Method of treating diabetes mellitus in a patient

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 . A method of improving reproducibility of insulin delivered by inhalation, comprising:
 aerosolizing a formulation comprising insulin;   inhaling the aerosolized formulation into the lung of a patient after which the insulin rapidly disassociates into monomeric insulin.   
   
   
       2 . The method of  claim 1 , wherein the insulin is formulated to enhance disassociation of the insulin into monomeric form. 
   
   
       3 . The method of  claim 1 , wherein the formulation is a liquid. 
   
   
       4 . The method of  claim 1 , wherein the formulation is a dry powder. 
   
   
       5 . The method of  claim 4 , wherein enhanced disassociation of insulin to monomeric form is obtained by a salt form of insulin used in the formulation. 
   
   
       6 . The method of  claim 5 , wherein the inhaling is carried out with different inhaled volumes of air while maintaining essentially the same blood concentration versus time profile in terms of affect on glucose level. 
   
   
       7 . (canceled) 
   
   
       8 . The method of  claim 5 , wherein the salt form is sodium insulin. 
   
   
       9 . The method of  claim 8 , further comprising:
 orally administering a sulfonylurea drug to the patient.   
   
   
       10 . The method of  claim 9 , wherein the sulfonylurea drug is selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolbutamide, glipzide and glyburide. 
   
   
       11 . A method of enhancing the rate at which an inhaled drug migrates into a patient's circulatory system, comprising:
 aerosolizing a dry powder formulation comprised of a insulin;   inhaling the aerosolized formulation into lungs of a patient and allowing particles of the insulin to deposit on lung tissue after which the insulin rapidly disassociates into monomeric insulin.   
   
   
       12 .- 13 . (canceled) 
   
   
       14 . The method of  claim 11 , wherein the aerosol comprises particles having a diameter in the range of about 1.0 to about 4.0 microns. 
   
   
       15 . The method of  claim 11 , further comprising:
 repeating the aerosolizing and inhaling a plurality of times.   
   
   
       16 . The method of  claim 15 , wherein the dry powder formulation is aerosolized by mechanical movement. 
   
   
       17 .- 18 . (canceled) 
   
   
       19 . The method of  claim 11 , further comprising:
 repeating the aerosolizing, and inhaling a plurality of times while obtaining substantially the same total inhaled volume for each delivery.   
   
   
       20 . The method of  claim 19 , wherein the aerosolizing and inhaling are repeatedly carried out at substantially the same inspiratory flow rate and inspiratory volume.