Preparation method for carbetocin

A carbetocin and solution technology, applied in the field of polypeptide drug preparation, can solve problems such as unfavorable large-scale production of carbetocin, poisoning of tetrakistriphenylphosphine palladium catalyst, reduction of product purity and use effect, etc. It is beneficial to industrial production, high product yield and low production cost.

Active Publication Date: 2017-03-08
合肥国肽生物科技有限公司
View PDF5 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Most of the existing carbetocin preparation methods are solid-liquid synthesis methods, and the synthesis cycle is long, the production cost is high, and the product activity is low, which is not conducive to the large-scale production of carbetocin
LiOH, NaHCO were used in the synthesis method of ES2115543 3 and DMAP raw materials, which will lead to many impurities, reducing the purity and use effect of the product
Adopted Cys

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
  • Preparation method for carbetocin
  • Preparation method for carbetocin
  • Preparation method for carbetocin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Swelling of amino resin: Weigh 0.1g of Rink-MBHA-Resin with a substitution degree of 0.38mmol / g, add it to the polypeptide synthesis reactor from the open end, take the DCM reagent and add it to the reactor, so that the resin is completely immersed in the DCM solvent , in full contact with the solvent, swelling for 2h.

[0032] 1. Synthesis of carbetocin precursor peptide Ⅰ-amino resin

[0033] Carbetocin precursor peptide Ⅰ-amino resin is:

[0034] Butyric acid (Cl)-Tyr(Me)-Ile-Gln-Asn-Cys-Pro-Leu-Gly-Rink-AM-Resin

[0035] The protected amino acids used in this example are the protected amino acids corresponding to the 1-8 amino acids from the resin and the 4-chlorobutyric acid at the N-terminal, and the molecular weights are shown in Table 1 below:

[0036] Table 1

[0037]

[0038]

[0039] Some commonly used abbreviations in the present invention have the following meanings:

[0040]

[0041] Activation methods for protected amino acids

[0042] Takin...

Embodiment 2

[0057] Swelling of amino resin: Weigh 2g of Rink-MBHA-Resin with a substitution degree of 0.45mmol / g, add it to the polypeptide synthesis reactor from the open end, take the DCM reagent and add it to the reactor, so that the resin is completely immersed in the DCM solvent , soaked overnight.

[0058] 1. Synthesis of carbetocin precursor peptide Ⅰ-amino resin

[0059] Carbetocin precursor peptide Ⅰ-amino resin is:

[0060] Butyric acid(Cl)-Tyr(Me)-Ile-Gln-Asn-Cys-Pro-Leu-Gly-Rink-AM-Resin

[0061] Activation methods for protected amino acids

[0062] Taking the condensation of Fmoc-Gly-amino resin as an example, weigh 510mg Fmoc-Gly-OH and 255mgHOBt in a centrifuge tube according to the calculated theoretical dosage, add 12ml DMF to dissolve it, and then add 200ul DIC to the solution with a dropper , and mix evenly to obtain an activated protected amino acid solution.

[0063] Resin deprotection and washing method

[0064] After the amino resin solution is drained, add 1 / 3...

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 preparation method for carbetocin. The preparation method comprises the following steps: subjecting swelled, deprotected and washed amino resin to reacting with an activated protected amino acid solution in a constant-temperature vibrator, carrying out successive introduction into protected amino acids corresponding to first-to-eighth amino acids accounting from the resin and into butyric acid at the tail end of N; subjecting prepared carbetocin precursor peptide 1-amino resin to deprotection, carrying out washing, then carrying out drying until the dried carbetocin precursor peptide 1-amino resin is of a granular shape, adding a cutting reagent, and carrying out a cutting reaction and settling; dissolving a carbetocin precursor peptide II in a solvent, removing impurities by adopting a reversed phase highly-efficient liquid chromatography method, and carrying out liquid-phase cyclizing so as to obtain a crude carbetocin peptide III; and subjecting the crude carbetocin peptide III to purifying and freeze-drying so as to obtain a pure carbetocin polypeptide. The preparation method provided by the invention utilizes an Fmoc solid-phase synthetic principle to develop a solid-phase synthetic technology; and through process optimization, the yield of crude carbetocin is up to 90% or above, so the yield of carbetocin is greatly improved.

Description

technical field [0001] The invention belongs to the technical field of polypeptide drug preparation methods, in particular to a preparation method of carbetocin. Background technique [0002] Chinese name: carbetocin [0003] English name: Carbetocin [0004] Structural formula: [0005] [0006] Molecular formula: C 45 h 69 N 11 o 12 S [0007] Peptide traits: white loose powder [0008] Carbetocin Acetate is a synthetic long-acting oxytocin octapeptide analogue with agonist properties, and its clinical and pharmacological properties are similar to those of naturally occurring oxytocin. Carbetocin binds to the oxytocin receptor of uterine smooth muscle, causing rhythmic contraction of the uterus, increasing its frequency and increasing uterine tension on the basis of the original contraction. Oxytocin receptor levels in the uterus are low in the non-pregnant state, increase during pregnancy, and peak at delivery. Carbetocin therefore has no effect on the non-...

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): C07K7/16C07K1/06C07K1/04C07K1/20
CPCC07K7/16
Inventor 陈为光孙良玉张旭光沈永亚
Owner 合肥国肽生物科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap