Method and composition for the treatment of lung surfactant deficiency or dysfunction

• US 20050229926A1
• Filed: 03/14/2005
• Published: 10/20/2005
• Est. Priority Date: 04/20/2004
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Aerogen, Inc. (Nektar Therapeutics)
• Inventors: Fink, James, Ivri, Yehuda
• Granted Patent: US 7,201,167 B2
• Time in Patent Office: Days
• US Class Current: 128/200.160
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 16/0666 Nasal cannulas or tubing devices for improving normal breathing through the nose A61F5/08; nose filters A62B23/06; outside holding devices A61M25/02
• CPC Class Codes: A61M 16/08 Bellows; Connecting tubes having means for taking samples G01N1/22; Water traps; Patient circuits
• CPC Class Codes: A61M 16/0833 T- or Y-type connectors, e.g. Y-piece
• CPC Class Codes: A61M 16/1055 bacterial
• CPC Class Codes: A61M 16/1065 in the expiratory path
• CPC Class Codes: A61M 16/14 by mixing different fluids, one of them being in a liquid phase
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2016/0033 electrical
• CPC Class Codes: A61M 2205/7518 bacterial

Abstract

A method of treating a disease involving surfactant deficiency or dysfunction in a patient'"'"'s lungs is disclosed comprising the steps of providing a liquid lung surfactant composition; aerosolizing the lung surfactant composition with a vibrating aperture-type aerosol generator to form a surfactant aerosol; and introducing the surfactant aerosol into the gas flow within a circuit of a pressure-assisted breathing system coupled to the patient'"'"'s respiratory system, whereby a therapeutically effective amount of said surfactant is delivered to the patient'"'"'s lungs. Apparatus is also disclosed that increases the efficiency of delivery of aerosolized medicaments such as aerosolized lung surfactant.

Claims

1. A method of treating a disease involving surfactant deficiency or dysfunction in a patient'"'"'s lungs, comprising the steps of:

providing a liquid lung surfactant composition;

aerosolizing the lung surfactant composition with a vibrating aperture-type aerosol generator to form a surfactant aerosol; and

introducing the surfactant aerosol into the gas flow within a circuit of a pressure-assisted breathing system coupled to the patient'"'"'s respiratory system, whereby a therapeutically effective amount of said lung surfactant is delivered to the patient'"'"'s lungs.

2. A method according to claim 1 wherein the lung surfactant is a natural surfactant derived from animal lungs or a synthetically engineered lung surfactant.

3. A method according to claim 1 wherein the liquid lung surfactant composition has a concentration of from 20-120 mg/ml.

4. A method according to claim 1 wherein 10-80% of the active lung surfactant is inhaled by the patient.

5. A method according to claim 4 wherein 5-50% of the active lung surfactant is delivered to the patient'"'"'s lungs.

6. A method according to claim 1 wherein said therapeutically effective amount of lung surfactant is in the range of 2-400 mg.

7. A method according to claim 6 wherein the delivery rate of lung surfactant to the patient'"'"'s lungs is in the range of 2-800 mg/hr .

8. A method according to claim 1 wherein the aerosol output of the vibrating aperture-type aerosol generator is in the range of 0.1-0.5 ml/min.

9. A method according to claim 1 wherein said pressure-assisted breathing system is a CPAP system.

10. A method according to claim 1 wherein the particle size of the lung surfactant aerosol is less than 5 μ

m MMAD.

11. In a surfactant replacement therapy wherein a liquid lung surfactant composition is aerosolized and delivered to the lungs of a patient having lung surfactant deficiency or dysfunction, the improvement which comprises:

aerosolizing the lung surfactant with a vibrating aperture-type aerosol generator; and

introducing the aerosolized lung surfactant into the gas flow within a circuit of a pressure-assisted breathing system coupled to the patient'"'"'s respiratory system.

12. A surfactant replacement therapy according to claim 11 wherein the circuit of the pressure-assisted breathing system provides a straight or gently angled path for the flow of aerosol particles from the point at which the aerosol generator introduces the aerosolized lung surfactant into the gas flow to the point at which the aerosolized lung surfactant enters the patient'"'"'s respiratory system.

13. A surfactant replacement therapy according to claim 11 wherein the pressure-assisted breathing system is a CPAP system.

14. A surfactant replacement therapy according to claim 13 wherein the aerosolized lung surfactant is introduced into the respiratory circuit of the CPAP system.

15. A surfactant replacement therapy according to claim 14 wherein a higher concentration of aerosolized lung surfactant than generated by the aerosol generator is first collected in a plenum chamber located outside the respiratory circuit, and then discharged into the respiratory circuit.

16. A surfactant replacement therapy according to claim 15 wherein the plenum chamber has an internal volume of 5-400 ml.

17. A surfactant replacement therapy according to claim 15 wherein the mass of surfactant inhaled by the patient is at least 80% of the surfactant provided to the aerosol generator.

18. A surfactant replacement therapy according to claim 17 wherein the inhaled mass is provided in at least 25% of the time required for a breath actuated nebulizer to provide the same inhaled mass

19. A surfactant replacement therapy according to claim 13 wherein the CPAP system comprises means for discontinuing the introduction of aerosolized lung surfactant into the gas flow when the patient exhales.

20. A surfactant replacement therapy according to claim 11 wherein the rebreathed volume is no more than 5 ml.

21. Apparatus for the delivery of an aerosolized medicament to a patient comprising:

a pressure-generating circuit having a first gas flow that maintains a positive pressure within the apparatus;

a patient interface device coupled to a patient'"'"'s respiratory system;

a respiratory circuit for providing gas communication between the pressure-generating circuit and the patient'"'"'s respiratory system, wherein the gas flow in the respiratory circuit is lower volume than the first gas flow;

a plenum chamber located outside of and in gas communication with the respiratory circuit;

a vibrating aperture-type aerosol generator positioned so as to generate aerosolized medicament into the plenum chamber, wherein a concentration of aerosolized medicament is collected in the plenum chamber that is higher than the concentration generated by the aerosol generator;

a conduit from the plenum chamber to a point in the respiratory circuit proximal to the patient'"'"'s airway; and

means for introducing a controlled secondary gas flow into the plenum chamber to drive concentrated aerosolized medicament through the conduit into the gas flow in the respiratory circuit.

22. Apparatus according to claim 21 wherein the plenum chamber has an internal volume of 5-400 ml.

23. Apparatus according to claim 21 wherein the plume of aerosolized medicament generated by the aerosol generator does not impact the bottom or walls of the plenum chamber.

24. Apparatus according to claim 21 wherein the conduit has a one-way valve or conduit that controls the flow of concentrated aerosolized medicament to the respiratory circuit so as to isolate the volume of gas in the plenum chamber from being rebreathed volume.

25. Apparatus according to claim 21 wherein the aerosolized medicament is a lung surfactant.