Title:  Method for administering acylated insulin

United States Patent:  6,335,316

Assignee:  Eli Lilly and Company (Indianapolis, IN)

Filed:  March 10, 2000

The invention relates to a method of administering a fatty acid-acylated insulin or insulin analog by inhalation, a method for treating diabetes by administering a fatty acid-acylated insulin or insulin analog by inhalation, and a method for treating hyperglycemia by administering a fatty acid-acylated insulin or insulin analog by inhalation.

SUMMARY OF THE INVENTION

The present invention is a method for administering long-acting, soluble insulin by inhalation. The invention also encompasses the use of a fatty acid-acylated human insulin or a fatty acid-acylated insulin analog in the manufacture of a medicament for the treatment of diabetes or hyperglycemia by inhalation, which treatment comprises administering to a patient in need thereof an effective amount of the medicament using an inhalation device, such that the medicament is deposited in the lungs of the patient. The present invention solves two problems currently not addressed by the art. First, previous pulmonary methods for delivering insulin do not provide adequate time action to control blood glucose between meals and overnight. Second, presently known soluble, long-acting insulins and insulin derivatives are delivered by subcutaneous injection, which involves the inconvenience of preparing a sample for injection, and the pain of a needle-stick. According to the present invention, a patient in need of insulin to control blood glucose levels will achieve advantageous slow uptake and prolonged persistence in the blood of-acylated insulin compared to inhalation of non-acylated insulin, and reduced inconvenience and pain compared with subcutaneous delivery. Preferably, the acylated insulin is delivered to the lower airway of the patient. The acylated insulin can be delivered in a carrier, as a solution or suspension, or as a dry powder, using any of a variety of devices suitable for administration by inhalation. The acylated insulin can be administered using an inhalation device such as a nebulizer, a metered-dose inhaler, a dry powder inhaler, a sprayer, and the like. Preferably, the acylated insulin is delivered-in a particle size effective for reaching the lower airways of the lung, preferably less than about 10 microns mass median aerodynamic diameter (MMAD), preferably about 1 to about 5 microns MMAD, and more preferably about 1 to about 3 microns MMAD or from about 1 to about 2 microns MMAD, and most preferably from about 2 to about 3 microns MMAD. Preferred acylated insulins include a fatty acid-acylated insulin and a fatty acid-acylated insulin analog. The invention also provides a method for administering acylated insulin or acylated insulin analog together with insulin or insulin analog to a patient in need thereof by inhalation. Administering such combinations of acylated and un-acylated insulins provides both post-prandial and basal control of blood glucose levels. Because the method avoids injections, patient comfort is improved, and patient compliance increased compared with conventional insulin delivery methods.

Claim 1 of 47 Claims

We claim:

1. A pharmaceutical formulation comprising a fatty acid-acylated human insulin or a fatty acid-acylated human insulin analog and a liquid carrier, for administration by inhalation to a patient in need thereof.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.