Novel method for producing peramivir trihydrate, and water-based drying thereof

A technology of peramivir trihydrate and carboxylic acid trihydrate, which is applied in the field of neuraminidase infection inhibitors and can solve the problems of difficulty in maintaining moisture value, natural drying method unsuitable for industrialized mass production, and GMP standards. , to achieve the effect of stable preparation

Active Publication Date: 2022-02-11
CHONGKUNDANG BIO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since peramivir trihydrate is a drug prepared as an injection, in natural drying, there are different drying conditions according to the internal humidity, and it is difficult to maintain a uniform moisture value, so the natural drying method is not suitable for industrialized mass production and GMP standard
[0020] Moreover, the KR1020107005427 / CN2008001459 / WO2009021404 and KR1020127025551 / CN2008001459 / WO2009021404 patents shown in Figure 2 of the preparation process also use methanol solvent to prepare trihydrate, and the drying process is also used to prepare peramivir trihydrate through a process that is not suitable for GMP regulations and industrial production. Hydrate

Method used

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  • Novel method for producing peramivir trihydrate, and water-based drying thereof
  • Novel method for producing peramivir trihydrate, and water-based drying thereof
  • Novel method for producing peramivir trihydrate, and water-based drying thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Example 1: Peramivir trihydrate ((1S, 2S, 3R, 4R)-3-[(S)-1-acetylamino-2-ethylbutyl]-4-guanidino-2-hydroxy Preparation of cyclopentane-1-carboxylic acid trihydrate) (1)

[0084]

[0085] Add 30.0kg of (1S, 2S, 3R, 4R)-3-[(S)-1-acetamido-2-ethylbutyl]-4-guanidino-2-hydroxyl ring in a 500.0L capacity reactor Pentane-1-carboxylic acid (Peramivir; Peramivir), and suspended in 240.0 L of purified water. The reactant was heated to about 95° C. to completely dissolve the suspension, stirred, and allowed to cool naturally. When the temperature of the reactant was 85°C, 45.0 L of 1-propanol (1-Propanol) was slowly added, and naturally cooled to 25°C while stirring. At this time, crystallites of peramivir trihydrate were produced at a temperature of about 40°C. When the temperature of the reactor reached 25° C. by natural cooling, it was stirred for about 12 hours to cause a phase transition of Form A. Then, the temperature of the reactor was cooled to 5° C., and stirred f...

Embodiment 2

[0087] Example 2: Peramivir trihydrate ((1S, 2S, 3R, 4R)-3-[(S)-1-acetylamino-2-ethylbutyl]-4-guanidino-2-hydroxy Preparation of cyclopentane-1-carboxylic acid trihydrate) (2)

[0088]

[0089] Add 30.0kg of (1S, 2S, 3R, 4R)-3-[(S)-1-acetamido-2-ethylbutyl]-4-guanidino-2-hydroxyl ring in a 500.0L capacity reactor Pentane-1-carboxylic acid (Peramivir; Peramivir), and suspended in 240.0 L of purified water. The reactant was heated to about 95° C. to completely dissolve the suspension, stirred, and allowed to cool naturally. When the temperature of the reactant was 85°C, 45.0L of 2-propanol (2-Propanol) was slowly added, and naturally cooled to 25°C while stirring. At this time, crystallites of peramivir trihydrate were produced at a temperature of about 40°C. When the temperature of the reactor reached 25° C. by natural cooling, it was stirred for about 12 hours to cause a phase transition of Form A. Then, the temperature of the reactor was cooled to 5° C., and stirred fo...

Embodiment 3

[0100] Example 3: Peramivir trihydrate ((1S, 2S, 3R, 4R)-3-[(S)-1-acetylamino-2-ethylbutyl]-4-guanidino-2-hydroxy Preparation of cyclopentane-1-carboxylic acid trihydrate) (3)

[0101]

[0102] Add 30.0kg of (1S, 2S, 3R, 4R)-3-[(S)-1-acetamido-2-ethylbutyl]-4-guanidino-2-hydroxyl ring in a 500.0L capacity reactor Pentane-1-carboxylic acid (Peramivir; Peramivir), and suspended in 240.0 L of purified water. The reactant was heated to about 95° C. to completely dissolve the suspension, stirred, and allowed to cool naturally. When the temperature of the reactant was 85°C, 45.0 L of 1-pentanol (1-Pentanol) was slowly added, and naturally cooled to 25°C while stirring. At this time, crystallites of peramivir trihydrate were produced at a temperature of about 40°C. When the temperature of the reactor reached 25° C. by natural cooling, it was stirred for about 12 hours to cause a phase transition of Form A. And, the temperature of the reactor was cooled to 5° C., further stirre...

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PUM

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Abstract

The present invention relates to a method for producing peramivir trihydrate, which is an inhibitor of neuraminidase infection, as an anti-influenza agent. According to the production method of the present invention, peramivir trihydrate can be produced with high yield and stability through a process suitable for producing excellent pharmaceuticals and quality control standards (GMP) without using highly-toxic methanol and activated carbon.

Description

technical field [0001] This application claims priority from Korean Patent Application No. 10-2019-0080188 filed with the Korean Patent Office on July 3, 2019, the disclosure of which is incorporated herein by reference. [0002] The invention relates to a preparation method of peramivir trihydrate, a neuraminidase infection inhibitor used as an anti-influenza preparation. Background technique [0003] Influenza virus (Influenza virus) is a contagious viral disease that causes acute respiratory disease, and is a virus commonly known as influenza. In 1931, Shope isolated influenza virus from pigs for the first time, and Smith, Andrews and Laidlow isolated influenza virus from humans in 1933. Currently, influenza viruses cause various acute respiratory diseases in humans worldwide through multiple mutations and are therefore managed as a virus with increased morbidity and mortality. Recently, when influenza virus emerges as a new virus through various mutations, a large incr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C277/08C07C279/16
CPCC07C277/08C07C2601/08C07C279/16C07B2200/07
Inventor 金熙云金仁圭李明锡姜兴模金世振崔仁硕
Owner CHONGKUNDANG BIO
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