Abstract
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.
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