Method, composition, and system to control pH in pulmonary tissue of a subject

• US 20100081956A1
• Filed: 09/30/2008
• Published: 04/01/2010
• Est. Priority Date: 09/30/2008
• Status: Abandoned Application

• Current Assignee: Searete LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Ishikawa, Muriel Y., Wood, Lowell L. JR., Rivet, Dennis J., Hyde, Roderick A., Kare, Jordin T., Wood, Victoria Y.H.
• Application Number:
  US12/286,753
• Publication Number:
  US 20100081956A1
• Time in Patent Office: Days
• US Class Current: 600/532
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/0003 with means for dispensing more than one drug
• 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 2230/208 pH-value
• CPC Class Codes: A61P 31/12 Antivirals

Abstract

Methods, pharmaceutical compositions, and systems are provided which include a method for treating a pulmonary viral infectious disease in a subject. The method includes administering a pharmaceutical composition including at least one agent to a pulmonary tissue of the subject, wherein the pharmaceutical composition is administered as two or more distinct and non-overlapping particle size ranges configured to contact two or more levels of pulmonary tissue of the subject, wherein the at least one agent is configured to achieve a selected pH range in the two or more levels of pulmonary tissue of the subject.

Claims

1. A method for treating a pulmonary viral infectious disease in a subject comprising:

administering a pharmaceutical composition including at least one agent to a pulmonary tissue of the subject, wherein the pharmaceutical composition is administered as two or more distinct and non-overlapping particle size ranges configured to contact two or more levels of pulmonary tissue of the subject, wherein the at least one agent is configured to achieve a selected pH range in the two or more levels of pulmonary tissue of the subject.

2. The method of claim 1, wherein the pulmonary tissue includes epithelial tissue, mesenchymal tissue, or endothelial tissue.

3. The method of claim 1, wherein the levels of pulmonary tissue include oropharynx or nasopharynx tissue.

4. The method of claim 1, wherein the levels of pulmonary tissue include trachial tissue.

5. The method of claim 1, wherein the levels of pulmonary tissue include bronchial, bronchiole, alveolar duct, or alveoli tissue.

6. The method of claim 1, wherein the at least one agent includes at least one buffering agent.

7. The method of claim 1, wherein the at least one agent includes at least one basic agent.

8. The method of claim 1, wherein the at least one agent includes at least one acidic agent.

9. The method of claim 1, wherein the two or more distinct and non-overlapping particle size ranges include powders, micronized microparticles, nanoparticles, or liposomes.

10. The method of claim 1, wherein the two or more distinct and non-overlapping particle size ranges include an anion exchange particle or a cation exchange particle.

11. The method of claim 9, wherein the two or more distinct and non-overlapping particle size ranges have an average size less than about 10 μ

m.

12. The method of claim 9, wherein the two or more distinct and non-overlapping particle size ranges have an average size less than about 6 μ

m.

13. The method of claim 9, wherein the two or more distinct and non-overlapping particle size ranges have an average size less than about 4 μ

m.

14. The method of claim 9, wherein the two or more distinct and non-overlapping particle size ranges have an average size less than about 2 μ

m.

15. The method of claim 9, wherein the two or more distinct and non-overlapping particle size ranges include less than about 4 μ

m, less than about 3 μ

m, less than about 2 μ

m, less than about 1500 nm, less than about 1 μ

m, less than about 800 nm, less than about 700 nm, less than about 600 nm, less than about 500 nm, less than about 400 nm, less than about 300 nm, less than about 200 nm, less than about 100 nm, less than about 75 nm, or less than about 50 nm.

16. The method of claim 9, wherein the two or more distinct and non-overlapping particle size ranges include less than about 1900 nm, less than about 1800 nm, less than about 1700 nm, less than about 1600 nm, less than about 1500 nm, less than about 1400 nm, less than about 1300 mm, less than about 1200 nm, less than about 1100 nm, less than about 1000 nm, less than about 900 nm, less than about 800 nm, less than about 700 nm, less than about 600 nm, less than about 500 nm, less than about 400 nm, less than about 300 nm, less than about 250 nm, less than about 200 nm, less than about 100 nm, less than about 75 nm, or less than about 50 nm.

17. The method of claim 9, wherein at least about 70%, at least about 90%, or at least about 95% of the two or more distinct and non-overlapping particle size ranges have a particle size less than the average particle size.

18. The method of claim 9, wherein the micronized microparticle includes a pharmaceutical carrier include lactose, dextran, dextrose, or mannitol, or mixtures thereof.

19. The method of claim 1, wherein the pharmaceutical composition includes a first agent in first-sized particles configured to maintain a first pH range in a first level of pulmonary tissue of the subject, and a second agent in second-sized particles configured to maintain a second pH range in a second level of pulmonary tissue of the subject.

20. The method of claim 19, wherein the first-sized particles and the second-sized particles include the two or more particle size ranges of less than about 10 μ

m, less than about 6 μ

m, less than about 4 μ

m, or less than about 2 μ

m.

21. The method of claim 19, wherein the first agent includes a buffering agent to maintain the first pH range below approximately 7.0.

22. The method of claim 19, wherein the first agent is a buffering agent configured to maintain the first pH range from approximately 7.2 to approximately 7.6.

23. The method of claim 19, wherein the second agent is a buffering agent configured to maintain the second pH range from approximately 6.4 to approximately 7.4.

24. The method of claim 1, wherein the pharmaceutical composition is administered in response to a sensed environmental condition.

25. The method of claim 24, wherein the sensed environmental condition includes a potentially infectious environment.

26. The method of claim 2, further comprising administering the pharmaceutical composition orally or intranasally.

27. The method of claim 1, wherein the pharmaceutical composition is configured to provide a timed-release of the buffering agents.

28. The method of claim 1, wherein the pharmaceutical composition is configured to provide a slow-absorbing form of the buffering agents.

29. The method of claim 1, wherein the at least one buffering agent is linked to a viral homing entity.

30. The method of claim 29, wherein the viral homing entity binds to a surface molecule of the virus.

31. The method of claim 29, wherein the viral homing entity binds to a cell or tissue of the subject.

32. The method of claim 1, wherein the buffering agent includes phosphate buffer, citrate buffer, lactate buffer, pyruvate buffer, or an organic acid buffer.

33. The method of claim 1, wherein a sensor is configured to monitor a condition of the subject.

34. The method of claim 33, wherein the sensor is configured to monitor at least one of pH of the pulmonary tissue or pH of an exhalant.

35. The method of claim 33, wherein the sensor is configured to monitor at least one of humidity of an exhalant, temperature, breathing rate, peak rate of exhalation, tidal volume, vital capacity, inspiratory capacity, expiratory reserve volume, or residual volume.

36. The method of claim 33, wherein a controller responsive to the sensor is configured to alter the selected pH range in the two or more levels of pulmonary tissue of the subject.

37. The method of claim 33, wherein the monitoring sensor is in an airway passage of the subject.

38. The method of claim 37, wherein the monitoring sensor is in a sinus or a nostril of the subject.

39. The method of claim 34, further including a pH-sensitive detection component in the pharmaceutical composition, the pH-sensitive detection component configured to communicate to the pH-monitoring sensor.

40. The method of claim 39, wherein the pH-sensitive detection component releases a marker indicating a pH range, and the pH-monitoring sensor is configured to recognize the marker.

41. The method of claim 39, wherein the pharmaceutical composition including the at least one agent is administered in response to information from the pH-sensitive detection component.

42. The method of claim 1, wherein the subject is mammalian or avian.

43-167. -167. (canceled)