Donepezil and valsartan co-amorphous complex, preparation method and application thereof and composition containing co-amorphous complex

A technology of donepezil and amorphous, which is applied in the fields of drug combination, active ingredient of heterocyclic compounds, organic chemistry, etc. It can solve problems such as no research content, no formation of co-crystal or co-amorphous compound between donepezil and valsartan

CN110041244AActive Publication Date: 2019-07-23INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2019-07-23

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Abstract

The invention discloses a co-amorphous complex formed by donepezil shown in a formula (I) and valsartan shown in a formula (II) through combination by non-covalent bonds, a preparation method and an application of the co-amorphous complex and composition containing the co-amorphous complex, specifically, discloses a co-amorphous complex status form formed by donepezil and valsartan, a preparationmethod of the co-amorphous complex formed by donepezil and valsartan as well as an application of the co-amorphous complex formed by donepezil and valsartan as an active pharmaceutical ingredient in preparing drugs for preventing and / or treating cardiovascular diseases such as cardiac failure, myocardial ischemia, hypertension, vascular disease, angina pectoris, hyperlipidemia, atherosclerosis andthe like, neurodegenerative diseases such as alzheimer disease and complication of the multiple diseases. (I) donepezil molecular structural formula and (II) valsartan molecular structural formula are shown in the description.
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Description

technical field

[0001] The present invention relates to the discovery of a co-amorphous solid state form of donepezil-valsartan in a solid state; relates to the invention of a preparation method for a co-amorphous compound of donepezil and valsartan; relates to the invention of a co-amorphous compound containing donepezil Co-amorphous compound with valsartan or a pharmaceutical composition containing a mixed solid substance of donepezil and co-amorphous compound with valsartan in any non-zero ratio; the present invention also relates to co-amorphous compound of donepezil and valsartan as a medicine Active ingredients are used in the preparation of various cardiovascular diseases such as heart failure, myocardial ischemia, hypertension, vascular disease, angina pectoris, hyperlipidemia, atherosclerosis and neurodegenerative diseases such as Alzheimer's Silent disease and the application of disease drugs complicated by the above-mentioned multiple diseases. Background techniqu...

Examples

Embodiment 1

[0078] Donepezil-valsartan co-amorphous solid substance preparation method 1

[0079] Take an appropriate amount of donepezil and valsartan, the molar ratio of the two is 1:1, completely dissolve the sample in the listed solvent at room temperature, heat to reflux, quickly remove the solvent under vacuum, and dry the sample in vacuum. Powder X-ray diffraction analysis is carried out to the obtained sample, and its diffraction pattern is consistent with figure 1 Consistent, indicating that the obtained sample is a co-amorphous compound of donepezil and valsartan. See Table 2 for specific examples.

[0080] Table 2 Donepezil-valsartan co-amorphous solid substance preparation method 1 specific example

[0081]

[0082]

[0083] Donepezil-valsartan co-amorphous solid substance preparation method 2

[0084] Take an appropriate amount of donepezil and valsartan, the molar ratio of the two is 1:1, completely dissolve the sample in the solvent listed in the following table at...

Embodiment 2

[0093] The preparation method 1 (tablet) of combination pharmaceutical preparation:

[0094] A preparation method of a combination drug tablet, characterized in that the pure product of donepezil and valsartan co-amorphous compound, or the mixed solid substance containing donepezil and valsartan co-amorphous compound in any proportion is used as the raw material of the combination drug Medicine, use several kinds of excipients as the adjuvant components for preparing the combination drug tablet, and make a tablet sample with a drug content of 10-500 mg per tablet according to a certain ratio. Table 5 gives the tablet formula ratio:

[0095] Table 5 The preparation formula of donepezil and valsartan co-amorphous compound combination drug tablet

[0096]

[0097] The method for preparing tablet preparations from the pure substance of donepezil and valsartan co-amorphous compound or the mixed solid substance raw material containing donepezil and valsartan co-amorphous compound...

Embodiment 3

[0109] Dosage 1 (tablet) of the combination drug of donepezil and valsartan co-amorphous compound:

[0110] A pharmaceutical composition developed by using samples of co-amorphous compound of donepezil and valsartan as the active ingredient of the drug, characterized in that the co-amorphous compound of donepezil and valsartan is used as the active ingredient of the drug, and the daily dosage is 300mg , which can be prepared as a 100mg ordinary tablet 3 times a day / each time, or a 300mg tablet 1 time a day / each time.

[0111] Dosage 2 (capsule) of the combination drug of donepezil and valsartan co-amorphous compound:

[0112] The pharmaceutical composition developed by using the co-amorphous compound of donepezil and valsartan as the active ingredient of the drug is prepared and developed, which is characterized in that the co-amorphous compound of donepezil and valsartan is used as the active component of the drug, and the daily dosage is 500mg , which can be prepared as 2 t...