Huperzine A polymorphism body, preparation method thereof, pharmaceutical composition comprising polymorphism body and application thereof

Abstract

The invention discloses a huperzine A polymorphism body, a preparation method thereof, a pharmaceutical composition comprising the polymorphism body and an application thereof. Partial of the huperzine A polymorphism body has better solubility than that of a commercially available medicinal crystal form and is more beneficial to absorption of medicine. Partial of the huperzine A polymorphism body has much lower hygroscopicity than that of the commercially available medicinal crystal form and is more beneficial to preparation and storage of medicine preparations.

Description

technical field

[0001] The present invention is a divisional application of the patent application for invention with the application number 2012100784749 submitted by the applicant Shanghai Institute of Materia Medica, Chinese Academy of Sciences on March 22, 2012.

[0002] The invention belongs to the field of medicinal chemistry polymorph research, and specifically relates to the preparation of huperzine A polymorph by different crystallization methods and the research on its synthesis process. Background technique

[0003] Polymorphism refers to the phenomenon that solid substances form solid states with different physical and chemical properties in two or more different spatial arrangements. In the field of pharmaceutical research, polymorphism also includes multi-component crystal forms such as organic solvates and hydrates. Drug polymorphism widely exists in the drug development process and is an inherent characteristic of small organic molecules. Theoretically, sma...

Examples

Embodiment 1

[0056] Example 1: Preparation of huperzine A crystal form I.

[0057] Mix 50 mg of huperzine A raw material (amorphous) with 1 ml of acetone, heat to 50° C. and keep stirring at 50° C. for 3 days, and filter to obtain a white solid. After evaporating the solvent at room temperature, the white solid was dried under reduced pressure with an oil pump for 12 hours to obtain a crystalline powder, which was determined by X-ray powder diffraction, showing that the obtained crystal form was Form I. The specific peak positions are shown in Table 1 below.

[0058] Table 1: X-ray powder diffraction data of Huperzine A crystal form I in Example 1 of the present invention

[0059]

[0060] Other tests were carried out on the obtained sample, and the obtained DSC thermal spectrum, infrared spectrum and Raman spectrum were as follows: Figure 1b , 1c , 1d shown.

Embodiment 2

[0061] Example 2: Preparation of huperzine A crystal form II.

[0062] Put 25 mg of huperzine A crystal form I in an oven at 125 degrees Celsius and heat for 2 hours to obtain a crystalline powder, which was determined by X-ray powder diffraction to show that the obtained crystal form was crystal form II. The specific peak positions are shown in Table 2 below.

[0063] Table 2: X-ray powder diffraction data of Huperzine A crystal form II in Example 2 of the present invention

[0064]

[0065]

[0066] Other tests were carried out on the obtained sample, and the obtained DSC thermal spectrum, infrared spectrum and Raman spectrum were as follows: Figure 2b , 2c , as shown in 2d.

Embodiment 3

[0067] Example 3: Preparation of huperzine A crystal form III.

[0068] Mix 50 mg of huperzine A crystalline form I with 1 ml of acetonitrile, heat to 50° C. and keep stirring at 50° C. for 2 days, and filter to obtain a white solid. After evaporating the solvent at room temperature, the white solid was placed in a vacuum drying oven at 100°C, and dried for 24 hours under vacuum with an oil pump to obtain a crystalline powder, which was determined by X-ray powder diffraction, showing that the obtained crystal form was crystal Type III. The specific peak positions are shown in Table 3 below.

[0069] Table 3: X-ray powder diffraction data of Huperzine A crystal form III in Example 3 of the present invention

[0070]

[0071] Other tests were carried out on the obtained sample, and the obtained DSC thermal spectrum, infrared spectrum and Raman spectrum were as follows: Figure 3b , 3c , 3d shown.

technical field

[0001] The present invention is a divisional application of the patent application for invention with the application number 2012100784749 submitted by the applicant Shanghai Institute of Materia Medica, Chinese Academy of Sciences on March 22, 2012.

[0002] The invention belongs to the field of medicinal chemistry polymorph research, and specifically relates to the preparation of huperzine A polymorph by different crystallization methods and the research on its synthesis process. Background technique

[0003] Polymorphism refers to the phenomenon that solid substances form solid states with different physical and chemical properties in two or more different spatial arrangements. In the field of pharmaceutical research, polymorphism also includes multi-component crystal forms such as organic solvates and hydrates. Drug polymorphism widely exists in the drug development process and is an inherent characteristic of small organic molecules. Theoretically, sma...

Examples

Embodiment 1

[0056] Example 1: Preparation of huperzine A crystal form I.

[0057] Mix 50 mg of huperzine A raw material (amorphous) with 1 ml of acetone, heat to 50° C. and keep stirring at 50° C. for 3 days, and filter to obtain a white solid. After evaporating the solvent at room temperature, the white solid was dried under reduced pressure with an oil pump for 12 hours to obtain a crystalline powder, which was determined by X-ray powder diffraction, showing that the obtained crystal form was Form I. The specific peak positions are shown in Table 1 below.

[0058] Table 1: X-ray powder diffraction data of Huperzine A crystal form I in Example 1 of the present invention

[0059]

[0060] Other tests were carried out on the obtained sample, and the obtained DSC thermal spectrum, infrared spectrum and Raman spectrum were as follows: Figure 1b , 1c , 1d shown.

Embodiment 2

[0061] Example 2: Preparation of huperzine A crystal form II.

[0062] Put 25 mg of huperzine A crystal form I in an oven at 125 degrees Celsius and heat for 2 hours to obtain a crystalline powder, which was determined by X-ray powder diffraction to show that the obtained crystal form was crystal form II. The specific peak positions are shown in Table 2 below.

[0063] Table 2: X-ray powder diffraction data of Huperzine A crystal form II in Example 2 of the present invention

[0064]

[0065]

[0066] Other tests were carried out on the obtained sample, and the obtained DSC thermal spectrum, infrared spectrum and Raman spectrum were as follows: Figure 2b , 2c , as shown in 2d.

Embodiment 3

[0067] Example 3: Preparation of huperzine A crystal form III.

[0068] Mix 50 mg of huperzine A crystalline form I with 1 ml of acetonitrile, heat to 50° C. and keep stirring at 50° C. for 2 days, and filter to obtain a white solid. After evaporating the solvent at room temperature, the white solid was placed in a vacuum drying oven at 100°C, and dried for 24 hours under vacuum with an oil pump to obtain a crystalline powder, which was determined by X-ray powder diffraction, showing that the obtained crystal form was crystal Type III. The specific peak positions are shown in Table 3 below.

[0069] Table 3: X-ray powder diffraction data of Huperzine A crystal form III in Example 3 of the present invention

[0070]

[0071] Other tests were carried out on the obtained sample, and the obtained DSC thermal spectrum, infrared spectrum and Raman spectrum were as follows: Figure 3b , 3c , 3d shown.

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