Method of maintaining a diabetic patient's blood glucose level in a desired range

• US 5,873,358 A
• Filed: 04/29/1998
• Issued: 02/23/1999
• Est. Priority Date: 01/29/1993
• Status: Expired due to Term

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Gonda, Igor, Rubsamen, Reid M.
• Primary Examiner(s): Lewis, Aaron J.
• Application Number:
  US09/069,891
• Time in Patent Office: 300 Days
• Field of Search: 128/200.14, 128/200.22, 128/200.23, 128/203.12
• US Class Current: 128/200.14
• CPC Class Codes: A61J 7/0418 with electronic history memory
• CPC Class Codes: A61J 7/0427 with direct interaction with a dispensing or delivery system
• CPC Class Codes: A61J 7/0445 for preventing drug dispensing during a predetermined time period
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/0031 by bursting or breaking the package, i.e. without cutting or piercing
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0066 with means for varying the dose size
• CPC Class Codes: A61M 15/008 Electronic counters
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 16/142 with semi-permeable walls separating the liquid from the respiratory gas
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2202/062 Desiccants
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/8206 battery-operated

Abstract

The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient'"'"'s lungs and the rate at which the insulin is absorbed into the blood is increased by the use of monomeric insulin and/or an inhale-exhale breathing maneuver. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by the monomeric form of insulin and by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulin or insulin analog 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. The sensor can also assist the patient in the inhale-exhale maneuver.

Claims

1. A method of maintaining a diabetic patient'"'"'s blood glucose level within a desired range, comprising:

determining the glucose level of a patient;

administering aerosolized monomeric insulin to the patient by inhalation instructing the patient to inhale maximally followed by exhaling maximally; and

repeating the determining and administering a plurality of times over a period of time so as to maintain a desired glucose level in the patient;

wherein the administering of monomeric insulin and determining of the glucose level are continually recorded and adjustments are made in the amount of monomeric insulin administered based on the effect of monomeric insulin administration on the glucose levels of the patient; and

wherein the amount of monomer insulin administered is in the range of 1 unit per day to 50 units per day and wherein the desired serum glucose level in the patient is within the range of 50 mg/dl to 300 mg/dl.

2. The method of claim 1, further comprising:

measuring the inhaling maximally and exhaling maximally.

3. The method of claim 2, wherein the monomeric insulin is insulin lispro and the measuring of the inhaling maximally and exhaling maximally is carried out electronically and a first signal is sent after the inhaling reaches a desired point and a second signal is sent after the exhaling reaches a desired point.

4. The method of claim 3, wherein the administering is carried out after measuring airflow through a channel and determining inspiratory flow rate and inspiratory volume;

and

determining a beginning point to force formulation through pores of a porous membrane based on real time measured values of inspiratory flow rate and inspiratory volume.

5. The method of claim 4, wherein the determining and administering steps are carried out in a manner such that the administering repeatedly begins at substantially the same inspiratory flow rate and inspiratory volume.

6. The method of claim 1, further comprising:

orally administering a sulfonylurea drug to the patient.

7. The method of claim 6, wherein the sulfonylurea drug is selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolbutamide, glipzide and glyburide.