Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Purification method of lixisenatide

A technology of lixisenatide and purification method, applied in the field of purification of lixisenatide, can solve problems such as restricting industrialization, and achieve the effects of easy operation, improved yield and purity

Inactive Publication Date: 2013-01-16
HYBIO PHARMA
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the separation and purification of lixisenatide has become a technical difficulty in the preparation process of this drug, especially the purification of lixisenatide prepared on a large scale has become one of the bottlenecks restricting its industrialization

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Purification method of lixisenatide
  • Purification method of lixisenatide
  • Purification method of lixisenatide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Dissolve 4.0 g of lixisenatide crude peptide (including 1.08 g of lixisenatide) in 200 ml of purified water, filter, and collect the filtrate for later use.

[0039] Purification chromatography conditions:

[0040] High performance liquid chromatography model: Waters 2545

[0041] Chromatographic column: 50×250mm, with phenylsilane bonded silica gel inside as the stationary phase filler, the particle size of the filler is 10μm.

[0042] Flow rate: 80ml / min.

[0043] Detection wavelength: 280nm.

[0044] Mobile phase A: 10mM D-ammonium tartrate and 30mM ammonium dihydrogen phosphate in 20% methanol / 80% aqueous solution (v / v), adjust pH to 2.0 with phosphoric acid.

[0045] Preparation process of mobile phase A: Weigh 18.4g D-ammonium tartrate and 34.5g ammonium dihydrogen phosphate, dissolve in appropriate amount of purified water, filter through a 0.45μm filter membrane, collect all the filtrate into a 10L serum bottle, add 2L chromatographically pure methanol Purif...

Embodiment 2

[0065] Dissolve 6.0 g of lixisenatide crude peptide (including 1.62 g of lixisenatide) in 300 ml of purified water, filter, and collect the filtrate for later use.

[0066] Purification chromatography conditions:

[0067] High performance liquid chromatography model: Waters 2545

[0068] Chromatographic column: 50×250mm, with phenylsilane bonded silica gel inside as the stationary phase filler, the particle size of the filler is 10μm.

[0069] Flow rate: 80ml / min.

[0070] Detection wavelength: 280nm.

[0071] Mobile phase A: 40mM D-sodium tartrate and 20mM ammonium dihydrogen phosphate in 15% methanol / 85% aqueous solution (v / v), adjust the pH to 3.0 with phosphoric acid.

[0072] Preparation process of mobile phase A: weigh 92.0g sodium D-tartrate and 23.0g ammonium dihydrogen phosphate, dissolve in appropriate amount of purified water and filter through a 0.45μm filter membrane, collect all the filtrate into a 10L serum bottle, add 1.5L chromatographically pure methanol ...

Embodiment 3

[0090] Dissolve 6.0 g of lixisenatide crude peptide (including 1.62 g of lixisenatide) in 300 ml of purified water, filter, and collect the filtrate for later use.

[0091] Purification chromatography conditions:

[0092] High performance liquid chromatography model: Waters 2545

[0093] Chromatographic column: 50×250mm, with phenylsilane bonded silica gel inside as the stationary phase filler, the particle size of the filler is 10μm.

[0094] Flow rate: 80ml / min.

[0095] Detection wavelength: 280nm.

[0096] Mobile phase A: 30mM D-potassium tartrate and 40mM potassium dihydrogen phosphate in 10% methanol / 90% aqueous solution (v / v), adjust the pH to 2.5 with phosphoric acid.

[0097] Preparation process of mobile phase A: Weigh 56.1g D-potassium tartrate and 54.4g potassium dihydrogen phosphate, dissolve in appropriate amount of purified water and filter through a 0.45μm filter membrane, collect all the filtrate into a 10L serum bottle, add 1.0L chromatographically pure me...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
particle diameteraaaaaaaaaa
particle diameteraaaaaaaaaa
wavelengthaaaaaaaaaa
Login to View More

Abstract

The invention relates to a purification method of lixisenatide, which comprises the following steps: step 1, purifying crude peptide of lixisenatide by high performance liquid chromatography, wherein the high performance liquid chromatography adopts phenyl silane bonded silica gel as a stationary phase, adopts a methanol / phosphate buffered solution of D-tartrate as a mobile phase A, and adopts acetonitrile as a mobile phase B for gradient elution; step 2, performing salt conversion purification of the fractions obtained in step 1 by high performance liquid chromatography, wherein the high performance liquid chromatography adopts alkyl silane bonded silica gel as a stationary phase, adopts a glacial acetic acid solution as a mobile phase A, and adopts acetonitrile as a mobile phase B for gradient elution; step 3, collecting the solution, and performing freeze-drying.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a method for purifying lixisenatide. Background technique [0002] Diabetes is a global high incidence, which is mainly divided into type I and type II, the latter accounting for more than 90% of the total number of diabetic patients. [0003] Treatment of patients with type 2 diabetes with the glucagon-like peptide 1 (GLP-1) receptor antagonist lixisenatide combined with basal insulin can significantly improve their glycemic control and increase their postprandial blood glucose (PPG) control. [0004] Lixisenatide is a long-chain polypeptide composed of 43 amino acid residues, and there are amino acids such as Ser, His, and Pro in the peptide sequence that are easily isomerized during the solid-phase chemical synthesis of polypeptides, resulting in crude lixisenatide peptides Contains many isomer impurities. Therefore, the separation and purification of lixisena...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/575C07K1/20C07K1/16
Inventor 覃亮政刘建马亚平袁建成
Owner HYBIO PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com