Crystal form B of aspirin eugenol ester and preparation method thereof

Abstract

The invention discloses a crystal form B of an aspirin eugenol ester. An X-ray powder diffraction pattern below 25 DEG C has a characteristic peak when the 2theta value is 11.96 + / -0.2 degrees and 28.58+ / -0.2 degrees. The invention further discloses a preparation method of the crystal form B of an aspirin eugenol ester. The crystal form B of an aspirin eugenol ester and the preparation method thereof have the following advantages: the stability of a new crystal form is good, the preparation technology is easy to operate, and the cost is low, so that the crystal form B of an aspirin eugenol ester and the preparation method thereof have an important value for optimizing and developing the medicine in the future.

Description

technical field

[0001] The invention relates to the technical field of medicine, in particular to a crystal form B of aspirin eugenol ester and a preparation method thereof. Background technique

[0002] Aspirin eugenol ester is a new type of medicinal compound produced by esterifying aspirin and eugenol on the basis of the prodrug principle. The aspirin eugenol ester shields the carboxyl group of aspirin and the phenolic hydroxyl group of eugenol, thereby reducing the stimulating effect of aspirin on the gastrointestinal tract, and simultaneously solving the problems of irritation and easy oxidation of eugenol. Toxicology experiments showed that the LD of oral aspirin eugenol in mice 50 10.39 g / kg, which is practically non-toxic, LD 50 The value is 0.02 times that of aspirin and 0.27 times that of eugenol. The compound should have obvious advantages, and release the two original drugs of aspirin and eugenol under the action of enzymes in the body and play a synergistic r...

Examples

preparation example Construction

[0023] The invention discloses a method for preparing crystal form B of aspirin eugenol ester, which is prepared by adding an anti-solvent and hot-melting and cooling.

[0024] Anti-solvent addition method is used to prepare crystal form B, which is obtained by heating and dissolving solid aspirin eugenol ester in absolute ethanol, adding an appropriate amount of distilled water dropwise, and collecting the obtained solid.

[0025] Crystal form B is prepared by hot-melt cooling method, which is obtained by placing aspirin eugenol ester in an appropriate amount of 95% ethanol, heating to 60°C until completely dissolved, naturally cooling to room temperature, and filtering.

Embodiment 1

[0045] Example 1 Preparation of aspirin eugenol ester crystal form B by anti-solvent addition method:

[0046] Weigh 30 g of aspirin eugenol ester, add an appropriate amount of absolute ethanol (150 mL), heat and stir to 60°C, and dissolve it completely. Slowly add 15 mL of distilled water dropwise, cool naturally to room temperature, place at 4°C for 24 hours to precipitate all crystals, filter, and dry at 45°C for 24 hours to obtain 28.85 g of crystals with a yield of 96.18%. After testing, the obtained sample was aspirin eugenol ester crystal form B.

Embodiment 2

[0047] Example 2 Preparation of aspirin eugenol ester crystal form B by hot melting and cooling method:

[0048] Weigh 50 g of aspirin eugenol ester, add an appropriate amount of 95% ethanol (250 mL), heat and stir to 60°C, and completely dissolve. Naturally cooled to room temperature, placed at 6°C for 36 hours to precipitate all the crystals, filtered, and dried at 45°C for 24 hours to obtain 49.03 g of crystals with a yield of 98.06%. After testing, the obtained sample was aspirin eugenol ester crystal form B.

technical field

[0001] The invention relates to the technical field of medicine, in particular to a crystal form B of aspirin eugenol ester and a preparation method thereof. Background technique

[0002] Aspirin eugenol ester is a new type of medicinal compound produced by esterifying aspirin and eugenol on the basis of the prodrug principle. The aspirin eugenol ester shields the carboxyl group of aspirin and the phenolic hydroxyl group of eugenol, thereby reducing the stimulating effect of aspirin on the gastrointestinal tract, and simultaneously solving the problems of irritation and easy oxidation of eugenol. Toxicology experiments showed that the LD of oral aspirin eugenol in mice 50 10.39 g / kg, which is practically non-toxic, LD 50 The value is 0.02 times that of aspirin and 0.27 times that of eugenol. The compound should have obvious advantages, and release the two original drugs of aspirin and eugenol under the action of enzymes in the body and play a synergistic r...

Examples

preparation example Construction

[0023] The invention discloses a method for preparing crystal form B of aspirin eugenol ester, which is prepared by adding an anti-solvent and hot-melting and cooling.

[0024] Anti-solvent addition method is used to prepare crystal form B, which is obtained by heating and dissolving solid aspirin eugenol ester in absolute ethanol, adding an appropriate amount of distilled water dropwise, and collecting the obtained solid.

[0025] Crystal form B is prepared by hot-melt cooling method, which is obtained by placing aspirin eugenol ester in an appropriate amount of 95% ethanol, heating to 60°C until completely dissolved, naturally cooling to room temperature, and filtering.

Embodiment 1

[0045] Example 1 Preparation of aspirin eugenol ester crystal form B by anti-solvent addition method:

[0046] Weigh 30 g of aspirin eugenol ester, add an appropriate amount of absolute ethanol (150 mL), heat and stir to 60°C, and dissolve it completely. Slowly add 15 mL of distilled water dropwise, cool naturally to room temperature, place at 4°C for 24 hours to precipitate all crystals, filter, and dry at 45°C for 24 hours to obtain 28.85 g of crystals with a yield of 96.18%. After testing, the obtained sample was aspirin eugenol ester crystal form B.

Embodiment 2

[0047] Example 2 Preparation of aspirin eugenol ester crystal form B by hot melting and cooling method:

[0048] Weigh 50 g of aspirin eugenol ester, add an appropriate amount of 95% ethanol (250 mL), heat and stir to 60°C, and completely dissolve. Naturally cooled to room temperature, placed at 6°C for 36 hours to precipitate all the crystals, filtered, and dried at 45°C for 24 hours to obtain 49.03 g of crystals with a yield of 98.06%. After testing, the obtained sample was aspirin eugenol ester crystal form B.

Images