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Preparation method of ganirelix acetate

A technology of ganirelix and acetic acid, applied in the field of drug synthesis, can solve problems such as toxicity, increase in processing procedures, and increase in inspection requirements.

Active Publication Date: 2019-06-14
CHIA TAI TIANQING PHARMA GRP CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CN102993274A discloses that Ganirelix crude peptide is purified through the steps of purification and salt conversion in mobile phases of different concentrations (purification mobile phase: sodium perchlorate solution (adjust pH with phosphoric acid)-acetonitrile, salt conversion mobile phase: acetic acid solution-acetonitrile ) to obtain the highest purity of 99.73%, a single impurity less than 0.1% of the product, this method is not suitable for the use of sodium perchlorate solution in industrialized large-scale production process, the perchlorate system is introduced into the industry for purification will appear Many problems: First, sodium perchlorate itself is unstable, flammable, explosive, and toxic. Secondly, the mobile phase needs phosphoric acid to adjust the pH value, filtration and other operations. After purification, desalination is required to remove sodium ions, phosphate ions, perchloric acid and ions. , increasing the follow-up processing procedures, the inspection requirements for finished products will also increase, so it is not suitable for industrialized large-scale production

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  • Preparation method of ganirelix acetate
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  • Preparation method of ganirelix acetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] The preparation of embodiment 1 ganirelix acetate solution

[0073] Mobile phase A: 2% (V / V) acetic acid in water.

[0074] Mobile phase B: 2% (V / V) acetic acid in acetonitrile.

[0075] Chromatographic column: built-in reverse-phase octadecylsilane bonded silica gel as filler.

[0076] Column equilibration: set the flow rate at 2.0L / min, select mobile phase A: mobile phase B=95:5 (V / V) and equilibrate for 50 minutes. After the equilibration is completed, set aside.

[0077] Add 400mL of purified water and 400mL of glacial acetic acid into the beaker, stir evenly, then add 125g of solid Ganirelix crude peptide (obtained by trifluoroacetic acid cracking of Ganirelix resin, HPLC purity 92.95%), after ultrasonic dissolution, Filter through a 0.45 μm filter membrane, collect the filtrate, and set the flow rate at 200 mL / min to load the sample after the column is equilibrated.

[0078] After loading the sample, set the detection wavelength to 280nm and the flow rate to 2....

Embodiment 2

[0081] The preparation of embodiment 2 ganirelix acetate refined products

[0082] Mobile phase A: 1.5% (V / V) acetic acid in water.

[0083] Mobile phase B: 1.5% (V / V) acetic acid in acetonitrile.

[0084] Chromatographic column: built-in reverse-phase octadecylsilane bonded silica gel as filler.

[0085] Column equilibration: set the flow rate at 2.0L / min, select mobile phase A:mobile phase B=85:15 (V / V) and equilibrate for 50 minutes. After the equilibration is completed, set aside.

[0086] After the column was equilibrated, the flow rate was set at 500 mL / min, and the ganirelix acetate solution prepared in Example 1 was loaded.

[0087] After loading the sample, set the detection wavelength to 280nm, and set the elution program according to the parameters in the table below:

[0088]

[0089]Monitor and collect the eluate of the target peak fraction, transfer the eluate to a rotary evaporator, control the temperature of the water bath at 37.5±2.5°C, and vacuum at -0....

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Abstract

The invention relates to the field of drug synthesis, and relates to a preparation method of ganirelix acetate. The preparation method includes the steps of carrying out salt transformation of a ganirelix crude peptide by a chromatographic method and then purifying to obtain a ganirelix acetate refined peptide. The whole process uses only an acetic acid aqueous solution and acetonitrile acetate solution system as an eluent, the purity of the obtained ganirelix acetate reaches 99.82%, and the maximum single impurity content is only 0.04%, no trifluoroacetic acid residue exists at all, no additional ions can be introduced into the process, and the method is easy to operate and suitable for industrialized production.

Description

technical field [0001] The application relates to the field of drug synthesis, in particular to a preparation method of ganirelix acetate. Background technique [0002] Ganirelix Acetate, a decapeptide compound, is a gonadotropin-releasing hormone (GNRH) antagonist and is used for the treatment of fertility disorders. Its structural formula is as follows: [0003] [0004] The preparation of ganirelix acetate has a small specification of 0.25mg / 0.5ml, and the output does not need to be large. However, a large amount of impurities are likely to be produced during the preparation of ganirelix acetate, especially the isomer impurities with very close structures are difficult to remove , the purification process is difficult, which makes it difficult to control the largest single impurity at a very low level and improve the overall purity. [0005] The preparation method of ganirelix acetate disclosed in the prior art is generally extended and coupled one by one by solid-pha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/23C07K1/16A61K38/09A61P15/08
Inventor 胡瑜徐金玲王华张爱明
Owner CHIA TAI TIANQING PHARMA GRP CO LTD
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