Oxygen delivery agents and uses for the same

• US 6,537,246 B1
• Filed: 06/18/1997
• Issued: 03/25/2003
• Est. Priority Date: 06/18/1997
• Status: Expired due to Fees

• Current Assignee: Cerevast Therapeutics, Inc.
• Original Assignee: Imarx Therapeutics, Inc. (Sycamore Entertainment Group, Inc.)
• Inventors: Unger, Evan C., Wu, Yunqiu, McCreery, Thomas
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US08/877,826
• Time in Patent Office: 2,106 Days
• Field of Search: 424/450, 428/402.2, 436/829, 604/82, 604/24, 222/129, 222/146.1, 222/146.2, 222/145.5, 222/145.6
• US Class Current: 604/82
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 47/544 Phospholipids
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911

Abstract

The present invention describes, inter alia, oxygen delivery agents or blood substitutes comprising a fluorinated gas and a stabilizing material, uses for the oxygen delivery agents or blood substitutes, and apparatus for making and delivering the oxygen delivery agents or blood substitutes.

Claims

1. An apparatus for making an oxygen delivery agent, comprising:

a first syringe containing a stabilizing material;

a second syringe containing a fluorinated compound;

means for simultaneously evacuating said first and second syringes;

means for mixing said stabilizing material and said fluorinated compound evacuated from said first and second syringes so as to form a mixture.

2. The apparatus according to claim 1 further comprising a supply of oxygen;

and means for introducing oxygen from said supply into said mixture so as to form an oxygen delivery agent.

3. The apparatus according to claim 2, wherein said stabilizing material comprises an aqueous solution containing lipids, whereby said mixing means forms an aqueous solution containing lipids filled with said fluorinated compound, and wherein said oxygen introducing means causes said fluorinated compound filled lipids to become further filled with said oxygen.

4. The apparatus according to claim 2, further comprising a conduit for delivering said oxygen delivery agent to a patient.

5. The apparatus according to claim 4, wherein said means for introducing said oxygen into said mixture comprises means for directing said oxygen from said supply into said conduit.

6. The apparatus according to claim 2, wherein said means for introducing said oxygen into said mixture comprises means for directing said oxygen from said supply into one of said first and second syringes.

7. The apparatus according to claim 6, wherein said oxygen supply comprises a third vessel, and wherein said means for directing said oxygen into one of said first and second syringes comprises means for piercing said third vessel.

8. The apparatus according to claim 7, wherein said means for piercing said third vessel comprises a threaded joint.

9. The apparatus according to claim 7, wherein the means for evacuating said first and second syringes comprises a third vessel containing a supply of pressurized gas.

10. The apparatus according to claim 1, wherein said mixing means comprises means for inducing turbulence in said mixture.

11. The apparatus according to claim 10, wherein said turbulence inducing means comprises a static mixer.

12. The apparatus according to claim 11, wherein said static mixer comprises a helical baffle disposed within a conduit through which said mixture flows.

13. The apparatus according to claim 1, wherein said mixing means comprises means for agitating said mixture.

14. The apparatus according to claim 1, wherein said mixing means comprises means for generating pressure waves directed toward said mixture.

15. The apparatus according to claim 14, wherein said pressure wave generating means comprises means for generating pressure waves in the ultrasonic frequency range.

16. The apparatus according to claim 15, wherein said pressure wave generating means comprises means for generating pressure waves in the approximately 20 KHz to 5 MHz frequency range.

17. The apparatus according to claim 14, wherein said pressure wave generating means comprises a transducer.

18. The apparatus according to claim 14, wherein said pressure wave generating means comprises a chamber, said chamber enclosing a conduit through which said mixture flows.

19. The apparatus according to claim 18, wherein said pressure wave generating means further comprises means for facilitating transmission of said pressure waves through said chamber.

20. The apparatus according to claim 19, wherein said pressure wave generating means further comprises a transducer, and wherein said pressure wave transmission facilitating means comprises a medium disposed within said chamber between said conduit and said transducer.

21. The apparatus according to claim 18, wherein said pressure wave generating means further comprises at least first and second transducers mounted on said chamber.

22. The apparatus according to claim 21, wherein said first transducer has means for operating at a frequency lower than said second transducer.

23. The apparatus according to claim 21, wherein said first and second transducers have overlapping focal zone, and wherein said first transducer has means for operating at a first frequency and said second transducer has means for operating at a second frequency, said second frequency being an integer multiple of said first frequency.

24. The apparatus according to claim 1, wherein said mixing means comprises means for bringing said fluorinated compound and said stabilizing material into contact with each other.

25. The apparatus according to claim 24, wherein said contacting means comprises a section of tubing having first and second branches in flow communication with said first and second syringes, respectively.

26. The apparatus according to claim 24, wherein said mixing means further comprises a static mixer.

27. The apparatus according to claim 26, wherein said mixing means further comprises a pressure transducer.

28. The apparatus according to claim 27, wherein said pressure transducer has means for operating in the ultrasonic frequency range.

29. The apparatus according to claim 1, further comprising means for heating said mixture.

30. The apparatus according to claim 29, wherein said heating means has means for heating said mixture to at least approximately 37°

C.

31. The apparatus according to claim 1, wherein said means for evacuating comprises means for driving a plunger.

32. The apparatus according to claim 31, wherein said means for driving said plunger comprises pressurized gas.

33. The apparatus according to claim 32, further comprising a third vessel, said third vessel containing said pressurized gas, and wherein said means for driving said plunger further comprises means for piercing said third vessel.

34. The apparatus according to claim 33, wherein said piercing means comprises a threaded joint.

35. The apparatus according to claim 1, wherein said fluorinated compound in said second syringe is a fluorinated gas.

36. The apparatus according to claim 1, wherein said fluorinated compound in said second syringe is a fluorinated gaseous precursor.

37. The apparatus according to claim 36, further comprising means for converting said gaseous precursor to a gas.

38. The apparatus according to claim 37, wherein said means for converting said gaseous precursor to a gas comprises means for generating pressure waves directed toward said gaseous precursor.

39. The apparatus according to claim 38, wherein said pressure waves are generated at a frequency in the ultrasonic range.

40. The apparatus according to claim 38, wherein said pressure wave generating means comprises a first transducer.

41. The apparatus according to claim 40, wherein said pressure wave generating means further comprises a second transducer, and wherein said first transducer has means for operating at a first frequency and said second transducer has means for operating at a second frequency, said first frequency being lower than said second frequency.

42. The apparatus according to claim 41, wherein said second frequency is an integer multiple of said first frequency.

43. The apparatus according to claim 2, wherein said oxygen delivery agent is in the form of a vesicle, and further comprising means for regulating the size of said vesicle.

44. The apparatus according to claim 43, wherein said sizing means comprises a filter.

45. The apparatus according to claim 43, wherein said sizing means comprises means for generating pressure waves.

46. The apparatus according to claim 45, wherein said pressure wave generating means comprises means for generating pressure waves in the ultrasonic frequency range.

47. The apparatus according to claim 46, wherein said pressure wave generating means comprises means for generating pressure waves in the approximately 20 KHz to 5 MHz frequency range.

48. The apparatus according to claim 45, wherein said pressure wave generating means comprises a transducer.