Method for treating diabetes mellitus in a patient

• US 7,278,419 B2
• Filed: 01/30/2004
• Issued: 10/09/2007
• Est. Priority Date: 01/29/1993
• Status: Expired due to Fees

• Current Assignee: Aradigm Corporation
• Original Assignee: Novo Nordisk A/S
• Inventors: Farr, Stephen J., Gonda, Igor, Rubsamen, Reid M.
• Primary Examiner(s): MITCHELL, TEENA KAY
• Application Number:
  US10/768,371
• Publication Number:
  US 20040182383A1
• Time in Patent Office: 1,348 Days
• Field of Search: 128/200.14, 128/200.22, 128/200.23, 128/203.12, 128/203.15, 128/203.21, 128/200.24, 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: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• 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 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• 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 delivering aerosolized insulin. Repeatability of dosing is obtainable by using either regular insulin or monomeric insulin. When delivering insulin (not monomeric) by inhalation, the total inhaled volume should be about the same at each delivery to obtain repeatable results. The patient can be coached (by teaching) to inhale a given amount of air and can also be coached (by teaching) to inhale at a given flow rate. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. A dry powder or a liquid insulin formulation is delivered to the patient from a mechanical or electronic hand-held, self-contained device.

Claims

1. A method of treating diabetes mellitus in a diabetic patient in need thereof, by reproducibly dosing insulin for systemic effect to the patient'"'"'s circulatory system via the patient'"'"'s lungs in order to obtain an acceptable blood glucose level in the diabetic patient thereby reducing or eliminating the need for injection of insulin in the diabetic patient, said method comprising:

(a) supplying a predetermined amount of powdered insulin to a hand held device, said predetermined amount being in excess of that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient;

(b) exhaling;

(c) contacting said insulin with a compressed gas to form a cloud in said hand held device, said cloud comprising a repeatable amount of insulin, said repeatable amount being in excess of that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient, said cloud comprising insulin particles in the range between 0.5 and 6 microns; and

(d) inhaling said cloud at an inspiratory flow rate in the range of 0.1 to 2.0 liters per second and wherein the inhaling of said cloud occurs with a high volume that comprises 65% to 100% of the patient'"'"'s total lung volume;

(e) producing an acceptable blood glucose level in the diabetic patient, wherein the acceptable blood glucose level is produced by systemically absorbing a controlled dose of insulin that comprises a percentage of the supplied amount of powdered insulin.

2. The method of claim 1, wherein the inhalation in the inhaling step is performed by making a maximal effort to inhale.

3. The method of claim 1, wherein the aerosol is comprised of human insulin particles between about 1 and 4 microns and occurs with a pressure less than 400 psi.

4. The method of claim 1 wherein the patient is a patient with type II diabetes, and wherein the insulin cloud comprises human insulin particles having a size in the range of about 1-3 microns.

5. The method of claim 1, further comprising repeating steps a-e, wherein in each repetition of steps a-e, the patient inhales substantially the same volume of air with the cloud of insulin.

6. The method of claim 5, wherein the inhaling occurs at substantially the same flow rate.

7. The method of claim 1, further comprising the step of performing a breath hold for a predetermined period of time immediately after the inhaling step.

8. The method of claim 1, wherein the insulin is human insulin.

9. A method of treating diabetes mellitus in a patient in need thereof, by administering insulin replacement therapy for systemic effect delivered by inhalation in order to eliminate or reduce the need for injections of insulin, said method comprising:

supplying a predetermined amount of powdered insulin to a mechanical hand held device, said predetermined amount being in excess of that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient;

contacting said insulin with a compressed gas to form a cloud in a given area of said hand held device, said cloud comprising a repeatable amount of insulin, said repeatable amount being in excess of that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient, said cloud comprising insulin particles in the range between 0.5 and 6 microns;

exhaling a determined volume of air;

inhaling said cloud at an inspiratory flow rate in the range of 0.1 to 2.0 liters per second and wherein the inhaling of said cloud occurs with a high volume that comprises 65% to 100% of the patient'"'"'s total lung volume;

producing an acceptable blood glucose level in the patient, wherein the acceptable glucose level is produced by systemically absorbing a controlled dose of insulin that comprises a percentage of the supplied amount of powdered insulin;

repeating the above steps when the patient'"'"'s blood glucose levels rise or are expected to rise above a predetermined range and wherein for each repetition of the inhalation, the patient inhales substantially the same total volume.

10. The method of claim 9, wherein the insulin cloud is administered to the patient at substantially the same point of inspiration each time the inhaling step is repeated and wherein the patient continues to inhale after the cloud is inhaled and wherein the inhalation continues to a determined point in the inspiratory cycle that is substantially the same each time the inhaling step is repeated.

11. The method of claim 9, further comprising the step of performing a breath hold for a predetermined period of time immediately after the inhaling step.

12. The method of claim 9, wherein the insulin is human insulin.

13. A method of administering a controlled and repeatable dose of insulin to a diabetic patient that is sufficient to control the patient'"'"'s blood glucose level, the method comprising the steps of:

supplying a predetermined amount of dry insulin powder to a hand held mechanical inhalation device;

contacting the powder with a volume of air in a given area of the hand held device to form a standing cloud comprised of human insulin particles and air in the given area of the hand held device;

exhaling a volume of air;

inhaling the insulin and air cloud, followed by continual inhalation with additional air until a determined point of inspiration is reached, wherein the point is a point V_(h) corresponding to a high volume and wherein it is determined by coaching (by teaching) the patient to inhale to high volume, which corresponds to 65% to 100% of total lung volume;

wherein when the above steps are repeated in order to administer subsequent doses of insulin the patient, as a result of the coaching, inhales each subsequent dose with about the same high volume by inhaling to about the same determined point V_(h).

14. The method of claim 13, wherein the determined point is determined by making a maximal effort to inhale.

15. The method of claim 13, wherein the exhaled volume is a determined volume and when the steps are repeated in order to administer subsequent doses each determined volume of exhaled air is substantially the same.

16. The method of claim 15, wherein the flow rate during inhalation is maintained at a rate of under 2 liters per second, and wherein the inhaling step is immediately followed by a breath holding step that comprises performing a breath hold for a predetermined period of time.

17. The method of claim 16, wherein the flow rate during inhalation is substantially the same for each repetition of the inhalation.

18. The method of claim 15, wherein the insulin cloud is inhaled before the patient inhales 0.8 liters of air.

24. The method of claim 13, further comprising the step of performing a breath hold for a predetermined period of time immediately after the inhaling step.

19. The method of 18, wherein the total inhaled volume during the inhalation step is a determined volume that is determined by coaching the patient to perform a specific breathing maneuver.

20. The method of claim 19, wherein the specific maneuver comprises inhaling with a maximal effort.

21. The method of claim 19, wherein the inhaling occurs at a flow rate under about 1 liters per second and wherein the flow rate for each repetition of the inhaling step is substantially the same.

22. The method of claim 21, wherein the inhaling of the insulin cloud occurs at substantially the same accumulated inspiratory volume for each repetition of the inhaling step, and wherein the method further comprises a breath holding step immediately after the inhaling step and wherein for each repetition the breath holding step comprises holding of breath for substantially the same predetermined period of time.

23. The method of claim 22, wherein the determined point in each repetition of the inhaling step results in a determined volume being inhaled wherein the determined volume is substantially the same for each inhaling step and wherein the determined volume is determined by coaching a patient to perform a specified breathing maneuver, wherein the insulin cloud comprises a mixture of insulin and air.