • Purification method of semaglutide
  • Purification method of semaglutide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Crude Peptide Pretreatment

[0049] Dissolution buffer preparation: Measure 2 mL of phosphoric acid and pour it into 750 mL of water, adjust the pH to 8.0 with triethylamine, add 200 mL of acetonitrile, and dilute to 1 L with water. Take 1 L of the prepared dissolution buffer, add 30 g of crude peptide, stir ultrasonically to completely dissolve the sample, filter it with a 0.22 μm organic filter membrane, and collect the filtrate.

Embodiment 2

[0050] Embodiment 2 first step purification

[0051] Purification conditions: chromatographic column: a chromatographic column with octaalkylsilane bonded silica gel as the stationary phase, and the diameter and length of the column are: 5cm×25cm. Mobile phase: Phase A: aqueous solution containing 0.2% phosphoric acid (v / v) and 20% acetonitrile (v / v), adjusted to pH 8.0 with triethylamine; phase B: acetonitrile, flow rate: 80mL / min, gradient: B% : 20%-40%, linear gradient elution 60min; detection wavelength: 230nm. The injection volume was 5.0 g. Components with a purity greater than 95% and less than 0.8% are collected for rotary distillation.

[0052] Among them, the preparation method of phase A is to measure 2 mL of phosphoric acid and pour it into 750 mL of water, adjust the pH to 8.0 with triethylamine, add 200 mL of acetonitrile, and dilute to 1 L with water.

Embodiment 3

[0053] Embodiment 3 first step purification fraction concentration

[0054] The collected semaglut first-step purified fractions were mixed and concentrated by rotary evaporation under reduced pressure at a water temperature of 30°C and a vacuum of -0.09Mbar to remove most of the organic solvents before use.

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Abstract

The invention relates to a purification method of semaglutide. The method comprises the following steps that 1) cracking resin prepared through a solid-phase synthesis method and semaglutide crude peptide from which a protecting group is removed are obtained, and the semaglutide crude peptide is dissolved by using a phosphate buffer solution containing an organic solvent; 2) a semaglutide crude peptide solution is filtered by using an organic filter membrane of 0.22 micro meter, and a filtrate is collected for later use; 3) in first-step purification, by taking a reversed-phase filler as a stationary phase, a phosphate buffer solution containing an organic solvent as a phase A and acetonitrile as a phase B, gradient elution is conducted; 4) in second-step purification, by taking a reversed-phase filler as a stationary phase, a dilute acetic acid solution as a phase A and acetonitrile as a phase B, gradient elution is conducted; and 5) freeze drying is conducted on a concentrated sampleto obtain the semaglutide. According to the method, the phosphate buffer solution containing the organic solvent is used for dissolving the crude peptide, and the pH value of the dissolved crude peptide solution is more stable and crude peptide is not prone to separate out, so that the blockage of a chromatographic column and equipment is avoided, and the separation effect is improved.

Description

technical field [0001] The invention relates to the technical field of purification of polypeptide drugs, in particular to a separation and purification method of semaglutide, which belongs to the field of medicinal chemistry. Background technique [0002] Chinese name: semaglutide [0003] English name: Semaglutide [0004] CAS number: 910463-68-2 [0005] Molecular formula: C 187 h 291 N 45 o 59 [0006] Molecular weight: 4113.64 [0007] Its structure is as follows: [0008] [0009] Semaglutide is a new generation of long-acting GLP-1 analogues developed by Novo Nordisk. It is used for the treatment of type II diabetes. In addition to lowering blood sugar, semaglutide also has weight loss and cardiovascular protection. It is the drug with the best hypoglycemic and weight loss effects among GLP-1 drugs. The FDA approved the marketing of the injectable dosage form in 2017, and approved the marketing of the oral dosage form on September 20, 2019. [0010] Sema...

Claims

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Application Information

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IPC IPC(8): C07K14/605C07K1/36C07K1/34C07K1/20C07K1/14
CPCC07K14/605Y02P20/55
Inventor 马亚平付信张凌云戴政清王宇恩周迎春王庆磊
Owner 深圳深创生物药业有限公司
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