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[摘要]:To prevent the precipitation reaction between glycyrrhizin (1) and berberine (3) in the decoctions of Glycyrrhiza/Coptis rhizome or Glyqyrrhiza/Phellodendron bark, the presence of cyclodextrin (CD) in the mixture was proven to be effective. The preventing effect decreased in the order gamma-CD > beta-CD, and no effect was observed for alpha-CD. On the other hand, the extraction degree of 1 from the natural medicine Glycyrrhia was considerably increased in the presence of gamma-CD, gamma-CD being much more effective than alpha- or beta-CD. Thus, the blocking effect of CD on the precipitate formation between I and 3 is suggested to be primarily dependent on the stability of the inclusion complex of the CD with 1. To establish the structure of such a preferred inclusion complex, the interactions of 1 with beta- and gamma-CDs were investigated by H-1-NMR spectroscopy and molecutar-dynamics (MD) calculations. The H-1-NMR measurements showed that the increase in solubility of 1 in H2O is dependent on the degree of its inclusion into the CD, which depends on the molecular size of the CD. The MD calculations suggested that the H-bond interactions are sufficiently strong to form a stable [1/gamma-CD] complex, in which the lipophilic rings C, D, and E of 1 are fully inserted into the molecular cavity of gamma-CD, thus forming a kind of structure covered by a hydrophilic molecular capsule, while such an interaction mode is impossible for alpha- or beta-CD. |
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