Method of delivering insulin lispro

• US 5,970,973 A
• Filed: 04/29/1998
• Issued: 10/26/1999
• Est. Priority Date: 01/29/1993
• Status: Expired due to Fees

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Gonda, Igor, Rubsamen, Reid M.
• Primary Examiner(s): Lewis, Aaron J.
• Application Number:
  US09/069,721
• Time in Patent Office: 545 Days
• Field of Search: 222/95, 239/102.2, 239/145, 128/200.14, 128/200.22, 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 15/0066 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 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 drug delivery, comprising:

moving a formulation of insulin lispro through a flexible porous membrane comprising pores having a diameter in the range of from about 0.25 to about 6.0 microns wherein the membrane protrudes outward when the formulation is moved through the membrane thereby creating an aerosol; and

inhaling the aerosol.

2. The method of claim 1, wherein:

insulin lispro is present in a first compartment in a dry form, the first compartment having an opening therein which is covered by the 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.

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

4. The method of claim 3, wherein pores of the porous membrane have a conical 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.

5. The method of claim 1, wherein the formulation is aerosolized 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.

6. The method of claim 5, wherein the formulation is present in a container, comprising:

a wall which is collapsible upon the application of force and wherein the porous membrane covers an exit path from the container.

7. The method of claim 1, wherein the porous membrane comprises pores having a diameter in a range of about 0.25 to 3.0 microns.

8. The method of claim 1, wherein the pores have a diameter in range of from 0.25 to 1.5 microns.

9. The method of claim 1, wherein the formulation is aerosolized into a channel and the membrane protrudes into the channel.

10. The method of claim 1, further comprising:

measuring surrounding air humidity via a solid state hygrometer.

11. The method of claim 1, further comprising:

removing water vapor from inhaled air via a desicator.

12. The method of claim 1, further comprising:

evaporating carrier from aerosolized formulation via a heater.

13. The method of claim 1, further comprising:

ultrasonically vibrating the membrane via a vibrating device.

14. The method of claim 13, wherein the vibrating device is a prezoelectric ceramic crystal.

15. The method of claim 1, further comprising:

moving the formulation through the membrane via a piston.