Effects of Viscous Hyaluronate–Sodium Solutions on the Nasal Absorption of Vasopressin and An Analogue
Effects of Viscous Hyaluronate–Sodium Solutions on the Nasal Absorption of Vasopressin and An Analogue
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DOI：
10.1023/a:1015894910416
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发表时间：
1991-04
影响因子：
3.7
通讯作者：
K. Morimoto;H. Yamaguchi;Y. Iwakura;K. Morisaka;Y. Ohashi;Y. Nakai
中科院分区：
文献类型：
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作者：
K. Morimoto;H. Yamaguchi;Y. Iwakura;K. Morisaka;Y. Ohashi;Y. Nakai
本文研究了不同平均分子质量的透明质酸钠粘性溶液对加压素及其类似物L-去氨基-8-D-精氨酸加压素(L-d-8-DAVP)鼻腔吸收的影响。相对分子质量大于3×10~5道尔顿的透明质酸溶液可促进AVP的鼻腔吸收，而相对分子质量为5.5×10~4道尔顿的透明质酸溶液不能促进AVP的鼻腔吸收。AVP和L-d-8-DAVP对鼻腔吸收的促进作用在0-1.5%(w/v)的范围内呈剂量依赖性。在较低pH条件下，该溶液可促进AVP的鼻腔吸收。AVP和L-d-8-DAVP在透明质酸溶液(分子量分别为1.4×106和2×106道尔顿)中经鼻给药的生物利用度分别是在缓冲溶液(pH 7.0)中给药的2倍和1.6倍以上。透明质酸溶液(分子量1.4×106道尔顿)对体外培养的兔鼻粘膜纤毛搏动频率无影响。因此，透明质酸溶液可作为AVP和L-d-8-DAVP的鼻腔给药载体。
The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, l-deamino-8-D-arginine vasopressin (l-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 × 105daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 × 104daltons were not effective. The enhancing effects on the nasal absorption of AVP and l-d-8-DAVP were dependent on the concentration in the range of 0–1.5% (w/v) hyaluronate (MW 1.4 × 106daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and l-d-8-DAVP in hyaluronate solutions (MW 1.4 × 106and 2 × 106daltons) increased more than 2- and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 × 106daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranesin vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and l-d-8-DAVP.