インスリンおよびカルシトニンの経鼻吸収に及ぼすアズレンスルホン酸ナトリウムの吸収促進効果

Abstract

The promoting effect of sodium guaiazulene-3-sulfonate (AZ) on nasal absorption of insulin and calcitonin was studied in rats. The promoting effect of AZ was compared with two established nasal absorption promoters i. e. sodium caprate(Na Cap) and glycyrrhetinic acid 3-O-monohemiphthalate disodium (GA-MHPh 2Na). The nasal absorption of insulin was estimated from plasma immunoreactive insulin and changes in glucose levels. Plasma glucose level was decreased by intranasal administration of 10 U/kg insulin with 1% AZ, The extent of total decrement of glucose level to control was 51% and comparable to that with 1% Na Cap. The addition of 1% AZ to the nasal formulations enhanced insulin bioavailability from 3.7% to 27.6%. The nasal absorption of salmon calcitonin was evaluated from serum calcitonin and changes in calcium levels. Serum calcium levels were de-creased by intranasal administration of 10 U/kg salmon calcitonin in the presence of two already known promoters as effectively as intramuscular administration of the same dose, The addition of 1% AZ also showed the same extent of decrease as these ; the extent of total decrement of serum calcium level to control was 26.6%. The optimum concentration of AZ was about 1%. Intranasal administration of 1% AZ alone hardly changed plasma glucose level and serum calcium level from control. Hence, promoting effect of AZ on nasal absorption of insulin and calcitonin was proved. These findings indicate that AZ can be safe and effective nasal absorption promoter of peptides.