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用大鼠在体灌注法研究l-酪氨酸的鼻腔吸收以及结构改造对其吸收的影响。各种药物溶液循环通过鼻腔一小时,以一定间隔取样,用HPLC 法定量分析。结果表明,l-酪氨酸浓度在2.8×10~(-4)～2.22×10~(-3)M 时呈浓度依赖,而pH 为4和7.4时,鼻腔吸收的程度相同(约13%),吸收过程符合Michaelis-Menten 公式。因此,l-酪氨酸的鼻腔吸收是以两性离子形式进行的,吸收可能是介导的转运过程。影响肽类鼻腔吸收生物利用度低的主要因素可能是由于化合物的极性所致。鉴此,制备一系列以l-酪氨酸为代表的亲脂性肽类前药,并对结构上各种极性功能团对鼻腔吸收的影响进行探讨。
Nasal absorption of l-tyrosine and the effect of its structural modification on its uptake were studied by in-vivo perfusion in rats. Various drug solutions were circulated through the nasal cavity for an hour, sampled at regular intervals, and quantified by HPLC. The results showed that concentration of l-tyrosine was concentration-dependent at 2.8 × 10 -4 -2.22 × 10 -3 M, while nasal absorption was the same at pH 4 and 7.4 (about 13% ), The absorption process in line with Michaelis-Menten formula. Therefore, l-tyrosine nasal absorption is zwitterionic form, absorption may be mediated by the transport process. The main factor that affects the low bioavailability of nasal absorption of peptides may be due to the polarity of the compound. In view of this, a series of lipophilic peptide prodrugs represented by 1-tyrosine were prepared, and the influence of various polar functional groups on nasal absorption was discussed.