PROCESS FOR TRANSIENT AND STEADY STATE DELIVERY OF BIOLOGICAL AGENTS TO THE LUNG VIA BREATHABLE LIQUIDS

• US 20110162646A1
• Filed: 03/17/2011
• Published: 07/07/2011
• 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 8,375,943 B2
• Time in Patent Office: Days
• US Class Current: 128/203.14
• 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 a biological agent in a breathable liquid to a lung of a patient via a liquid ventilation system comprising a ventilator circuit, the method comprising the steps 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.

2. The method according to claim 1, wherein ventilator circuit comprises a reservoir capable of holding the therapeutic mixture and a piping network capable of delivering the therapeutic mixture to the lung of the patient.

3. The method according to claim 1, wherein the mixing is performed by one or more of sonication, ultrasound, and vibration.

4. The 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.

5. The method according to claim 1, wherein the steady state ventilation comprises a tidal volume from about 10 to about 20 ml/kg.

6. The method according to claim 1, wherein the steady state ventilation comprises an inspiratory time from about 3 to about 7 seconds.

7. The method according to claim 1, wherein the steady state ventilation comprises an expiratory time from about 8 to about 15 seconds.

8. The method according to claim 1, wherein the steady state ventilation comprises an inspiratory:

expiratory timing ratio value from about 1;

2 to about 1;

3.

9. The method according to claim 1, wherein the steady state ventilation comprises a breathing rate from about 3 to about 8 breaths per minute.

10. The method according to claim 1, wherein the steady state ventilation comprises an inspiratory flow rate from about 200 to about 280 ml/sec/kg.

11. The method according to claim 1, wherein the steady state ventilation comprises an expiratory flow rate from about 20 to about 60 ml/sec/kg.

12. The method according to claim 1, wherein the steady state ventilation comprises an inspiratory alveolar pressure of about 10 cmH₂O.

13. The method according to claim 1, wherein the steady state ventilation comprises an expiratory alveolar pressure of about 3 cmH₂O.

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

15. The method according to claim 14, wherein the servo-control unit performs one or more of controlling flow of the therapeutic mixture, calculating the amount of biological agent that must be added to maintain a substantially stable concentration of the biological agent in the therapeutic mixture in the system, injecting the calculated amount of the biological agent into the system, and controlling the steady state ventilation.

16. The method according to claim 1, wherein the biological agent is introduced to the liquid ventilation system by injection.

17. The method according to claim 1, further comprising calculating the amount of biological agent that must be added to maintain the substantially stable concentration of the biological agent in the lung.

18. A servo-controlled method of delivering a biological agent in a breathable liquid to a lung of a patient via a liquid ventilation system comprising a ventilator circuit comprising a piping network, the method comprising the steps 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;

passing the therapeutic mixture through the piping network to fill the lung with the therapeutic mixture;

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

a tidal volume from about 10 to about 20 ml/kg,

an inspiratory time from about 3 to about 7 seconds,

an expiratory time from about 8 to about 15 seconds,

an inspiratory;

expiratory timing ratio value from about 1;

2 to about 1;

3,

a breathing rate from about 3 to about 8 breaths per minute,

an inspiratory flow rate from about 200 to about 280 ml/sec/kg, and

an expiratory flow rate from about 20 to about 60 ml/sec/kg; and

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

19. The method according to claim 18, 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.