Oral drug composite of beta-cyclodextrin edaravone inclusion and preparation method thereof

Abstract

The invention relates to an oral drug composite of beta-cyclodextrin edaravone inclusion, comprising the compositions in parts by weight: 1 part of edaravone and 6-100 parts of cyclodextrin. Based on the optimization scheme, the mass ratio of the edaravone and the cyclodextrin is 1:6-50, wherein the mass ratio of beta-cyclodextrin to the cyclodextrin is 1:6-20, and the mass ratio of mixed cyclodextrin containing the beta-cyclodextrin is 1:8-50. A preparation method comprises the following steps of mixing the beta-cyclodextrin or the mixed cyclodextrin containing the beta-cyclodextrin with 1-5 times mass of water, adding the edaravone with the selected mass ratio or adding a solution prepared from the edaravone and 10 times soluble organic solvent, grinding or stirring, vaporizing and eliminating water at the temperature no higher than 60 DEG C, and decompression drying to obtain a white powdery inclusion complex. A contrast test is carried out on the invention and edaravone injection on sale, the absolute bioavailability of an inclusion complex preparation thereof can reach above 55 percent; and compared with a common edaravone suspension preparation (attached drawing 6), the relative bioavailability of the invention reaches up to about 1000 percent.

Description

technical field [0001] The invention relates to a pharmaceutical composition, in particular to an oral edaravone pharmaceutical composition and a preparation method of the pharmaceutical composition. technical background [0002] Edaravone, trade name: Bicun, chemical name: 3-methyl-1-phenyl-2-pyrazolin-5-one (3-methyl-1-phenyl-2-pyrazolin-5 -one), molecular formula: C 10 h 10 N 2 O, molecular weight: 174.2; Structural studies show that the Edaravone molecules of aromatic heterocycles have different configurations under different solvent conditions (I.Braz.Chem.Soc., 2008, 19(6): 1207~1214 ), Edaravone in DMSO with strong polarity is 1,2-dihydropyrazolone structure (a, attached figure 1 ), and in the hydrophobic chloroform solution is a single 2,4-dihydropyrazolone configuration (b, attached figure 1 ); the difference between the two ketone structures a and b is that the nuclear magnetic resonance spectrum of its a has =CH-proton peak at δ=5.36, while b appears-CH at δ=...

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Problems solved by technology

[0005] Sato T. etc. took the hydroxypropyl-β-cyclodextrin / edaravone solution of pH 4.5 as the test sample, and did not verify whether there is effective inclusion in the hydroxypropyl-β-cyclodextrin / edaravone in the solution. Whether it can form a stable clathrate or not, there is no easy-to-use and easy-to-carry solid clathrate. The solution needs to add a variety of additives to have a certain oral absorption. Therefore, its hydroxypropyl-β - The use of cyclodextrin has not achieved practical application value

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