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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.

We studied the promoting effect of glycyrrhetinate and its derivatives on nasal absorption of insulin in rats. These derivatives can be divided into two groups based on mother structural skeleton. One group is 3-O-ester derivatives of glycyrrhetinate and the other group is 3-O-and 30-O-ester derivatives of a hydrogenated glycyrrhetinate analog. The former group consists of G2 2K, GA Na, GA-MHS 2Na and GA-HPh 2Ha and the latter group consists of DG-DHPh 2Na, HomAD-DHPh 2Na and HetAD-DHPh 2Na. These derivatives significantly promoted nasal absorption of insulin and decreased plasma glucose levels in rats. We found that the optimum concentration of these derivatives such as GA-MHS 2Na, GA-HPh 2Na and DG-DHPh 2Na was about 1%. The promoting effect of glycyrrhetinic ester groups on nasal absorption of insulin in rats is GZ 2K < GA Na < GA-MHS 2Na < GA-HPh 2Na. These results indicated that strength of the promoting effect differed by 3-O-ester groups. On the other hand, hydrogenated glycyrrhetinic ester analogs were more effective than the glycyrrhetinic ester group. Particularly, DG-DHPh 2Na and HomAD-DHPh 2Na were significantly promoted nasal absorption of insulin in rats, and bioavailability in the presence of these promoters was comparable to that following intravenous injection. It is indicated that glycyrrhetinate and its derivatives can be applicable to promotion of nasal absorption of insulin.