Process for transient and steady state delivery of biological agents to the lung via breathable liquids

• US 20060278224A1
• Filed: 06/09/2005
• Published: 12/14/2006
• Est. Priority Date: 06/09/2005
• Status: Active Grant

• Current Assignee: Temple University of The Commonwealth System of Higher Education
• Original Assignee: Temple University of The Commonwealth System of Higher Education
• Inventors: Wolfson, Marla R., Shaffer, Thomas H.
• Granted Patent: US 7,909,031 B2
• Time in Patent Office: Days
• US Class Current: 128/204.260
• CPC Class Codes: A61M 16/0054 Liquid ventilation
• CPC Class Codes: A61M 16/22 Carbon dioxide-absorbing devices ; Other means for removing carbon dioxidecartridges with absorbing substances for respiratory apparatus A62B19/00
• CPC Class Codes: A61M 2202/0476 Oxygenated solutions

Abstract

The present invention includes a transient method of delivering a biological agent in a breathable liquid to a lung of a patient. The present invention includes a steady state method of delivering a biological agent in a breathable liquid to a lung of a patient. The steps of both the transient delivery method and the steady state delivery method can be controlled by a servo-control unit. A supplementary biological agent delivery step can be performed in both the transient method of delivering a biological agent and the steady state method of delivering a biological agent.

Claims

1. A method of delivering via a delivery system a biological agent in a breathable liquid to a lung of a patient, the method comprising the following steps:

establishing the patient'"'"'s baseline ventilation pattern, the baseline ventilation pattern comprising a baseline lung volume, a baseline tidal volume, and a baseline inspiratory time of the baseline tidal volume;

increasing the patient'"'"'s lung volume above the baseline lung volume;

allowing the lung to reach at or about mid-tidal volume in a breath;

introducing the biological agent to the delivery system when the lung is at or about mid-tidal volume;

increasing the lung tidal volume above the baseline tidal volume of the lung;

increasing inspiratory time of the tidal volume above the baseline inspiratory time of the baseline tidal volume; and

returning the lung of the patient to the baseline ventilation pattern.

2. A method according to claim 1, wherein the patient'"'"'s lung volume is increased no more than about 33% above the baseline lung volume.

3. A method according to claim 2, wherein the patient'"'"'s lung volume is increased from about 5% to about 30% above the baseline lung volume.

4. A method according to claim 3, wherein the patient'"'"'s lung volume is increased to about 25% above the baseline lung volume.

5. A method according to claim 1, wherein the patient'"'"'s lung volume is increased in a step-wise manner.

6. A method according to claim 1, wherein the biological agent is introduced to the delivery system by injection.

7. A method according to claim 1, wherein the biological agent is introduced to the delivery system at about minus 10% to about plus 10% of the mid tidal volume.

8. A method according to claim 7, wherein the biological agent is introduced to the delivery system at about minus 5% to about plus 5% of mid tidal volume.

9. A method according to claim 1, wherein the increased tidal volume of the lung is no more than about 20% greater than the baseline tidal volume of the lung.

10. A method according to claim 1, wherein the increased inspiratory time is no more than about 66% longer than the baseline inspiratory time.

11. A method according to claim 1, wherein the increased tidal volume and the increased inspiratory time is maintained for about 1 to about 15 breaths of the patient.

12. A method according to claim 11, wherein the increased tidal volume and the increased inspiratory time is maintained for about 5 to about 10 breaths of the patient.

13. A method according to claim 1, wherein the method further comprises:

measuring a loss rate, the loss rate comprising a rate at which the biological agent is metabolized by the patient; and

adding a supplementary amount of the biological agent to the delivery system at a rate substantially equivalent to the loss rate.

14. A method according to claim 1, wherein a servo-control unit controls timing of the steps of the method.

15. A method according to claim 1, wherein the biological agent is selected from the group consisting of an antibody-linked radionuclide, a vasoconstrictor, a vasodilator, a bronchoconstrictor, a bronchodilator, an anti-cancer agent, a surfactant, a steroid, an antibiotic agent, a chemotactic agent, a chemotherapeutic agent, a contrast agent, an antioxidant and an antiprotease, or a combination thereof.

16. A method of delivering via a delivery system a biological agent in a breathable liquid to a lung of a patient the method comprising the step of:

mixing the biological agent with a breathable liquid substantially equal in volume to an initial filling volume of the lung to create a substantially homogeneous therapeutic mixture;

filling the lung with the therapeutic mixture;

establishing a steady state ventilation that circulates the therapeutic mixture in the lung and the ventilator circuit; and

adding additional biological agent to the ventilator circuit to maintain a substantially stable concentration of the biological agent in the lung.

17. A method according to claim 16, wherein the steps of the method are controlled by a servo-control unit.

18. A method according to claim 16, wherein the biological agent is selected from the group consisting of an antibody-linked radionuclide, a vasoconstrictor, a vasodilator, a bronchoconstrictor, a bronchodilator, an anti-cancer agent, a surfactant, a steroid, an antibiotic agent, a chemotactic agent, a chemotherapeutic agent, a contrast agent, an antioxidant and an antiprotease, or a combination thereof.