A kind of preparation method of liraglutide
A technology of liraglutide and liraglutide, which is applied in the field of preparation of liraglutide, can solve the problems of low amino acid access rate and reduced yield, and achieve the reduction of purification difficulty, production cost and preparation cost low effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0044] Preparation of Liraglutide Peptide Backbone Resin:
[0045] Using Fmoc-Gly-Wang resin as the initial carrier, through the deprotection of Fmoc and coupling reaction, the amino acids are sequentially coupled and protected to prepare the main chain resin of liraglutide peptide. Gly is used as the first coupled amino acid, and His is used as the first coupling amino acid. The 31 coupled amino acids are sorted, and the coupled amino acid fragments are:
[0046]Boc-His(trt)-Ala-Glu(otbu)-Gly-Thr(tbu)-Phe-Thr(tbu)-Ser(tbu)-Asp(otbu)-Y(tbu)-Tyr(tbu)-Leu- Glu(otbu)-Gly-Gln(trt)-X(alloc)-Glu(otbu)-Phe-Ile-Ala-Trp(boc)-Leu-Val-Arg(pbf)-Gly-Arg(pbf)-Gly -Wang Resin,
[0047] Where X is Ala-Ala-Lys, Y is Val-Ser-Ser;
[0048] When X is inserted, the corresponding protected amino acid is Fmoc-Ala-Ala-Lys(alloc)-OH;
[0049] When Y is inserted, the corresponding protected amino acid is Fmoc-Val-Ser(tbu)-Ser(tbu)-OH;
[0050] When His is inserted, the corresponding protected amin...
Embodiment 2
[0078] On the basis of Example 1, the crude product of liraglutide was prepared:
[0079] Take liraglutide peptide resin, add lysate with a volume ratio of TFA:EDT:TIS:water=90:4:2:4, the amount of lysate is 5mL / g resin, and stir evenly. Stir the reaction at room temperature for 3 hours, filter the reaction mixture with a sand core funnel, collect the filtrate, wash the resin with a small amount of TFA 3 times, combine the filtrate and concentrate under reduced pressure, add anhydrous ether to precipitate, then wash the precipitate 3 times with anhydrous ether, pump The dried off-white powder is crude liraglutide.
Embodiment 3
[0081] On the basis of Example 2, the purification process of crude liraglutide:
[0082] The crude liraglutide was dissolved in 20% acetonitrile aqueous solution with ammonia water to adjust the pH value to 10, filtered through a 0.45 μm mixed microporous membrane, and purified for later use;
[0083] High performance liquid chromatography is used for purification. The purified chromatographic column is octadecyl bonded silica gel with a diameter of 10cm and a filler of 10um. The mobile phase is dilute ammonia solution and acetonitrile solution respectively, the flow rate is 120ml / min, the sample loading is 5-10g, and the detection wavelength of the chromatograph is 230nm.
[0084] After multiple purifications, the qualified main peak was collected, analyzed in liquid phase to detect its purity, and concentrated under reduced pressure to obtain a dilute ammonia solution of liraglutide, which was freeze-dried to obtain 18.8 g of liraglutide, with a total yield of 10.1%.
[0...
PUM
Property | Measurement | Unit |
---|---|---|
degree of substitution | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
- R&D Engineer
- R&D Manager
- IP Professional
- Industry Leading Data Capabilities
- Powerful AI technology
- Patent DNA Extraction
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