Aerosol device to deliver bioactive agent

• US 20030181917A1
• Filed: 01/24/2003
• Published: 09/25/2003
• Est. Priority Date: 01/24/2002
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Gertner, Michael E.
• Granted Patent: US 7,544,177 B2
• Time in Patent Office: Days
• US Class Current: 606/82
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 2017/00522 Sprayers
• CPC Class Codes: A61B 2017/00889 antimicrobial, disinfectant
• CPC Class Codes: A61B 2017/00893 pharmaceutically effective
• CPC Class Codes: A61M 11/06 of the injector type
• CPC Class Codes: A61M 13/00 Insufflators for therapeutic or disinfectant purposes , i.e. devices for blowing a gas, powder or vapour into the body hand-held units in which gas flow is produced by muscular energy at the moment of use B05B11/062
• CPC Class Codes: A61M 15/0066 with means for varying the dose size
• CPC Class Codes: A61M 2202/0007 introduced into the body
• CPC Class Codes: A61M 2202/0468 non-physiological
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/8225 using incorporated gas cartridges for the driving gas
• CPC Class Codes: A61M 2209/06 Packaging for specific medical equipment
• CPC Class Codes: A61M 35/003 Portable hand-held applicators having means for dispensing or spreading integral media hand-held massage devices with liquid delivery A61H7/003
• CPC Class Codes: A61M 35/30 Gas therapy for therapeutic treatment of the skin
• CPC Class Codes: B05B 7/2424 the carried liquid and the main stream of atomising fluid being brought together downstream of the container before discharge B05B7/2435 takes precedence
• CPC Class Codes: B05B 7/2443 the carried liquid and the main stream of carrying liquid being brought together downstream of the container before discharge B05B7/2454 takes precedence

Abstract

This invention provides surgical devices and methods to apply bioactive agents to surgical sites. The devices include, e.g., a body for attachment of a pressurized fluid vessel and a reservoir of bioactive agent for controlled spraying of an aerosol of bioactive agent.

Claims

1. A handheld surgical device comprising in combination:

a body including;

a means for receiving a pressurized fluid vessel;

a means for receiving a reservoir;

an outlet port;

a valve that regulates flow of a fluid through said means for receiving a pressurized fluid vessel; and

a channel that communicates between said means for receiving a pressurized fluid vessel, said means for receiving a reservoir, and said outlet port;

said channel comprising a mixing chamber, whereby fluid passing from the means for receiving a pressurized gas vessel to said outlet port mixes with a bioactive agent flowing from said means for receiving a reservoir resulting in said agent and said fluid exiting the device through said outlet port.

2. The device of claim 1, wherein said device further comprises a pressurized fluid vessel permanently affixed or removably affixed to said means for receiving said pressurized fluid vessel.

3. The device of claim 2, wherein said pressurized fluid vessel comprises a pressurized fluid.

4. The device of claim 3, wherein said pressurized fluid is selected from the group consisting of carbon dioxide, nitrogen, argon, helium, atmospheric air, liquefied gasses, and liquid propellants.

5. The device of claim 2, wherein said device comprises a means for regulating the mixing proportions between an agent from a reservoir attached to said means for attaching a reservoir and fluid from the pressurized fluid vessel.

6. The device of claim 1, wherein said device further comprises a reservoir removably affixed to said means for receiving a reservoir.

7. The device of claim 6, wherein said reservoir contains one or more bioactive agents.

8. The device of claim 7, wherein said reservoir comprises a means for regulating the rate of aspiration of the bioactive agent from said reservoir.

9. The device of claim 8, wherein said means for regulating comprises an aperture adjustable from substantially non-communicating with the channel to a position of open communication with the channel.

10. The device of claim 7, wherein said one or more bioactive agents are selected from the group consisting of a hemostatic agent, an adhesion preventing compound, a nucleic acid, a protein, a muscle contraction stimulator, an anti-inflammatory compound, a vaccine, an enzyme, a growth factor, and a nanoparticle.

11. The device of claim 7, wherein said one or more bioactive agents comprise a hemostatic agent selected from the group consisting of collagen, fibrin, thrombin, fibrinogen, tissue factor, or a non-organic hemostasis activator.

12. The device of claim 7, wherein said one or more bioactive agents comprise an adhesion-preventing agent selected from the group consisting of polyethylene glycol and derivatives, polylactic acid, polyglycolic acid, hyaluronic acid, paclitaxel and derivatives, or sirolimus and derivatives.

13. The device of claim 7, wherein said one or more bioactive agents are dry.

14. The device of claim 7, wherein said one or more bioactive agents are associated with a carrier macromolecule.

15. The device of claim 1, wherein said channel comprises a Venturi constriction.

16. The device of claim 1, further comprising a nozzle attached to said outlet port.

17. The device of claim 16, wherein said nozzle is an adjustable nozzle.

18. The device of claim 16, wherein said nozzle is a removable nozzle.

19. The device of claim 1, wherein said device further comprises a handgrip.

20. The device of claim 1, wherein said device is fabricated from one or more materials selected from the group consisting of metal, polymer, and ceramic.

