Insulin delivery enhanced by coached breathing

• US 5,743,250 A
• Filed: 11/22/1996
• Issued: 04/28/1998
• 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:
  US08/754,423
• Time in Patent Office: 522 Days
• Field of Search: 128/200.14, 128/200.22, 128/200.23, 128/203.12, 128/204.23
• 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 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0055 the used dosages being coiled
• 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 2016/0036 in the breathing tube and used in both inspiratory and expiratory phase
• CPC Class Codes: A61M 2202/062 Desiccants
• CPC Class Codes: A61M 2202/064 : Powder
• CPC Class Codes: A61M 2205/50 : with microprocessors or computers
• 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 an inhale-exhale breathing maneuver. Particles of insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced 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 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 enhancing the rate at which insulin migrates into a patient'"'"'s circulatory system, comprising:

aerosolizing a formulation;

inhaling the aerosolized formulation into lungs of a patient and allowing particles of insulin to deposit on lung tissue;

inhaling maximally followed by exhaling the forced vital capacity of the lungs.

2. The method of claim 1, wherein the inhaling maximally and exhaling the forced vital capacity are measured.

3. The method of claim 2, wherein the measuring 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 1, wherein:

insulin is present in a first compartment as dry insulin, the first compartment having an opening therein which is covered by a flexible porous membrane with pores having a diameter of about 0.25 micron to about 6 microns; and

a carrier is present in a second compartment as a flowable liquid and the second compartment is connected to and in fluid connection with the first compartment, the fluid connection being interrupted by a membrane which is ruptured by the application of pressure.

5. The method of claim 1, wherein the formulation is a liquid formulation comprised of a pharmaceutically acceptable carrier and insulin and is present in a container with an opening which is covered by porous membrane.

6. The method of claim 5, wherein the pores have a cross-sectional configuration with a small end opening of 0.25 to 6.0 microns in diameter and a large end opening of 2 to 20 times the diameter of the small end.

7. A method of coaching a patient to enhance the rate of delivery of insulin deposited in the lungs of the patient, comprising:

administering insulin to the patient by inhalation; and

instructing the patient to inhale maximally followed by exhaling maximally.

8. The method of claim 7, further comprising:

determining the glucose level of the patient.

9. The method of claim 8, wherein the determining, inhaling and exhaling maximally are repeated in a manner so as to maintain the glucose level in a desired range.

10. The method of claim 8, wherein the inhaling maximally and exhaling maximally are measured.

11. The method of claim 10, wherein the measuring 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.

12. The method of claim 11, wherein the administering is carried out after measuring airflow through the 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.

13. The method of claim 12, further comprising:

repeating the measuring, determining and administering steps in a manner such that the administering repeatedly begins at substantially the same inspiratory flow rate and inspiratory volume.

14. The method of claim 12, further comprising:

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

15. The method as claimed in claim 14, wherein the administering of insulin and determining of the glucose level are continually recorded and adjustments are made in the amount of insulin administered based on the effect of insulin administration on the glucose levels of the patient.

16. The method as claimed in claim 17, wherein the amount of 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.

17. The method of claim 7, wherein the method is carried out using a drug delivery device, comprising:

a channel having a first opening into which air can be inhaled and a second opening from which a patient can withdraw air;

a mechanism for applying physical force to formulation upon actuation; and

an air-heating device which adds energy to air inhaled into the channel;

wherein the device is a hand-held self-contained device having a total weight of 1 kilogram or less.

18. The method of claim 17, wherein the formulation is present in a container, comprising:

a wall which is collapsible upon the application of force;

a porous membrane covering an exit path from the container, the porous membrane having pores with a diameter in the range of about 0.25 to about 6.0 microns.

19. The method of claim 7, further comprising:

orally administering a sulfonylurea drug to the patient.

20. The method of claim 19, wherein the sulfonylurea drug is selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolbutamide, glipzide and glyburide.