Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume

• US 7,028,686 B2
• Filed: 11/04/2003
• Issued: 04/18/2006
• 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): Lewis, Aaron J.
• Application Number:
  US10/701,967
• Publication Number:
  US 20040089290A1
• Time in Patent Office: 896 Days
• Field of Search: 128/200.14, 128/200.22, 128/200.23, 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 15/0043 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 15/0085 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
• CPC Class Codes: B05B 17/0607 : generated by electrical means, e.g. piezoelectric transducers

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 administering a formulation to a human patient by inhalation, comprising:

(a) aerosolizing a formulation comprised of a pharmaceutically active compound wherein the aerosol is comprised of particles having a diameter in a range of about 0.5 to 6.0 microns;

(b) inhaling the aerosolized formulation with a known volume of air,

(c) repeating (a) and (b) a plurality of times over a period of time;

wherein the known volume of air with aerosolized formulation inhaled in each step (b) is substantially the same for each step (b) and further wherein the inhaled volume of air in step (b) is determined by the patient inhaling maximally which inhaling maximally is repeated for each step (b).

2. The method of claim 1 wherein said period of time is daily.

3. The method of claim 1 wherein said period of time is weekly.

4. The method of claim 1 wherein said repeating in step (c) is at meal times.

5. The method of claim 1, further comprising:

(d) measuring the patient'"'"'s inspiratory flow rate during the inhaling step (b);

wherein aerosolizing in step (a) is repeated in step (c) at substantially a same measured inspiratory flow rate and substantially a same measured inspiratory volume.

6. The method of claim 1, wherein the formulation is aerosolized in step (a) by moving the formulation through a porous membrane having pores with a diameter in the range of about 0.5 to 3.0 microns.

7. The method of claim 1, wherein the aerosolizing of step (a) is repeated in step (c) within a range of about 0.1 to about 2.0 liters/second and within a range of about 0.15 to about 0.80 liters.

8. The method of claim 1, wherein the inhaling of step (b) is continued after inhaling the aerosolized formulation with a known volume of air.

9. The method of claim 8, wherein a total inhaled volume is in the range of about 75% to about 100% of the patient'"'"'s total lung volume minus residual lung volume.

10. The method of claim 9, wherein the formulation is chosen from a liquid flowable formulation and a substantially dry formulation.

11. The method of claim 10, wherein the aerosol comprises particles that have a diameter in a range of from about 0.5 to about 3 microns.

12. The method of claim 1, wherein the active compound is in a carrier in a concentration in a range of from about 0.01% to about 12.5%.

13. The method of claim 12, wherein the formulation is a liquid.

14. The method of claim 12, wherein the formulation is a dry powder.

15. The method of claim 1, wherein the inhaling of step (b) is preceded by the patient exhaling.

16. The method of claim 15, wherein the exhaling comprises exhaling a determined volume of air.

17. The method of claim 16, wherein the exhaled volume is determined by coaching a patient to exhale maximally.

18. The method of claim 1, wherein the aerosolizing is carried out by a metered dose inhaler.

19. The method as claimed in claim 1, wherein the pharmaceutically active compound is an insulin analog.

20. The method as claimed in claim 1, wherein the pharmaceutically active compound is insulin.

21. The method as claimed in claim 20, further comprising:

orally administering a sulfonylurea.

22. The method as claimed in claim 21, wherein the sulfonylurea is chlorpropamide.

23. The method as claimed in claim 21, wherein the sulfonylurea is tolazamide.

25. The method as claimed in claim 21, wherein the sulfonylurea is glipzide.

26. The method as claimed in claim 21, wherein the sulfonylurea is glyburide.

27. The method as claimed in claim 1, wherein the formulation is a liquid formulation and an amount in the range of 10 ul to 10 ml is aerosolized.

28. The method as claimed in claim 27, wherein the amount of formulation aerosolized is in a range of about 50 ul to about 1,000 ul.

24. The method as claimed in 21, wherein the sulfonylurea is tolbutamide.

29. A method of administering a formulation to a human patient by inhalation, comprising:

aerosolizing a formulation comprises of a pharmaceutically active compound wherein the aerosol is comprised of particles having a diameter in a range of about 0.5 to 6.0 microns;

(b) inhaling the aerosolized formulation with a known volume of air, and

(c) repeating (a) and (b) a plurality of times over a period of time;

wherein the known volume of air with aerosolized tion inhaled in each step (b) is substantially the same for each step (b) wherein the inhaling of step (b) is continued after inhaling the aerosolized formulation with a known volume of air and wherein a total inhaled volume is in a range of 75% to about 100% of the patient'"'"'s total lung volume minus residual lung volume.

30. The method of claim 29 wherein said period of time daily.

31. The method of claim 29 wherein said period of tine is weekly.

32. The method of claim 29 wherein repeating step (c) is at meal times.

33. The method of claim 29, wherein the inhaled volume of air in step (b) is determined by the patient inhaling maximally which inhaling maximally is repeated for each step (b).

34. The method of claim 29, further comprising:

(d) measuring the patient'"'"'s inspiratory flow rate during the inhaling step (b);

wherein aerosolizing in step (a) is repeated in step (c) at substantially a same measured inspiratory flow rate and substantially a same measured inspiratory volume.

35. The method of claim 29, wherein the formulation is aerosolized in step (a) by moving the formulation through a porous membrane having pores with a diameter in the range of about 0.5 to 3.0 microns.

36. The method of claim 29, wherein the aerosolizing of step (a) is repeated in step (c) within a range of about 0.1 to about 2.0 liters/second and within a range of about 0.15 to about 0.80 liters.

37. The method of claim 29, wherein the formulation is chosen from a liquid flowable formulation and a substantially dry formulation.

38. The method of claim 29, wherein the aerosol comprises particles that have a diameter in a range of from about 0.5 to about 3 microns.

39. The method of claim 29, wherein the active compound is in a carrier in a concentration in a range of from about 0.01% to about 12.5%.

40. The method of claim 39, wherein the formulation is a liquid.

41. The method of claim 39, wherein the formulation is a dry powder.

42. The method of claim 29, wherein the inhaling of step (b) is preceded by the patient exhaling.

43. The method of claim 42, wherein the exhaling comprises exhaling a determined volume of air.

44. The method of claim 43, wherein the exhaled volume is determined by coaching a patient to exhale maximally.

45. The method of claim 29, wherein the aerosolizing is carried out by a metered dose inhaler.

46. The method as claimed in claim 29, wherein the pharmaceutically active compound is an insulin analog.

47. The method as claimed in claim 29, wherein the pharmaceutically active compound is insulin.

48. The method as claimed in claim 47, further comprising:

orally administering a sulfonylurea.

49. The method as claimed in claim 48, wherein the sulfonylurea is chlorpropamide.

50. The method as claimed in claim 48, wherein the sulfonylurea is tolazamide.

51. The method as claimed in claim 48, wherein the sulfonylurea is tolbutamide.

52. The method as claimed in claim 48, wherein the sulfonylurea is glipzide.

53. The method as claimed in claim 48, wherein the sulfonylurea is glyburide.

54. The method as claimed in claim 29, wherein the formulation is a liquid formulation and an amount in the range of 10 ul to 10 ml is aerosolized.

55. The method as claimed in claim 54, wherein the amount of formulation aerosolized is in a range of about 50 ul to about 1,000 ul.