21. The device of claim 1, wherein said device comprises a nozzle, or a nozzle affixed to a tube, that can be inserted through a trocar in a laparoscopic procedure.

22. The device of claim 1, wherein said device is tolerant of the temperature and moisture in an autoclave.

23. The device of claim 1, wherein said device is tolerant of the radiation in a microwave oven or a device for sterilization by ionizing radiation.

24. The device of claim 1, wherein said device is substantially sterile.

25. The device of claim 1, wherein said device comprises a:

a pressurized fluid vessel affixed to said means for receiving a pressurized fluid vessel;

a reservoir affixed to said means for receiving a reservoir, wherein said reservoir contains a bioactive agent; and

a handgrip.

66. A method of locally administering a bioactive agent, said method comprising:

coupling a reservoir comprising a bioactive agent to the device of any of claims 1, 26; and

51; and

activating said device to apply the bioactive agent as an aerosol onto a surgical site.

67. The method of claim 66, wherein said aerosol is a suspension of bioactive agent in a fluid stream of carbon dioxide gas.

68. The method of claim 66, wherein said activating further comprises operating said device to aspirate said bioactive agent from said reservoir and aerosolize said agent in a fluid stream of gas.

69. The method of claim 66, further comprising clearing or drying the surgical site with a stream of gas from the device.

70. The method of claim 68, wherein said fluid stream of gas is directed to a bleeding surface.

71. The method of claim 70, wherein said bioactive agent is a hemostatic agent.

72. The method of claim 71, wherein said bioactive agent is a hemostatic agent selected from the group consisting of collagen, fibrin, thrombin, fibrinogen, tissue factor, and a non-organic surface to promote hemostasis indirectly.

73. The method of claim 68, wherein said fluid stream is directed to a surface of bowel, peritoneum, heart, lungs, spleen, pancreas, colon, stomach, muscle, thyroid gland, parathyroid gland, brain, adrenal gland, prostate gland, esophagus, or ureteral tract.

74. The method of claim 73, wherein said bioactive agent is an adhesion-preventing agent.

75. The method of claim 74, wherein said bioactive agent is an adhesion-preventing agent selected from the group consisting of polyethylene glycol and derivatives, polylactic acid, polyglycolic acid, hyaluronic acid, rapamycin (sirolimus), paclitaxel, and cyclosporine.

76. The method of claim 66, wherein said bioactive agent is contained within said reservoir in a substantially dry form.

77. A method of coupling a reservoir comprising a bioactive agent to the device of any of claims 1, 26;

and 51; and

activating said device to apply sufficient momentum to a combination of pressurized fluid and bioactive agent to substantially penetrate a surface of an organ with bioactive agent.

80. A kit for clearing an operative field and optionally administering a bioactive agent, said kit comprising:

a container containing a device according to any of claims 1, 26, and 51.

81. The kit of claim 80, wherein said container is tolerant of the temperature and moisture in an autoclave.

82. The kit of claim 80, wherein said container is tolerant of ionizing radiation or a radiation produced within a microwave oven.

83. The kit of claim 80, wherein said device is substantially sterile.

84. The kit of claim 80, further comprising instructional materials teaching the use of said device to clear an operative field and, optionally, to administer a bioactive agent to a tissue in said operative field.

85. A kit for administering a bioactive agent to a tissue, said kit comprising:

a reservoir containing a dry bioactive agent formulated to aerosolize in a fluid stream where said reservoir comprises a means for removable attachment to a device according to any of claims 1, 26, and 51.

86. The kit of claim 85, wherein said kit further comprises the device.

87. The kit of claim 85, wherein said reservoir comprises a means for regulating the rate of aspiration of said bioactive agent from said reservoir.

88. The kit of claim 85, wherein said bioactive agent comprises a hemostatic agent selected from the group consisting of collagen, fibrin, thrombin, and fibrinogen.

89. The kit of claim 85, wherein said bioactive agent comprises an adhesion-preventing agent selected from the group consisting of polyethylene glycol and derivatives, polylactic acid, polyglycolic acid, hyaluronic acid, paclitaxel and derivatives, and sirolimus and derivatives.

90. The kit of claim 85, wherein said bioactive agent is dry.

91. The kit of claim 85, wherein said bioactive agent is associated with a macromolecule.

92. The kit of claim 85, further comprising instructional materials teaching the use of said device to clear an operative field and, optionally, to administer a bioactive agent to a tissue in said operative field.

26. A surgical device comprising in combination:

a body including;

a removably, or permanently affixed pressurized fluid vessel;

a means for receiving a reservoir;

an outlet port;

a channel that communicates between pressurized fluid vessel, said means for receiving a reservoir, and said outlet port, said channel comprising a Venturi constriction whereby gas passing from the means for receiving a pressurized gas vessel to said outlet port aspirates agent through said means for receiving a reservoir resulting in said agent and said gas exiting the device through said outlet port.

27. The device of claim 26, further comprising a valve that regulates flow of a fluid from said pressurized fluid vessel through said outlet port.

