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Preparation method for oxytocin deamidation impurity

A technology for deamidation and impurities, applied in the field of biopharmaceuticals, can solve the problems of dilute sample concentration, low yield, complicated preparation process, etc., and achieve the effect of optimizing the production process

Active Publication Date: 2017-05-31
SPH NO 1 BIOCHEM & PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The technical problem to be solved by the present invention is to provide a oxytocin deamidation impurity preparation in order to overcome the defects of complex preparation process, low yield, dilute sample concentration and bulky volume in the prior art. Preparation

Method used

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  • Preparation method for oxytocin deamidation impurity
  • Preparation method for oxytocin deamidation impurity
  • Preparation method for oxytocin deamidation impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1 (HPLC method detects oxytocin deamidation impurity precursor crude product and purification intermediate solution purity and quantification)

[0033] Instrument: Agilent 1200 HPLC

[0034] Separation column: Waters XBridge-C18, 4.6×150mm, 5μm

[0035] Mobile phase: A is 50% by volume acetonitrile aqueous solution, B is 0.02M KH 2 PO 4 pH 3.0 aqueous solution, flow rate is 1.0mL / min, detection wavelength is 220nm, detected at room temperature, elution gradient is shown in the table below, percentages are volume percentages.

[0036] Elution step Elution time eluent 1 0~15min 35%A+65%B 2 15~25min 35%A+65%B→100%A 3 25~28min 100％A 4 28.0~28.1min 100%A→35%A+65%B 5 28.1~32min 35%A+65%B

Embodiment 2

[0037] Embodiment 2 (50mm inner diameter L&L4002 preparative column packing)

[0038] Using Load&Lock dynamic axial compression and static locking technology, the filler is silica gel C18 (Kromasil C18), with a pore size of 10nm, a particle size of 10μm, a column packing density of 0.66g / mL, and a column bed pressure of 133bar, using a Varian chromatography packing system, 325g Dry powder filler, 650mL of isopropanol is stirred and homogenized, poured into L&L4002 preparative column with an inner diameter of 50mm, the compression ratio is 1.5:1, and the carrier gas is N 2 , adjust the carrier gas pressure so that the pressure of the oil pressure gauge is 200bar, and the dynamic axial compression to the height of the column bed is 25.5cm, which is used as the preparative column for the reverse-phase cyclization, reverse-phase purification and reverse-phase desalination schemes.

Embodiment 3

[0039] Example 3 Reverse-phase cyclization, reverse-phase purification and reverse-phase desalting of oxytocin deamidation impurity precursor crude material

[0040] Instrument: Varian SD-1 high pressure liquid phase preparation system

[0041] Chromatographic column: Example 2 self-packed preparative column Load&Lock4002 50×255mm, C18 10μm10nm

[0042] The crude product of oxytocin deamidation impurity precursor is the crude product of oxytocin deamidation impurity precursor obtained through cracking and drying by solid-phase synthesis method, and its structural formula is Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly of trifluoroacetate.

[0043]The crude oxytocin deamidation impurity precursor solution is a 5 g / L solution formed by dissolving the crude oxytocin deamidation impurity precursor in 5% acetonitrile aqueous solution.

[0044] Mobile phase A1 is purified water, A2 is 0.02 volume percent H 2 o 2 pH is 7.5 NaOH aqueous solution, mobile phase B is acetonitrile, and mobile ...

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Abstract

The invention discloses a preparation method for an oxytocin deamidation impurity. The preparation method comprises the following step of: successively subjecting a solution of a crude oxytocin deamidation impurity precursor to reversed-phase cyclization, reversed-phase purification and reversed-phase desalination by adopting high-performance liquid-phase reversed-phase chromatography, wherein a filling material for the high-performance liquid-phase reversed-phase chromatography is silica gel C18; and the crude oxytocin deamidation impurity precursor contains two free sulfhydryl groups. The preparation method provided by the invention innovatively adopts a reversed-phase adsorption method for cyclization, purification and desalination, solves the problems of cyclization, purification and desalination once for all, optimizes the production process, and is applicable to continuous industrial production.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals. More specifically, the present invention relates to a preparation method of oxytocin deamidation impurity. Background technique [0002] Oxytocin, also known as oxytocin, English name is Oxytocin, structural formula: [0003] [0004] The molecular formula is: C 43 h 66 N 12 o 12 S 2 , the molecular weight is 1007.2 [0005] Oxytocin is used to induce labor, oxytocin, postpartum and post-abortion uterine bleeding caused by uterine atony or poor abdominal contraction; understand placental reserve function (oxytocin provocation test); nasal drops can promote milk discharge. Oxytocin can indirectly stimulate the contraction of uterine smooth muscle, simulating the uterine contraction of normal childbirth, leading to cervical dilatation, and the uterine response to oxytocin gradually increases during pregnancy and reaches its peak at full term. Oxytocin can also stimulate the contraction ...

Claims

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Application Information

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IPC IPC(8): C07K7/16C07K1/20C07K1/02
Inventor 江锡铭丁金国黄臻辉
Owner SPH NO 1 BIOCHEM & PHARMA CO LTD
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