Hesperetin and isonicotinamide eutectic, and preparation method, composition and application thereof

Abstract

The invention discloses a hesperetin and isonicotinamide eutectic, and a preparation method, a composition and application thereof, and belongs to the technical field of medicines. Specifically, the invention discloses the eutectic formed by hesperetin and isonicotinamide, with the molecular formula of (C16H14O6). (C6H6N2O), the preparation method of the hesperetin and isonicotinamide eutectic, and the application of the hesperetin and isonicotinamide eutectic in the preparation of drugs for resisting tumors, resisting oxidation, resisting inflammation and preventing atherosclerosis diseases and complications.

Description

technical field

[0001] The invention relates to a co-crystal formed by hesperetin and isonicotinamide; a preparation method of the co-crystal of hesperetin and isonicotinamide; the co-crystal of hesperetin and isonicotinamide is used as an active ingredient of a medicine and is used in the preparation of anti-aging drugs. Application in tumor, anti-oxidation, anti-inflammation or drugs for preventing atherosclerotic diseases and complications; belongs to the field of medical technology. Background technique

[0002] Hesperetin (English name: Hesperetin) is a dihydroflavonoid compound widely present in citrus fruits. It is a hydrolyzed product of hesperidin. Its structural formula is shown in a. , the role of preventing atherosclerosis [1-3] .

[0003] Isonicotinamide (English name: Isonicotinamide) is a commonly used co-crystal former for drug co-crystals [4] , the structural formula is shown in b. Isonicotinamide is a co-crystal former, currently there are co-crystals o...

Examples

Embodiment 1

[0060] Hesperetin and isonicotinamide co-crystal preparation method 1

[0061] Take an appropriate amount of hesperetin and isonicotinamide, the molar ratio of the two is 1:1, add the sample into a suitable container by solvent suspension method at room temperature, add an appropriate amount of organic solvent, stir for an appropriate time at room temperature, and mix the obtained mixture The suspension solvent was evaporated to dryness, filtered to dry naturally or filtered to vacuum-dried, and the conditions and parameters were shown in Table 3. Carry out powder X-ray diffraction analysis to it, its diffraction pattern and figure 1 Consistent, indicating that the obtained sample is a co-crystal of hesperetin and isonicotinamide.

[0062] Table 3 Hesperetin and isonicotinamide co-crystal preparation method 1 specific example

[0063]

Embodiment 2

[0065] Dissolution and release characteristics of hesperetin and isonicotinamide cocrystal in vitro

[0066] The solubility characteristics of hesperetin and isonicotinamide co-crystal and hesperetin API in pure water, pH 4.5 and pH 6.8 were investigated. The experiment was carried out with reference to the "Technical Guidelines for Dissolution Test of Ordinary Oral Solid Preparations". Dissolution percentage adopts high performance liquid phase method, and external standard method calculates its dissolution percentage content. Take time as the abscissa, and the dissolution percentage as the ordinate to draw the dissolution curve respectively ( Figure 6 ). The data are shown in Table 4.

[0067] Detection conditions: detection system: Aligent 1200, chromatographic column: Agilent Eclipse XDB-C18 (4.6 × 150mm, 5μm); mobile phase: methanol-water (70:30, v / v); flow rate: 1mL min -1 ; Column temperature: 30°C; Detection wavelength: Hesperetin: 280nm; Injection volume: 10 μl. ...

Embodiment 3

[0072] Stability advantage of hesperetin and isonicotinamide co-crystal

[0073] High temperature test: put the sample of hesperetin and isonicotinamide co-crystal in an open clean watch glass, place it at 60°C for 10 days, and take samples on the 0th day, the 5th day and the 10th day. Powder X-ray diffraction analysis was performed on the samples obtained at the above sampling points, and the results showed that the co-crystal of hesperetin and isonicotinamide was stable under the test of high temperature influencing factors.