28. The device of claim 26, wherein said removably or permanently affixed pressurized fluid vessel is a permanently affixed pressurized fluid vessel.

29. The device of claim 26, wherein said pressurized fluid vessel is integral with said body.

30. The device of claim 26, wherein said pressurized fluid vessel comprises a means for connecting said vessel to a pressurized gas source to charge said vessel.

31. The device of claim 26, wherein said fluid vessel comprises a pressurized fluid.

32. The device of claim 31, wherein said pressurized fluid is selected from the group consisting of carbon dioxide, nitrogen, argon, and helium.

33. The device of claim 26, wherein said device further comprises a reservoir removably affixed to said means for receiving a reservoir.

34. The device of claim 33, wherein said reservoir contains one or more bioactive agents.

35. The device of claim 26, wherein said device comprises a means for regulating the rate of aspiration of an agent from a reservoir attached to said means for attaching a reservoir.

36. The device of claim 33, wherein said reservoir comprises a means for regulating the rate of aspiration of an agent from said reservoir.

37. The device of claim 26, wherein said Venturi constriction comprises an aperture adjustable from completely non-communicating with the channel to a position of communication with the channel.

38. The device of claim 34, wherein said one or more bioactive agents are selected from the group consisting of a hemostatic agent, an adhesion preventing compound, a nucleic acid, and a protein.

39. The device of claim 34, wherein said one or more bioactive agents comprise a hemostatic agent selected from the group consisting of collagen, fibrin, thrombin, and fibrinogen.

40. The device of claim 34, wherein said one or more bioactive agents comprise an adhesion-preventing agent selected from the group consisting of polyethylene glycol and derivatives, polylactic acid, polyglycolic acid, hyaluronic acid, paclitaxel and derivatives, and sirolimus and derivatives.

41. The device of claim 34, wherein said one or more bioactive agents is pegylated.

42. The device of claim 26, further comprising an adjustable and/or removable nozzle attached to said outlet port.

43. The device of claim 42, wherein said nozzle is an adjustable nozzle.

44. The device of claim 42, wherein said nozzle is a removable nozzle.

45. The device of claim 26, wherein said device further comprises a handgrip.

46. The device of claim 26, wherein said device is fabricated from one or more materials selected from the group consisting of metal, plastic, and ceramic.

47. The device of claim 26, wherein said device comprises a nozzle or a nozzle affixed to a tube that can be inserted through a port in a laparoscopic procedure.

48. The device of claim 26, wherein said device is tolerant of the temperature and moisture in an autoclave.

49. The device of claim 26, wherein said device is tolerant of the radiation in a microwave oven.

50. The device of claim 26, wherein said device is substantially sterile.

51. A device comprising:

a pressurized fluid vessel comprising a bioactive agent suspended or dissolved in a pressurized fluid within said vessel;

a nozzle in fluid communication with said pressurized fluid vessel; and

a valve to regulate the flow rate of said pressurized fluid through said nozzle.

52. The device of claim 51, wherein said pressurized fluid is selected from the group consisting of carbon dioxide, nitrogen, argon, helium, and compressed air.

53. The device of claim 51, wherein said one or more bioactive agents are selected from the group consisting of a hemostatic agent, an adhesion preventing compound, a nucleic acid, and a protein.

54. The device of claim 51, wherein said one or more bioactive agents comprise a hemostatic agent selected from the group consisting of collagen, fibrin, thrombin, and fibrinogen.

55. The device of claim 51, wherein said one or more bioactive agents comprise an adhesion-preventing agent selected from the group consisting of polyethylene glycol and derivatives, polylactic acid, polyglycolic acid, hyaluronic acid paclitaxel and derivatives, and sirolimus and derivatives.

56. The device of claim 51, wherein said one or more bioactive agents is associated with a macromolecule.

57. The device of claim 51, wherein said nozzle is an adjustable nozzle.

58. The device of claim 51, wherein said nozzle is a removable nozzle.

59. The device of claim 51, wherein said device further comprises a handgrip.

60. The device of claim 51, wherein said device is fabricated from one or more materials selected from the group consisting of metal, polymer, ceramic, and composite.

61. The device of claim 51, wherein said device comprises a nozzle or a nozzle affixed to a tube that can be inserted through a port in a laparoscopic procedure.

62. The device of claim 51, wherein said device comprises a flexible extension suitable for insertion through an endoscope, bronchoscope, arthroscope, ureteroscope, catheter, or vascular access device.

63. The device of claim 51, wherein said device is tolerant of the temperature and moisture in an autoclave.

64. The device of claim 51, wherein said device is tolerant of the radiation in a microwave oven.

65. The device of claim 51, wherein said device is substantially sterile.

78. The method of 77, wherein said organ is one or more of the group comprising liver, kidneys, small bowel, colon, rectum, lungs, heart, brain, spleen, or pancreas.

79. The method of 78, wherein said bioactive agent comprises a gene plasmid, a complementary mRNA, or an interfering double stranded RNA.