Method of treating diabetes mellitus in a patient

• US 20020124852A1
• Filed: 05/03/2001
• Published: 09/12/2002
• Est. Priority Date: 01/29/1993
• Status: Abandoned Application

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Farr, Stephen J., Gonda, Igor, Rubsamen, Reid M.
• Application Number:
  US09/848,774
• Publication Number:
  US 20020124852A1
• Time in Patent Office: Days
• US Class Current: 128/898
• 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

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

32. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) supplying a predetermined amount of 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) 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; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein an amount of said insulin in said cloud effective, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient is absorbed into the bloodstream of said patient.

33. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) supplying a predetermined amount of 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) contacting said insulin with a compressed gas to form a cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled 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; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein an amount of insulin in said cloud effective, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient is absorbed into the bloodstream of said patient.

34. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) mechanically supplying a predetermined amount of insulin to a given area of 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) aerosolizing said insulin with a compressed gas to form a cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled 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; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein an amount of insulin in said cloud effective, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient is absorbed into the bloodstream of said patient.

35. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) supplying a predetermined amount of insulin in the form of a dry powder 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) contacting said insulin with a compressed gas to form a cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled 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; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein an amount of insulin in said cloud effective, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient is absorbed into the bloodstream of said patient.

36. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) mechanically supplying a predetermined amount of insulin in the form of a dry powder to a given area of 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) aerosolizing said insulin with a compressed gas to form a cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled 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; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein an amount of insulin in said cloud effective, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient is absorbed into the bloodstream of said patient.

37. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) supplying a predetermined amount of insulin in the form of a dry powder to a hand held device, said predetermined amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in the blood of said patient;

(b) contacting said insulin with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in the blood of said patient; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein an amount of insulin in said cloud effective, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient is absorbed into the bloodstream of said patient.

38. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) mechanically supplying a predetermined amount of insulin in the form of a dry powder to a given area of a hand held device, said predetermined amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient;

(b) aerosolizing said insulin with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in the blood of said patient; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein an amount of insulin in said cloud effective, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient is absorbed into the bloodstream of said patient.

39. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) supplying a predetermined amount of insulin in the form of a dry powder to a hand held device, said predetermined amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient;

(b) contacting said insulin with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in the blood of said patient; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein 1 to 30 units of insulin are absorbed into the bloodstream of said patient.

40. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) mechanically supplying a predetermined amount of insulin in the form of a dry powder to a given area of a hand held device, said predetermined amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient;

(b) aerosolizing said insulin with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in the blood of said patient; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said insulin cloud to the lungs of said patient, wherein 1 to 30 units of insulin are absorbed into the bloodstream of said patient.

41. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) supplying a predetermined amount of insulin in the form of a dry powder to a hand held device, said predetermined amount being 2 to 300 units of insulin;

(b) contacting said insulin with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 300 units of insulin; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient;

wherein 1 to 30 units of insulin are repeatably absorbed into the bloodstream of said patient.

42. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) mechanically supplying a predetermined amount of insulin in the form of a dry powder to a given area of a hand held device, said predetermined amount being 2 to 300 units of insulin;

(b) aerosolizing said insulin with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 300 units of insulin; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient;

wherein 1 to 30 units of insulin are repeatably absorbed into the bloodstream of said patient.

43. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) determining the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level;

(b) aerosolizing, in a hand held device, a predetermined amount of insulin in excess of said required amount of insulin with a compressed gas to form a cloud in said hand held device, said cloud comprising a repeatable amount of insulin in excess of said required amount of insulin; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said insulin cloud to the lungs of said patient, wherein said required amount of insulin is absorbed into the bloodstream of said patient.

44. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) determining the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable blood glucose level;

(b) aerosolizing, in a hand held device, a predetermined amount of insulin in excess of said required amount of insulin with a compressed gas to form a cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin in excess of said required amount of insulin; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein said required amount of insulin is absorbed into the bloodstream of said patient.

45. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) determining the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level;

(b) aerosolizing, in a hand held device, a predetermined amount of insulin 2 to 10 times said required amount of insulin with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 10 times said required amount of insulin; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein said required amount of insulin is absorbed into the bloodstream of said patient.

46. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) determining the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level, said required amount being 1-30 units;

(b) aerosolizing, in a hand held device, a predetermined amount of a dry powder comprising insulin, said predetermined amount being 2 to 10 times said required amount of insulin, with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being 2 to 10 times said required amount of insulin; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said cloud to the lungs of said patient, wherein from 1 to 30 units of insulin are absorbed into the bloodstream of said patient.

47. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) determining the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level, said required amount being from 1-30 units;

(b) aerosolizing, in said hand held device, a predetermined amount of insulin in the form of a dry powder, said predetermined amount being from 2 to 300 units of insulin, with a compressed gas to form a dry cloud in said hand held device, said cloud comprising a repeatable and controlled amount of insulin, said repeatable and controlled amount being from 2 to 300 units of insulin; and

(c) inhaling said cloud at an inspiratory flow rate and volume adapted to deliver a portion of said insulin cloud to the lungs of said patient;

wherein from 1 to 30 units of insulin are repeatably absorbed into the bloodstream of said patient.

48. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) aerosolizing, in a hand held device, a first predetermined amount of insulin, which is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level, with a compressed gas to form a first cloud in said hand held device, said first cloud comprising a first repeatable and controlled amount of insulin which is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level;

(b) inhaling said first cloud at an inspiratory flow rate and volume adapted to deliver a portion of said first cloud to the lungs of said patient, wherein insulin is absorbed into the bloodstream of said patient; and

(c) repeating (a) and (b) with a second predetermined amount of insulin which is the same as or different from said first predetermined amount and is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level and a second repeatable and controlled amount of insulin which is the same as or different from said first repeatable and controlled amount and is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level.

49. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) aerosolizing, in a hand held device, a first predetermined amount of insulin in the form of a dry powder with a compressed gas to form a first cloud in said hand held device, said first predetermined amount being an amount in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level, said first cloud comprising a first repeatable and controlled amount of insulin which is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level;

(b) inhaling said first cloud at an inspiratory flow rate and volume adapted to deliver a portion of said first cloud to the lungs of said patient, wherein insulin is absorbed into the bloodstream of said patient; and

(c) repeating (a) and (b) with a second predetermined amount of insulin which is the same as or different from said first predetermined amount and is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level and a second repeatable and controlled amount of insulin which is the same as or different from said first repeatable and controlled amount and is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level.

50. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) aerosolizing, in a hand held device, a first predetermined amount of insulin in the form of a dry powder, said first predetermined amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient, with a compressed gas to form a first dry cloud in said hand held device, said first cloud comprising a first repeatable and controlled amount of insulin which is 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient;

(b) inhaling said first cloud at an inspiratory flow rate and volume adapted to deliver a portion of said first cloud to the lungs of said patient, wherein insulin is absorbed into the bloodstream of said patient;

(c) repeating (a) and (b) with a second predetermined amount of insulin which is the same as or different from said first predetermined amount and is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level and a second repeatable and controlled amount of insulin which is the same as or different from said first repeatable and controlled amount and is in excess of the amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level.

51. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) aerosolizing, in a hand held device, a first predetermined amount of insulin in the form of a dry powder, said first predetermined amount being 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient, with a compressed gas to form a first dry cloud in said hand held device, said first cloud comprising a first repeatable and controlled amount of insulin which is 2 to 10 times that amount required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level in said patient;

(b) inhaling said first cloud at an inspiratory flow rate and volume adapted to deliver a portion of said first cloud to the lungs of said patient, wherein 1 to 30 units of insulin are absorbed into the bloodstream of said patient;

(c) repeating (a) and (b) with a second predetermined amount of insulin which is the same as or different from said first predetermined amount and is 2 to 10 times that amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level and a second repeatable and controlled amount of insulin which is the same as or different from said first repeatable and controlled amount and is 2 to 10 times that amount of insulin required, in the bloodstream of said patient, to produce or maintain an acceptable serum glucose level.

52. A method of treating diabetes mellitus in a patient in need thereof, said method comprising:

(a) aerosolizing, in a hand held device, a first predetermined amount of insulin in the form of a dry powder, said first predetermined amount being 2 to 300 units of insulin, with a compressed gas to form a first dry cloud in said hand held device, said first cloud comprising a first repeatable and controlled amount of insulin being 2 to 300 units of insulin;

(b) inhaling said first cloud at an inspiratory flow rate and volume adapted to deliver a portion of said first cloud to the lungs of said patient;

wherein from 1 to 30 units of insulin are repeatably absorbed into the bloodstream of said patient;

(c) repeating (a) and (b) with a second predetermined amount which is the same as or different from said first predetermined amount and is 2 to 300 units of insulin and a second repeatable and controlled amount which is the same as or different from said first repeatable and controlled amount and is 2 to 300 units of insulin.