[0074] High humidity test: put the sample of hesperetin and isonicotinamide co-crystal in an open clean surface dish, place it at 25°C for 10 days at a relative humidity of 90%±5%, and test it on the 0th day, the 5th day and Samples were taken on day 10. Powder X-ray diffraction analysis was performed on the samples obtained at the above sampling points, and the results showed that the co-crystal of hesperetin and isonicotinamide was stable under high...

technical field

[0001] The invention relates to a co-crystal formed by hesperetin and isonicotinamide; a preparation method of the co-crystal of hesperetin and isonicotinamide; the co-crystal of hesperetin and isonicotinamide is used as an active ingredient of a medicine and is used in the preparation of anti-aging drugs. Application in tumor, anti-oxidation, anti-inflammation or drugs for preventing atherosclerotic diseases and complications; belongs to the field of medical technology. Background technique

[0002] Hesperetin (English name: Hesperetin) is a dihydroflavonoid compound widely present in citrus fruits. It is a hydrolyzed product of hesperidin. Its structural formula is shown in a. , the role of preventing atherosclerosis [1-3] .

[0003] Isonicotinamide (English name: Isonicotinamide) is a commonly used co-crystal former for drug co-crystals [4] , the structural formula is shown in b. Isonicotinamide is a co-crystal former, currently there are co-crystals o...

Examples

Embodiment 1

[0060] Hesperetin and isonicotinamide co-crystal preparation method 1

[0061] Take an appropriate amount of hesperetin and isonicotinamide, the molar ratio of the two is 1:1, add the sample into a suitable container by solvent suspension method at room temperature, add an appropriate amount of organic solvent, stir for an appropriate time at room temperature, and mix the obtained mixture The suspension solvent was evaporated to dryness, filtered to dry naturally or filtered to vacuum-dried, and the conditions and parameters were shown in Table 3. Carry out powder X-ray diffraction analysis to it, its diffraction pattern and figure 1 Consistent, indicating that the obtained sample is a co-crystal of hesperetin and isonicotinamide.

[0062] Table 3 Hesperetin and isonicotinamide co-crystal preparation method 1 specific example

[0063]

Embodiment 2

[0065] Dissolution and release characteristics of hesperetin and isonicotinamide cocrystal in vitro

[0066] The solubility characteristics of hesperetin and isonicotinamide co-crystal and hesperetin API in pure water, pH 4.5 and pH 6.8 were investigated. The experiment was carried out with reference to the "Technical Guidelines for Dissolution Test of Ordinary Oral Solid Preparations". Dissolution percentage adopts high performance liquid phase method, and external standard method calculates its dissolution percentage content. Take time as the abscissa, and the dissolution percentage as the ordinate to draw the dissolution curve respectively ( Figure 6 ). The data are shown in Table 4.

[0067] Detection conditions: detection system: Aligent 1200, chromatographic column: Agilent Eclipse XDB-C18 (4.6 × 150mm, 5μm); mobile phase: methanol-water (70:30, v / v); flow rate: 1mL min -1 ; Column temperature: 30°C; Detection wavelength: Hesperetin: 280nm; Injection volume: 10 μl. ...

Embodiment 3

[0072] Stability advantage of hesperetin and isonicotinamide co-crystal

[0073] High temperature test: put the sample of hesperetin and isonicotinamide co-crystal in an open clean watch glass, place it at 60°C for 10 days, and take samples on the 0th day, the 5th day and the 10th day. Powder X-ray diffraction analysis was performed on the samples obtained at the above sampling points, and the results showed that the co-crystal of hesperetin and isonicotinamide was stable under the test of high temperature influencing factors.

[0074] High humidity test: put the sample of hesperetin and isonicotinamide co-crystal in an open clean surface dish, place it at 25°C for 10 days at a relative humidity of 90%±5%, and test it on the 0th day, the 5th day and Samples were taken on day 10. Powder X-ray diffraction analysis was performed on the samples obtained at the above sampling points, and the results showed that the co-crystal of hesperetin and isonicotinamide was stable under high...

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