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Purification method of ganirelix acetate

A technique of ganirelix and a purification method, which is applied in the field of medicinal chemistry, can solve problems such as inhomogeneous salt formation of refined peptides, toxicity of trifluoroacetic acid, unfavorable purification, etc., and achieve good elution peak shape, improved purification scale, and easy The effect of industrial production

Active Publication Date: 2014-08-20
HYBIO PHARMA
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Problems solved by technology

[0007] Prior art CN102584945A discloses a purification method of ganirelix, the purification mobile phase adopted is 0.1% acetic acid system, linear gradient elution in the range of acetonitrile volume ratio of 10%~50%; due to the adoption of prior art synthesis method In the preparation of Ganyrelix, in the cracking step, Ganyrelix will contain a large amount of trifluoroacetic acid, and because the acidity of trifluoroacetic acid is much greater than that of acetic acid, it has a stronger binding ability with Ganyrelix, so that the Salt forms include acetate and trifluoroacetate. This mixed salt form makes the salt formation of refined peptides uneven, which is not conducive to further purification. Moreover, trifluoroacetic acid is also toxic to the human body and cannot be directly used as raw materials. Pharmaceutical and formulation production
[0008] In order to solve the problem of low yield in the prior art, improve the purification yield of ganirelix acetate, and reduce production costs, further research on the purification method is required

Method used

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  • Purification method of ganirelix acetate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1: the purification of ganirelix acetate

[0030] (1) Purification of ganirelix crude peptide:

[0031] Dissolve 2.0 g of crude ganirelix peptide in 100 ml of purified water and acetonitrile (v:v=3:1), filter, and collect the filtrate for later use.

[0032] Purification chromatography conditions:

[0033] Chromatographic column: 50×250mm, filled with octadecylsilane bonded silica gel as stationary phase filler.

[0034] Flow rate: 80ml / min.

[0035] Monitoring wavelength: 280nm.

[0036]Mobile phase A phase: 20mM sodium perchlorate solution, adjust pH to 1.5 with phosphoric acid.

[0037] Mobile Phase B: Acetonitrile.

[0038] gradient:

[0039] Sample loading: 2.0g (100ml).

[0040] After equilibrating the chromatographic column with 75%A+25%B for 5 minutes, load the sample, run gradient purification, monitor and collect the target peak fractions in three sections: before the peak, at the top of the peak, and after the peak. The pre-peak and post-...

Embodiment 2

[0052] Embodiment 2: the purification of ganirelix acetate

[0053] (1) Purification of ganirelix crude peptide:

[0054] Dissolve 2.0 g of crude ganirelix peptide in 100 ml of purified water and acetonitrile (v:v=3:1), filter, and collect the filtrate for later use.

[0055] Purification chromatography conditions:

[0056] Chromatographic column: 50×250mm, filled with octadecylsilane bonded silica gel as stationary phase filler.

[0057] Flow rate: 80ml / min.

[0058] Monitoring wavelength: 280nm.

[0059] Mobile phase A phase: 50mM sodium perchlorate solution, adjust the pH to 2.0 with phosphoric acid.

[0060] Mobile Phase B: Acetonitrile.

[0061] gradient:

[0062] Sample loading: 2.0g (100ml).

[0063] Equilibrate the chromatographic column with 75%A+25%B for 5 minutes, load the sample, run gradient purification, monitor and collect the target peak fractions in three sections: before the peak, at the top of the peak, and after the peak. The pre-peak and post-pea...

Embodiment 3

[0075] Embodiment 3: the purification of ganirelix acetate

[0076] (1) Purification of ganirelix crude peptide:

[0077] Dissolve 2.0 g of crude ganirelix peptide in 100 ml of purified water and acetonitrile (v:v=3:1), filter, and collect the filtrate for later use.

[0078] Purification chromatography conditions:

[0079] Chromatographic column: 50×250mm, filled with octadecylsilane bonded silica gel as stationary phase filler.

[0080] Flow rate: 80ml / min.

[0081] Monitoring wavelength: 280nm.

[0082] Mobile phase A phase: 100mM sodium perchlorate solution, adjust the pH to 2.5 with phosphoric acid.

[0083] Mobile Phase B: Acetonitrile.

[0084] gradient:

[0085] Sample loading: 2.0g (100ml).

[0086] Equilibrate the chromatographic column with 75%A+25%B for 5 minutes, load the sample, run gradient purification, monitor and collect the target peak fractions in three sections: before the peak, at the top of the peak, and after the peak. The pre-peak and post-pe...

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Abstract

The invention provides a purification method of ganirelix acetate. The purification method comprises the steps of (1) purification of ganirelix crude peptide, wherein octadecylsilane bonded silica is adopted as a fixed phase, perchlorate / phosphoric acid solution with certain concentration is taken as an A phase and acetonitrile is taken as a B phase, the ganirelix crude peptide is purified by a gradient-elution high performance liquid chromatography (HPLC) method; (2) salt conversion and purification, wherein the alkylsilane bonded silica is taken as the fixed phase, glacial acetic acid solution with a certain concentration is taken as the A phase and the acetonitrile is taken as the B phase, salt conversion and purification are carried out by adopting the gradient elution HPLC method, and the solution collected and subjected to freeze-drying to obtain the ganirelix acetate. The invention aims at providing the purification method of the ganirelix acetate with stable and controllable process, high yield, high purity, and wide practical value and application prospect.

Description

technical field [0001] The invention relates to a purification method of polypeptide medicine, in particular to a purification method of ganirelix, belonging to the field of medicinal chemistry. Background technique [0002] Ganirelix, English name Ganirelix, molecular formula C 80 h 113 ClN 18 o 13 , is a synthetic decapeptide compound similar to endogenous gonadotropin-releasing hormone (GnRH) (also known as luteinizing hormone-releasing hormone, LHRH), and is an antagonist of GnRH. The structural formula is as follows: [0003] [0004] This product competitively antagonizes the GnRH stimulation of gonadotropes, thereby altering the pathway and causing rapid and reversible inhibition of gonadotropin (luteinizing hormone LH and follicle-stimulating hormone FSH) secretion. It inhibits the secretion of LH from the pituitary gland more significantly than FSH, thereby reducing the production of sex hormones. By inhibiting the fluctuation of LH induced by GnRH in the mi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/23C07K1/16
Inventor 戴柱刘建马亚平袁建成
Owner HYBIO PHARMA
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