Method of treating diabetes mellitus in a patient

• US 7,448,375 B2
• Filed: 05/17/2005
• Issued: 11/11/2008
• Est. Priority Date: 01/29/1993
• Status: Expired due to Fees

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Farr, Stephen J., Gonda, Igor, Rubsamen, Reid M.
• Primary Examiner(s): Douglas; Steven O
• Application Number:
  US11/130,986
• Publication Number:
  US 20050274377A1
• Time in Patent Office: 1,274 Days
• Field of Search: 128/200.14, 128/200.22, 128/200.23, 128/203.12, 128/203.15
• US Class Current: 128/200.14
• CPC Class Codes: A61M 11/001 Particle size control
• 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 15/0081 Locking means
• CPC Class Codes: A61M 15/0083 Timers

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 treating diabetes in a patient who in the absence of treatment cannot maintain an acceptable blood-glucose level, the method comprising the steps of:

providing an individual dosage of insulin in dry powder form to a handheld inhalation delivery device having a mouth piece;

completing an exhalation;

aerosolizing the insulin in with a volume of air so as to form a suspension of insulin and air and

inhaling the aerosolized insulin suspension with a high volume of air (H), wherein the high volume of air (H) comprises the suspension of insulin and air, as well as a volume of air following the introduction of the air and insulin suspension into the respiratory tract of the patient, wherein the high volume of air (H) is achieved by inhaling fully, wherein the inhaling of the insulin with the high volume of air (H) causes a dose of insulin to be transported to the alveoli region of the lungs for transport into the patients bloodstream in a controlled and repeatable manner so as to maintain an acceptable blood-glucose level in the patient; and

repeating the above steps as needed to maintain an acceptable blood-glucose level, wherein when the steps are repeated the insulin and air suspension is introduced to the respiratory tract of the patient at substantially the same inspiratory volume each time the inhaling step is repeated and wherein for each repetition of exhaling substantially the same volume is exhaled and wherein for each repetition for inhaling, substantially the same high volume of air (H) is inhaled.

2. The method of claim 1, wherein the inhaling step is performed at an inspiratory flow rate in the range of 0.1 to 2 liters per second.

3. The method of claim 2, wherein the insulin and air suspension is inhaled after inhaling an initial volume of air and wherein the inhaling is continued after inhaling the aerosolized insulin.

4. The method of claim 2, wherein the introduction of the insulin and air suspension into the patient'"'"'s respiratory tract is begun prior to the patient reaching an inhaled volume of 0.8 liters.

5. The method of claim 1, wherein substantially all of the insulin and air suspension is introduced into the patient'"'"'s respiratory tract prior to the patient reaching an inhaled volume of 0.8 liters.

6. The method of claim 2, wherein the insulin particles suspended in the air that forms the aerosol have a velocity of equal to or less than the breath speed during the inhaling of the particles thru the mouth piece.

19. The method of claim 1, wherein the insulin powder consists essentially of human insulin.

20. The method of claim 5, wherein the insulin powder consists essentially of human or analog insulin.

7. A method of administering a controlled and reproducible dose of insulin to the bloodstream via the alveoli region of a diabetic patient'"'"'s lungs that is sufficient to control the patient'"'"'s blood-glucose levels, the method comprising the steps of:

supplying a predetermined amount of dry insulin powder to a handheld inhalation delivery device, wherein the device comprises a mouth piece thru which the patient inhales, and wherein the amount of dry insulin powder is in excess of the amount need to be absorbed into the blood of the patient to control the patient'"'"'s blood glucose levels;

creating an aerosol comprised of insulin particles by contacting the insulin with a volume of air, wherein the aerosol of particles has a velocity of −

2.0 to 2.0 liters per second, wherein negative velocity indicates that the particles are moving away from the patient and wherein positive velocity indicates that the particles are moving in a direction toward the patent thru the mouth piece;

exhaling a volume of air;

inhaling the particles after the particles have reached a speed less than the speed of the inhalation wherein the inhalation occurs at a rate less than 2 liters per second and wherein the inhaling occurs with a high volume of air (H), wherein the inhaling causes a percentage of the particles to reach the alveoli region of the patients lungs and wherein the inhaling cause the lungs to transport a controlled amount of the insulin to the patient'"'"'s blood stream; and

repeating the above steps, wherein for each repetition of the inhaling and exhaling substantially the same volume is exhaled each time and substantially the same volume is inhaled each time.

8. The method of claim 7, wherein the high volume of air (H) of air is determined by instructing the patient to inhale fully.

9. The method of claim 7, wherein the insulin and air suspension is created by combining 15000 ml volume of air with the insulin powder and wherein after the 15000 ml of air and insulin are inhaled, the patient continues to inhale to a determined point.

10. The method of any of claims 7, wherein the insulin powder consists essentially of human insulin.

11. The method of claim 7 wherein the insulin powder consists essentially of human insulin.

21. The method of claim 9, wherein the insulin powder consists essentially of luiman or analog insulin.

12. A method of administering a therapeutic dose of insulin that will create an acceptable blood-glucose level in a patient with diabetes that would not otherwise be able to achieve a normal blood glucose level absent medical treatment, the method comprising the steps of:

exhaling a volume of air;

aerosolizing a dry powder insulin with air to produce an aerosol of insulin particles suspended in a volume of air wherein the volume of air and aerosol is in the range of 0.05 to 2 liters;

inhaling the aerosolized particles with the volume of air in which they are suspended, followed by continuing to inhale until a high volume of air (H) has been inhaled, the high volume of air (H) being achieved by instructing the patient to inhale fully to a determined point in an inhalation cycle, thereby causing a controlled dose of insulin to be transported to the patient'"'"'s blood across the peripheral lung, wherein the absorbed dose of insulin causes the patient'"'"'s blood glucose level to be within an acceptable range; and

repeating the above steps at a later point in time wherein when the steps are repeated substantially the same high volume of air (h) is inhaled with each inhalation and wherein additional dose(s) of insulin are absorbed by the patient so as to maintain an acceptable blood glucose level.

13. The method of claim 12, wherein the dry powder insulin consists essentially of human or analog insulin and wherein it aerosolizes into an aerosol comprising particles of less than 10 microns.

14. The method of claim 13, wherein the insulin aerosol is inhaled at substantially the same point of an inspiratory cycle for each repetition of the inhaling step.

15. The method of claim 14, wherein the exhaling step comprises exhaling a determined volume of air and for each repetition of the exhaling step, substantially the same determined volume is exhaled.

16. The method of claim 14, wherein the aerosol comprises particles having a diameter of less than 6 microns and wherein the particles have a velocity of substantially zero in the absence of the flow created by the patients inhalation.

17. The method of claim 14, wherein the aerosol comprises particles having a diameter of less than 6 microns and wherein the aerosol of particles has a velocity of −

2 to +2 liters per second.

18. The method of claim 13, wherein the insulin consists essentially of human insulin.