Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume

• US 20040089290A1
• Filed: 11/04/2003
• Published: 05/13/2004
• Est. Priority Date: 01/29/1993
• Status: Active Grant

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Farr, Stephen J., Gonda, Igor, Rubsamen, Reid M.
• Granted Patent: US 7,028,686 B2
• Time in Patent Office: Days
• 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 15/0043 Non-destructive separation of the package, e.g. peeling
• 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 15/0066 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
• CPC Class Codes: B05B 17/0607 : generated by electrical means, e.g. piezoelectric transducers

Abstract

Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.

Claims

1. A method of administering insulin to a human patient by inhalation, comprising:

(a) exhaling a determined volume of air;

(b) aerosolizing an insulin formulation

(c) inhaling the aerosolized formulation with a determined volume of air;

(d) repeating (a), (b) and (c) a plurality of times wherein the determined volume of air exhaled in (a) is substantially the same for each step (a) and the determined volume of air in (c) is substantially the same for each step (c).

2. The method of claim 1, wherein the exhaled volume of air in step (a) and inhaled volume of air in step (c) are determined by electronically measuring volume for each repeated step (a).

3. The method of claim 1, wherein the exhaled volume of air in step (a) is determined by the patient exhaling maxially for each repeated step (a) and the inhaled volume of air in step (c) is determined by the patient exhaling maximally for each repeated step (c).

4. The method of claim 1, further comprising:

(e) measuring the patient'"'"'s inspiratory flow rate;

(f) measuring the patient'"'"'s inspiratory volume; and

wherein aerosolizing in step (b) is repeatedly at substantially the same measured inspiratory flow rate and substantially the same measured inspiratory volume.

5. The method of claim 1, wherein the formulation is aerosolized in step (b) by moving the formulation through a porous membrane having pores with a diameter in the range of about 0.5 to 3.0 microns.

6. The method of claim 4, wherein the aerosolizing is repeatedly within a range of about 0.1 to about 2.0 liters/second and within a range of about 0.15 to about 0.80 liters.

7. The method of claim 1, wherein the determined inhaled volume is in the range of about 75% to about 100% of the patient'"'"'s total lung volume minus residual lung volume.

8. The method of claim 1, within the insulin formulation is a liquid flowable formulation.

9. The method of claim 1, wherein the insulin formulation comprises an active ingredient selected from the group consisting of human recombinant insulin and an insulin analog.

10. The method of claim 1, further comprising:

(e) determining the patient'"'"'s glucose level and adjusting the amount of insulin administered to obtain a desired glucose level.

11. The method of claim 8, further comprising:

heating air which contacts aerosolized formulation and evaporates liquid from aerosolized particles.

12. A drug delivery device, comprising:

a channel comprising a first opening into which air can be inhaled, a second opening from which air can be withdrawn and a third opening through which aerosolized particles enter the channel;

a container having a drug formulation therein;

adjustable means for applying different degrees of physical force to the formulation wherein the different degrees of force result in aerosolization of different amounts of formulation.

13. The device of claim 12, further comprising:

a disposable porous membrane through which the formulation is forced, the membrane having pores with a diameter of about 0.5 to 3 microns; and

a means for moving disposable membranes into a drug release position for use in aerosolization and out of the drug release position after use;

wherein the means for applying different degrees of force is adjustable to provide degrees of force which correspond to set amounts of formulation which will be expelled from the container by the force.

14. The device of claim 12, further comprising:

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

15. The device of claim 12, wherein the drug formulation is an insulin formulation.

16. The device of claim 12, wherein the device is a hand-held, self-contained device having a total weight of less than one kilogram.

17. The device of claim 12, wherein the adjustable means for applying force is selected from the group consisting of a piston, a cam, and a vibration device.

18. The device of claim 12, further comprising:

a desiccator positioned in the channel at a point after the first opening and prior to the second and third opening in a direction of flow from the first opening to the second opeining and then to the third opening.

19. The device of claim 12, further comprising:

a means for blocking air flow to the second opening.

20. The device of claim 19, further comprising:

a means for actuating the means for blocking air in response to a pre-set volume of air measured.