A kind of edaravone drug co-crystal and preparation method thereof

Abstract

The invention belongs to the technical field of organic pharmaceutical co-crystals and particularly relates to a novel edaravone pharmaceutical co-crystal and a preparation method thereof. The edaravone pharmaceutical co-crystal takes edaravone as an active ingredient of the medicine and beta-cyclodextrin as a co-crystal formation; a basic structure unit of the edaravone pharmaceutical co-crystal consists of an edaravone molecule, a beta-cyclodextrin molecule and 10.5 water molecules, wherein a carbonyl oxygen atom and an amido nitrogen atom in the edaravone molecule are taken as a hydrogen bonding acceptor and hydroxyl in the beta-cyclodextrin molecule is taken as a hydrogen bonding donor to form two different intermolecular hydrogen bonds, and the antioxygenation of the edaravone is mainly exerted through clearing free radicals and inhibiting lipid peroxidation so as to inhibit the oxidative damage of brain cells, vascular endothelial cells and nerve cells. The co-crystal prepared by the invention keeps the pharmacological activity of the edaravone, and the solubility, the stability and the bioavailability are all remarkably improved. The result of the solubility test shows that the solubility of the pharmaceutical co-crystal is 6 times that of the edaravone.

Description

technical field

[0001] The invention belongs to the technical field of organic drug co-crystals, and in particular relates to a novel edaravone drug co-crystal and a preparation method of the drug co-crystal. Background technique

[0002] Supramolecular chemistry is a science that studies molecular aggregates that are complex and orderly and have specific structures and functions formed by the association between molecules. Supramolecular chemistry has the following notable features: a. The strong binding force that forms supramolecular compounds is the result of the superposition and synergy of weak interaction forces between different molecules, and is a comprehensive expression of various forces; b. It is formed by the self-assembly of different molecules Supramolecular compounds show new functions that are completely different from the original self-assembled molecules. Its core content is molecular recognition and supramolecular self-assembly through the synergy of wea...

Examples

Embodiment 1

[0053] Accurately weigh 39.9 mg of Edaravone and 260.1 mg of β-cyclodextrin, add 6 ml of a mixed solvent of ethanol and water (volume ratio 1:7), heat to 50-80 °C, and react for 0.5 h under stirring. Stirring was stopped, the temperature was lowered naturally, and after cooling down to room temperature, crystals were precipitated after standing still for 12-24 hours, which was the Edaravone / β-cyclodextrin eutectic.

Embodiment 2

[0055] Accurately weigh 39.9 mg of Edaravone and 260.1 mg of β-cyclodextrin, add 10 ml of a mixed solvent of methanol and water (volume ratio 1:1), heat to 50-65 ° C, and react for 0.5 h under stirring. Stirring was stopped, the temperature was lowered naturally, and after cooling down to room temperature, crystals were precipitated after standing still for 12-24 hours, which was the Edaravone / β-cyclodextrin eutectic.

Embodiment 3

[0057] Accurately weigh 39.9 mg of Edaravone and 260.1 mg of β-cyclodextrin, add 8 ml of a mixed solvent of isopropanol and water (volume ratio 1:5), heat to 50-80 °C, and react for 0.5 h under stirring. Stirring was stopped, the temperature was lowered naturally, and after cooling down to room temperature, crystals were precipitated after standing still for 12-24 hours, which was the Edaravone / β-cyclodextrin eutectic.

technical field

[0001] The invention belongs to the technical field of organic drug co-crystals, and in particular relates to a novel edaravone drug co-crystal and a preparation method of the drug co-crystal. Background technique

[0002] Supramolecular chemistry is a science that studies molecular aggregates that are complex and orderly and have specific structures and functions formed by the association between molecules. Supramolecular chemistry has the following notable features: a. The strong binding force that forms supramolecular compounds is the result of the superposition and synergy of weak interaction forces between different molecules, and is a comprehensive expression of various forces; b. It is formed by the self-assembly of different molecules Supramolecular compounds show new functions that are completely different from the original self-assembled molecules. Its core content is molecular recognition and supramolecular self-assembly through the synergy of wea...

Examples

Embodiment 1

[0053] Accurately weigh 39.9 mg of Edaravone and 260.1 mg of β-cyclodextrin, add 6 ml of a mixed solvent of ethanol and water (volume ratio 1:7), heat to 50-80 °C, and react for 0.5 h under stirring. Stirring was stopped, the temperature was lowered naturally, and after cooling down to room temperature, crystals were precipitated after standing still for 12-24 hours, which was the Edaravone / β-cyclodextrin eutectic.

Embodiment 2

[0055] Accurately weigh 39.9 mg of Edaravone and 260.1 mg of β-cyclodextrin, add 10 ml of a mixed solvent of methanol and water (volume ratio 1:1), heat to 50-65 ° C, and react for 0.5 h under stirring. Stirring was stopped, the temperature was lowered naturally, and after cooling down to room temperature, crystals were precipitated after standing still for 12-24 hours, which was the Edaravone / β-cyclodextrin eutectic.

Embodiment 3

[0057] Accurately weigh 39.9 mg of Edaravone and 260.1 mg of β-cyclodextrin, add 8 ml of a mixed solvent of isopropanol and water (volume ratio 1:5), heat to 50-80 °C, and react for 0.5 h under stirring. Stirring was stopped, the temperature was lowered naturally, and after cooling down to room temperature, crystals were precipitated after standing still for 12-24 hours, which was the Edaravone / β-cyclodextrin eutectic.

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