Methylpyrazine derivative-piperazine eutectic crystal

A technology for methylpyrazine and derivatives, applied in the field of methylpyrazine derivatives-piperazine co-crystals, can solve the problems of low yield, unmentioned characterization parameters, etc., and achieves high bioavailability and solid state. Good stability and high stability

Active Publication Date: 2020-08-11
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there are many related reports about acipimox, but mainly about its preparation, preparation, physical and chemical properties and pharmacological properties. There are few reports about its crystal eutectic structure. Patents US2005239803A1, CN 10350896 3A, etc. The preparation method of acipimox was disclosed, and the patent CN86103304-2 obtained the acipimox precipitate in crystal form, which was acipimox hydrate, and the yield was low
In the previous reports, there were few reports on the acipimus cocrystal cocrystal, and the crystallographic characterization parameters of the acipimus cocrystal were not mentioned

Method used

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  • Methylpyrazine derivative-piperazine eutectic crystal
  • Methylpyrazine derivative-piperazine eutectic crystal
  • Methylpyrazine derivative-piperazine eutectic crystal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Add 68.9mg of acipimox and 38.5mg of piperazine into 8ml of methanol, heat to 60°C and stir to dissolve, reflux reaction for 10 hours, slowly cool down to 15-20°C, stand for crystallization under temperature control for 26 hours, filter , Vacuum-dried at 50°C for 8h, the acipimus-piperazine co-crystal, the yield was 95.88%, the purity was 99.94%, and the impurity I: 0.04%.

Embodiment 2

[0057] Add 65.5mg of acipimox and 38.5mg of piperazine into 5.5ml of ethanol, heat to 70°C and stir to dissolve, reflux for 11 hours, slowly lower the temperature to 20-25°C, stand for crystallization under temperature control for 28 hours, filter , vacuum-dried at 45°C for 8h, the yield of acipimus-piperazine cocrystal was 95.68%, the purity was 99.92%, and the impurity I: 0.05%.

Embodiment 3

[0059] Add 72.3mg of acipimox and 38.5mg of piperazine to 13ml of acetone, heat to 55°C and stir to dissolve, reflux reaction for 12 hours, slowly cool down to 10-15°C, stand for crystallization under temperature control for 30 hours, filter , Vacuum-dried at 50°C for 8h, acipimus-piperazine cocrystal, yield 94.81%, purity 99.90%, impurity I: 0.07%.

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Abstract

The invention belongs to the technical field of medicines, and particularly provides a methylpyrazine derivative-piperazine eutectic crystal, a preparation method thereof and application of the eutectic crystal in preparation of hypolipidemic drugs. The methylpyrazine derivative-piperazine eutectic crystal is radiated by Cu-Kalpha, and an X-ray diffraction pattern expressed by 2theta has characteristic peaks at 8.8 + / -0.2 degrees, 13.0 + / -0.2 degrees, 14.7 + / -0.2 degrees, 25.2 + / -0.2 degrees, 27.2 + / -0.2 degrees and 28.9 + / -0.2 degrees. After the methylpyrazine derivative-piperazine eutectic crystal prepared by the method is placed in a solid state, the product is high in purity and good in stability, and animal experiments prove that the bioavailability is high. The eutectic crystal is simple in preparation process and has a good industrial application prospect.

Description

technical field [0001] The invention belongs to the technical field of organic drug co-crystals, in particular to a methylpyrazine derivative-piperazine co-crystal. Background technique [0002] Drug co-crystals are based on the principle of supramolecular chemistry, that is, molecular recognition and supramolecular self-assembly through intermolecular synergy. The active pharmaceutical ingredient (API) self-assembles with a suitable cocrystal former (CCF) through hydrogen bonds, or non-covalent bonds with saturation and directionality (such as van der Waals forces of aromatic hydrocarbons or benzene rings, π- π conjugation and halogen bond) to form a new structure, that is, drug co-crystal. It is based on hydrogen bonds, and neither needs to form new covalent bonds nor destroy existing covalent bonds. While retaining the pharmacological effects of the drug itself, it can also modify the physical and chemical properties of the drug, such as improving the Stability, reducin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/24C07D295/027A61P3/06A61K31/495A61K31/4965
CPCC07D241/24C07D295/027A61P3/06A61K31/495A61K31/4965C07B2200/13A61K2300/00
Inventor 翟立海夏祥来梁茂征杨丹
Owner LUNAN PHARMA GROUP CORPORATION
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