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We previously compared hypoglycemic responses after the instillation of insulin formulations. A hypoglycemic response was actually observed after an instillation of insulin with ophthalmic preservatives. In the present study, in order to evaluate the usefulness of insulin formulation containing ophthalmic preservatives, a serum concentration of insulin and an irritation to the eye were investigated after instillation of the insulin formulation in albino rabbits. The ophthalmic preservatives used were benzalkonium chloride, paraben, 2-phenylethanol, benzyl alcohol and sorbic acid. As a result, ophthalmic preservatives, especially benzalkonium chloride and paraben, increased the serum concentration of insulin. The insulin concentration showed a significant correlation with the hypoglycemic response reported previously. This result indicates that ophthalmic preservatives increase the absorption of ocularly applied insulin, and the absorbed insulin decreases serum glucose concentration. The insulin formulation with preservatives showed little irritation on rabbit eyes according to blinking measurements. These results indicate that ophthalmic preservatives are useful for the systemic delivery of ocularly applied insulin.

Effect of Ophthalmic Preservatives on Serum Concentration and Local Irritation of Ocularly Applied Insulin.