Method Of Treating Diabetes Mellitus In A Patient

• US 20080060644A1
• Filed: 10/05/2007
• Published: 03/13/2008
• Est. Priority Date: 01/29/1993
• Status: Active Application

• Current Assignee: Aradigm Corporation
• Original Assignee: NOVO Nordisk A/S - NOVO ALLE
• Inventors: Rubsamen, Reid, Farr, Stephen, Gonda, Igor
• Application Number:
  US11/867,825
• Publication Number:
  US 20080060644A1
• Time in Patent Office: Days
• US Class Current: 128/203.12
• 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 human insulin or monomeric or analog insulin. When delivering insulin (not monomeric) by inhalation, the total inhaled volume should be about the same at each delivery to obtain repeatable results, preferably a high volume is used, but a consistent low volume can be used as well. 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

1-25. -25. (canceled)

26. 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, 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 air to form an aerosolized suspension comprising a repeatable amount of insulin, said aerosolized suspension comprising insulin particles in the range between 0.5 and 6 microns; and

(d) inhaling said aerosolized suspension at an inspiratory flow rate in the range of 0.1 to 2.0 liters per second and wherein the inhaling of said aerosolized suspension occurs with a high volume V_h 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 glucose level is produced by systemically absorbing a controlled dose of insulin that comprises a percentage of the supplied amount of powdered insulin that was supplied to the device.

27. The method of claim 26, wherein the inhalation in the inhaling step is performed by making a maximal effort to inhale.

28. The method of claim 26, wherein the aerosol is comprised of human insulin particles between about 1 and 4 microns and occurs with a pressure less than 400 psi.

29. The method of claim 26 wherein the aerosolized suspension comprises human insulin particles having a size in the range of about 1-3 microns.

30. The method of claim 26, further comprising repeating steps a-e, wherein in each repetition of steps a-e, the patient inhales substantially the same volume V_h for each repetition.

31. The method of claim 30, wherein the inhaling occurs at substantially the same flow rate.

45. The method of claim 26, further comprising the step of performing a breath hold for a predetermined period of time immediately after the inhaling step.

48. The method of claim 26, wherein the insulin is human insulin.

32. 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 an aerosol 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 aerosol comprising insulin particles in the range between 0.5 and 6 microns;

exhaling a determined volume of air;

inhaling said aerosol of insulin at an inspiratory flow rate in the range of 0.1 to 2.0 liters per second and wherein the inhaling of said aerosol 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.

33. The method of claim 32, wherein the insulin aerosol 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 aerosol 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.

46. The method of claim 32, further comprising the step of performing a breath hold for a predetermined period of time immediately after the inhaling step.

49. The method of claim 32, wherein the insulin is human insulin.

34. 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 an aerosol comprised of human insulin particles and air;

exhaling a volume of air;

inhaling the aerosol of insulin, 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).

35. The method of claim 34, wherein the determined point is determined by making a maximal effort to inhale.

36. The method of claim 34, 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.

37. The method of claim 36, 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.

38. The method of claim 37, wherein the flow rate during inhalation is substantially the same for each repetition of the inhalation.

39. The method of claim 36, wherein the insulin aerosol is inhaled before the patient inhales 0.8 liters of air.

40. The method of claim 39, 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.

41. The method of claim 40, wherein the specific maneuver comprises inhaling with a maximal effort.

42. The method of claim 39, 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.

43. The method of claim 42, wherein the inhaling of the insulin aerosol 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.

44. The method of claim 43, 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 aerosol comprises a mixture of insulin and air.

47. The method of claim 34, further comprising the step of performing a breath hold for a predetermined period of time immediately after the inhaling step.

50. A method of treating diabetes in a patient that is in need of such treatment, the method comprising:

supplying a controlled dosage of insulin to the patients circulatory system via the patients respiratory system and causing the patient to absorb a controlled amount of the insulin that is sufficient to maintain an acceptable blood glucose level;

wherein the method further comprises coaching the patient by teaching the patient to inhale a total volume of air and powder insulin that is a low volume V_L, wherein the patient repeats the step of inhaling the total volume of air and powder insulin and wherein for each repetition, the patient inhales substantially the same total volume V_L.

51. The method of claim 50, wherein the insulin powder is aerolized before inhaling and wherein the aerosol is comprised of particles under 10 microns.