Liquid aerosol formulations containing insulin and aerosol generating devices and methods for generating aerosolized insulin

• US 7,683,029 B2
• Filed: 04/23/2004
• Issued: 03/23/2010
• Est. Priority Date: 05/07/2003
• Status: Active Grant

• Current Assignee: Philip Morris USA Incorporated (Altria Group, Inc.)
• Original Assignee: Philip Morris USA Incorporated (Altria Group, Inc.)
• Inventors: Hindle, Michael, Cox, Kenneth A.
• Primary Examiner(s): Haghighatian; Mina
• Assistant Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US10/829,945
• Publication Number:
  US 20040223917A1
• Time in Patent Office: 2,160 Days
• Field of Search: 514/3, 128/203.12, 128/203.26
• US Class Current: 514/5.9
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61M 11/007 Syringe-type or piston-type sprayers or atomisers
• CPC Class Codes: A61M 11/041 using heaters
• CPC Class Codes: A61M 11/042 electrical
• 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 15/008 Electronic counters
• CPC Class Codes: A61M 15/02 with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
• CPC Class Codes: A61M 15/025 Bubble jet droplet ejection devices
• CPC Class Codes: A61M 2016/0039 in the inspiratory circuit
• CPC Class Codes: A61M 2205/8206 battery-operated
• CPC Class Codes: A61M 2205/8237 Charging means
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

Liquid aerosol formulations for generating aerosolized insulin include insulin and at least one high volatility carrier which protects the insulin from thermal degradation during vaporization of the carrier. The carrier can be a mixture of ethanol and water and the liquid aerosol formulation can be propellant free. An aerosol generating device generates the aerosolized insulin by passing the liquid aerosol formulation through a flow passage heated to convert the liquid into a vapor which entrains insulin particles which mix with air to form an aerosol. The insulin particles can be dry insulin particles produced by a hand held inhaler. By controlling the concentration of the insulin in the formulation, the size of the flow passage and/or the amount of heat which heats the flow passage, the aerosol can be provided with a selected mass median aerodynamic diameter of 1 to 3 μm or less than 1 μm so as to be delivered to a targeted portion of the lung using the inhaler.

Claims

1. An aerosol generating device, comprising:

a liquid source of a liquid aerosol formulation comprising a high volatility carrier and insulin;

a flow passage in fluid communication with the liquid source wherein the flow passage has an outlet which opens into ambient air;

a heater disposed to heat the liquid aerosol formulation in a heated portion of the flow passage to 100 to 150°

C. to produce a vapor which exits the flow passage outlet and admixes with ambient air to produce a dry powder aerosol;

a power supply; and

a controller operable to deliver a dose of the liquid aerosol formulation to the flow passage and control power from the power supply to the heater so as to maintain the heater at a temperature range of 100 to 150°

C. effective to vaporize the liquid aerosol formulation in the flow passage and produce an emitted dose of the dry powder aerosol in ambient air,

wherein the aerosol generator is operable to achieve a respirable fraction of at least 70% of the emitted dose.

2. The aerosol generating device of claim 1, wherein the carrier is ethanol.

3. The aerosol generating device of claim 1, wherein the insulin is human insulin.

4. The aerosol generating device of claim 3, wherein the carrier is an ethanol and water mixture.

5. The aerosol generating device of claim 4, wherein the water comprises at least 20 volume %.

6. The aerosol generating device of claim 1, wherein the insulin is dissolved in the carrier.

7. The aerosol generating device of claim 1, wherein the liquid aerosol formulation is propellant free.

8. The aerosol generating device of claim 1, wherein the aerosol generator is operable to produce the dry powder aerosol comprising aerosol particles that consist essentially of the insulin.

9. The aerosol generating device of claim 1, wherein the aerosol generator is operable to produce the dry powder aerosol with a mass median aerodynamic diameter in a range between 0.1 and 0.9 μ

m.

10. The aerosol generating device of claim 9, further comprising at least one valve disposed between the liquid source and the flow passage, the controller is operable to actuate the valve to open and close the flow passage to control flow of the liquid aerosol formulation from the liquid source to the flow passage.

11. The aerosol generating device of claim 9, further comprising:

a mouthpiece through which the aerosol is inhaled by a user of the aerosol generating device;

a pressure sensor;

an air passage through which air is supplied into the mouthpiece; and

a valve which opens and closes the air passage;

wherein the controller is operable to actuate the valve within a predetermined time period after the pressure sensor detects a pressure drop in the mouthpiece as the user inhales on the mouthpiece to allow air to be supplied into the mouthpiece.

12. The aerosol generating device of claim 1, wherein the flow passage comprises a metering chamber having a predetermined volume, and the aerosol generating device comprises a discharge member operable to deliver an amount of the liquid aerosol formulation equal to the predetermined volume into the heated portion of the flow passage.

13. The aerosol generating device of claim 1, which is a hand held inhaler.

14. The aerosol generating device of claim 1, wherein the liquid source is removably attached to the aerosol generating device.

15. The aerosol generating device of claim 1, wherein the aerosol generator is operable to produce dry powder aerosol particles of insulin entrained in a vapor, wherein the dry powder aerosol particles consist essentially of insulin and the vapor is propellant free and the dry powder aerosol has a mass median aerodynamic diameter of 0.01 to 1 μ

m or 1 to 3 μ

m.

16. The aerosol generating device of claim 1, wherein the flow passage has a maximum transverse dimension of 0.001 to 0.05 mm, 0.05 to 0.5 mm, or 0.5 to 10 mm.

17. An aerosol generating device, comprising:

a liquid source of a liquid aerosol formulation comprising a carrier and insulin;

a flow passage in fluid communication with the liquid source wherein the flow passage has an outlet which opens into ambient air;

a heater disposed to heat the liquid aerosol formulation in a heated portion of the flow passage to 100 to 150°

C. to produce a vapor which exits the flow passage outlet and admixes with ambient air to produce a dry powder aerosol;

a power supply; and

a controller operable to deliver a dose of the liquid aerosol formulation to the flow passage and control power from the power supply to the heater so as to maintain the heater at a temperature range of 100 to 150°

C. effective to vaporize the liquid aerosol formulation in the flow passage and produce an emitted dose of the dry powder aerosol in ambient air,

wherein the aerosol generator is operable to achieve a respirable fraction of at least 70% of the emitted dose.

18. The aerosol generating device of claim 17, wherein the aerosol generator is operable to produce dry powder aerosol particles of insulin entrained in a vapor, wherein the dry powder aerosol particles consist essentially of insulin and the vapor is propellant free and the dry powder aerosol has a mass median aerodynamic diameter of 0.01 to 1 μ

m or 1 to 3 μ

m.

19. The aerosol generating device of claim 17, wherein the flow passage has a maximum transverse dimension of 0.001 to 0.05 mm, 0.05 to 0.5 mm, or 0.5 to 10 mm.