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

Synthesis method of bivalirudin

A technology of bivalirudin and a synthesis method, applied in the field of polypeptide drug preparation, can solve the problems of low expression efficiency, application limitation, difficulty in product extraction and recovery, etc., and achieve the effects of improving utilization rate, increasing yield, and reducing the generation of impurities

Active Publication Date: 2021-12-28
浙江湃肽生物股份有限公司南京分公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In general, recombinant DNA technology, due to the need for a long-term, expensive research and development stage, and the problems of low expression efficiency and difficult product extraction and recovery in the fermentation stage
Its application is very limited

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
  • Synthesis method of bivalirudin
  • Synthesis method of bivalirudin
  • Synthesis method of bivalirudin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Synthesis of Bivalirudin

[0047] 1. Activation of resin

[0048] Take 45g of Wang resin and add 690g of activation solution, 100r / min oscillating reaction for 2h; after the reaction, filter out the resin, wash and dry to obtain the activated resin; the activation solution includes 600g of methylene chloride, 60g of B-butyrolactone, Nadic anhydride 30g.

[0049] 2. Synthesis of Leu-resin

[0050] Take 50g of swelled activated resin and 0.08mol Fmoc-Leu, add 0.08mol DMF to swell, then ice-bath, continue to add 0.08mol DCC, 0.08mol HOBt and 0.0025mol DMAP, after 2h in ice-bath, 4°C, 100r / min stirring overnight; After stirring, filter, wash and dry to obtain Fmoc-Leu-resin; add 100g of pyridine / dichloromethane / DMF mixed solution (V / V / V=1:1:3) to Fmoc-Leu-resin, react for 30min, suction filter and Wash and dry to obtain Leu-resin.

[0051] 3. Synthesis of bivalirudin-resin

[0052] According to the operation method in step 2, amino acids were sequentially coupled to pr...

Embodiment 2

[0062] Synthesis of Bivalirudin

[0063] 1. Activation of resin

[0064] Take 30g of Wang resin and add 573g of activation solution, oscillate at 100r / min for 1h; filter out the resin after the reaction, wash and dry to obtain the activated resin; the activation solution is 540g of dichloromethane, 30g of B-butyrolactone, Nadic anhydride 3g.

[0065] 2. Synthesis of Leu-resin

[0066] Take 30g of swelled activated resin and 0.05mol Fmoc-Leu, add 0.05mol DMF to swell, then ice-bath, continue to add 0.05mol DCC, 0.05mol HOBt and 0.001mol DMAP, after 1h in ice-bath, stir overnight at 2°C at 100r / min; After stirring, filter, wash and dry to obtain Fmoc-Leu-resin; add 90g of pyridine / dichloromethane / DMF mixed solution (V / V / V=0.25:1:1) to Fmoc-Leu-resin, react for 20min, suction filter and Wash and dry to obtain Leu-resin.

[0067] 3. Synthesis of bivalirudin-resin

[0068] With embodiment 1.

[0069] 4. Deprotection

[0070] Take 100g of 90% TFA solution, 10g of (S)-glycidol...

Embodiment 3

[0074] Synthesis of Bivalirudin

[0075] 1. Activation of resin

[0076] Take 60g of Wang resin and add 915g of activation solution, oscillate at 120r / min for 4h; filter out the resin after the reaction, wash and dry to obtain the activated resin; the activation solution is 780g of methylene chloride, 90g of B-butyrolactone, Nadic anhydride 45g.

[0077] 2. Synthesis of Leu-resin

[0078] Take 60g of swollen activated resin and 0.15mol Fmoc-Leu, add 0.15mol DMF to swell, then ice-bath, continue to add 0.15mol DCC, 0.15mol HOBt and 0.005mol DMAP, after 5h in ice-bath, stir overnight at 4°C at 120r / min; After stirring, filter, wash and dry to obtain Fmoc-Leu-resin; add 120g of dichloromethane / DMF mixed solution (V / V / V=1:1:3) to Fmoc-Leu-resin and react for 50min, then suction filter and wash and dry Dry to obtain Leu-resin. (modified according to the content of the invention)

[0079] 3. Synthesis of bivalirudin-resin

[0080] With embodiment 1.

[0081] 4. Deprotection ...

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

No PUM Login to View More

Abstract

The invention discloses a synthesis method of bivalirudin, and belongs to the technical field of polypeptide drug preparation. The synthesis method of the bivalirudin comprises the following steps: step (1), resin activation: activating resin with an activating solution to obtain activated resin, wherein the activating solution comprising dichloromethane, B-butyrolactone and nadic anhydride; step (2), synthesis of Leu-resin: synthesizing the swelled activated resin and Fmoc-Leu into the Leu-resin by adopting a solid-phase synthesis method; (3) synthesis of bivalirudin-resin: synthesizing the bivalirudin-resin by adopting a solid-phase synthesis method; and (4) deprotection: performing deprotection on the bivalirudin-resin to obtain the bivalirudin. The yield of the bivalirudin synthesized by the synthesis method is higher.

Description

technical field [0001] The invention relates to the technical field of preparation of polypeptide drugs, in particular to a synthesis method of bivalirudin. Background technique [0002] Biologically active peptides have unique advantages as drugs: first, small molecular weight, non-immunogenicity, and relatively safe; second, relatively simple structure, clear functions, specificity, and small side effects; third, small molecules, easy synthesis, and easy structure Transformation, low production cost; Fourth, peptide drugs are easy to absorb from multiple channels, so the route of administration can be diversified (such as: oral, spray, transdermal absorption, etc.); Fifth, the synthetic peptide has high purity and no heat source question. Because of this, special attention has been paid to the research on peptide drugs at home and abroad. [0003] Bivalirudin is a hirudin-based, synthetic anticoagulant drug. It is a polypeptide chain composed of 20 amino acids, and the m...

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
IPC IPC(8): C07K14/815C07K1/04C07K1/06
CPCC07K14/815
Inventor 刘志国魏祝宇潘海良叶有志汪岳斌
Owner 浙江湃肽生物股份有限公司南京分公司
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