Method of Use of Monomeric Insulin as a Means for Improving the Reproducibility of Inhaled Insulin

Abstract

The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be used to control the point of drug release.

1 .- 20 . (canceled)  
     
     
         21 . A method of treating a diabetic patient, comprising: 
 (a) aerosolizing a formulation comprising insulin lispro and a carrier to make an aerosol;    (b) inhaling a volume of the aerosol into a patient's lungs, thereby obtaining a maximum insulin lispro concentration (C MAX ) for the patient in a time needed to obtain a maximum concentration (T MAX ) for the patient wherein said C MAX  and T MAX  are less affected by an amount of air inhaled during inhalation of or after aerosolizing the formulation as compared to an effect on C MAX  and T MAX  obtained with a formulation of regular hexameric recombinant insulin;    (c) measuring the patient's inspiratory flow rate and inspiratory volume; and (d) repeatedly aerosolizing the formulation at the same measured inspiratory flow rate and inspiratory volume as measured in step (c); and (e) maintaining serum glucose levels in the patient in a range of greater than 60 mg/dl and less than 125 mg/dl.    
     
     
         22 . The method of  claim 21 , wherein the formulation is aerosolized by being moved through a porous membrane.  
     
     
         23 . The method of  claim 22 , wherein pores of the membrane have a diameter in the range of from 0.25 to 3.0 microns.  
     
     
         24 . The method of  claim 23 , wherein the pores have a diameter of from 0.25 to 1.5 microns.  
     
     
         25 . The method of  claim 21 , wherein the formulation is repeatedly aerosolized at an inspiratory flow rate in a range of from about 0.1 to about 2.0 liters/second.  
     
     
         26 . The method of  claim 21 , wherein the formulation is repeatedly aerosolized at an inspiratory volume of from about 0.1 to about 1.5 liters.  
     
     
         27 . The method of  claim 21 , wherein the formulation is repeatedly aerosolized at the same measured inspiratory flow rate in the range of 0.1 to 2.0 liters/second and separately determined inspiratory volume with delivery beginning in a range of 0.15 to 1.5 liters wherein inspiration is continued to a maximum.  
     
     
         28 . The method of  claim 21 , wherein the monomeric insulin is insulin lispro in a zinc salt form.  
     
     
         29 . The method of  claim 21 , wherein the formulation is an aqueous solution.  
     
     
         30 . The method of  claim 21 , wherein the formulation is a dry powder.