アミノ酸の経皮吸収性の向上に関する検討

Abstract

Amino acids are amphoteric electolytes and water-soluble compounds. In general, a water-soluble drug such as amino acid shows low skin permeability due to the barrier effects of the stratum corneum. To attempt to improve the percutaneous absorption of amino acid, we investigated the skin permeability of L-Phenylalanine and its ester derivatives as model compounds. L-Phenylalanine derivatives used in this study were L-Phenylalanine methyl ester, ethyl ester, t-butyl ester and benzyl ester. Excised hairless mouse skin was mounted between the donor and the receptor chamber of a skin-permeation apparatus. The compound that permeate through the skin was analyzed by HPLC. The permeability of L-Phenylalanine and its ester derivatives was calculated from the accumulated amount of the sample in the receptor chamber for the specific time period (2, 4, 6, 8, 24, and 28hr). The results showed that (1) the ester derivatives which permeated through the skin were detected as Phenylalanine and (2) the permeation rate of L-Phenylalanine, the methyl ester, the ethyl ester, the t-butyl ester, and the berizyl ester were 0.10, 7.22, 13.63, 22.51, and 16.88 μg/cm2/hr, respectively. All the ester derivatives showed higher permeability through the skin than that of L-Phenylalanine (71∼220 times). The results indicated that (1) the permeability of the derivatives depended on its ester type and (2) the esterification of L-Phenylalanine could improve its permeability through the skin. Since no derivative could be detected in the receptor chamber, the derivatives, which could permeate the stratum corneum, were hydrolyzed quickly by the esterase in skin tissue. Because the esterification of amino acids suppresses its ionization, enhances its hydrophobicity, and improves its permeability to skin tissue, the amino acid derivatives (e.g. ester form) is useful a.a prodrug that could be applied to skin.