Co-crystal of 5-fluorouracil and proline and preparation method of co-crystal

A technology of fluorouracil and proline, which is applied in the drug co-crystal of 5-fluorouracil and proline and its preparation field, can solve the problems of affecting the curative effect, poor solubility of 5-fluorouracil, etc., and achieves a simple and easy preparation method with low cost , the effect of mild reaction conditions

Inactive Publication Date: 2018-08-07
OCEAN UNIV OF CHINA
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  • Abstract
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  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the course of clinical use, it was found that the poor solubility of 5-fluorouracil affected its curative effect to a certain extent.

Method used

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  • Co-crystal of 5-fluorouracil and proline and preparation method of co-crystal
  • Co-crystal of 5-fluorouracil and proline and preparation method of co-crystal
  • Co-crystal of 5-fluorouracil and proline and preparation method of co-crystal

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specific Embodiment approach 1

[0020] Specific implementation mode 1: The structural formula of the 5-fluorouracil-proline cocrystal in this embodiment is [2C 4 h 3 N 2 o 2 F·C 5 h 9 NO 2 ], which consists of two 5-fluorouracil molecules and one proline molecule as the basic structural unit. The 5-fluorouracil-proline cocrystal is monoclinic, and the space group is P 2 1 / n, the unit cell parameters are: a = 4.957 Å, b = 10.867 Å, ​​c = 28.481 Å, α = 90.00°, β = 91.323°, γ = 90.00°. Its PXRD characteristic diffraction peaks appear at 8.652°, 16.601°, 17.578°, 19.642°, 20.403°, 24.875°, 26.997°, 28.067°.

[0021] The 5-fluorouracil-proline co-crystal described in this embodiment consists of two 5-fluorouracil molecules and one proline molecule bonded together through hydrogen bonds. Such as figure 1 As shown, the proline molecule connects two 5-fluorouracil molecules together through hydrogen bonds N3-H3...O5 and hydrogen bonds N1-H1...O6 to form a basic structural unit. In the 5-fluorouracil-proli...

specific Embodiment approach 2

[0022] Specific embodiment two: the preparation method of the present embodiment 5-fluorouracil-proline co-crystal is implemented according to the following steps:

[0023] Put the 5-fluorouracil raw material and proline in a round-bottomed flask with a molar ratio of 2:1, add ethanol into the round-bottomed flask, heat and stir in a water bath at 30 °C for 2-3 h, then filter, and let the filtrate stand for volatilization The solid phase was collected in 2-4 days to obtain 5-fluorouracil-proline co-crystal.

specific Embodiment approach 3

[0024] Embodiment 3: This embodiment differs from Embodiment 2 in that the solid-to-liquid ratio of the mixed powder to ethanol is (0.1-0.15) g: (4-6) mL, and other steps and parameters are the same as Embodiment 2.

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Abstract

The invention provides a pharmaceutical co-crystal of 5-fluorouracil and proline and a preparation method of co-crystal and relates to the pharmaceutical co-crystal field. The co-crystal is [2C4H3FN2O2.C5H9NO2], and a basic structural unit is formed by virtue of two 5-fluorouracil molecules and a proline molecule. The co-crystal is of a monoclinic system, and the space group of the co-crystal is P21/n. The pharmaceutical co-crystal is prepared from 5-fluorouracil and proline by virtue of a solvent evaporation method and a cooling method. According to the pharmaceutical co-crystal, the solubility of 5-fluorouracil is improved, and a foundation is laid for the increase of bioavailability and the improvement of the pesticide effect of 5-fluorouracil. The preparation method of the pharmaceutical co-crystal is simple, feasible, low in cost and convenient for large-scale popularization in pharmaceutical industry.

Description

technical field [0001] The invention relates to the field of drug co-crystals, in particular to a drug co-crystal of 5-fluorouracil and proline and a preparation method thereof. Background technique [0002] In the modern pharmaceutical industry, after many candidate drugs have gone through layers of clinical trials, only less than one percent of the drugs finally appear on the market. Poor physical and chemical properties are one of the main reasons why drugs cannot be marketed. In order to improve the physicochemical properties of these drugs, researchers have adopted various methods, including drug co-crystals. Pharmaceutical co-crystals are co-crystals formed by combining pharmaceutical active ingredients and physiologically acceptable co-crystal formers in the same crystal lattice in a certain stoichiometric ratio in the form of hydrogen bonds and other non-covalent bonds according to the principles of crystal engineering. Drug co-crystals can have a huge impact on the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/553C07D207/16
CPCC07B2200/13C07D207/16C07D239/553
Inventor 李延团刘方张美娇焉翠蔚管华诗
Owner OCEAN UNIV OF CHINA
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