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Generated: August 17, 2017
| Title: | Non-invasive methods for surgery in the vasculature |
| Abstract: | Novel methods of non-invasive intravascular surgery are disclosed, which include the intravascular administration of a composition comprising gas or gaseous precursor filled vesicles, followed by application of ultrasound in an amount sufficient to induce activation or rupture of the vesicles. The methods optionally also include the step of scanning the patient with diagnostic imaging to determine the presence of the vesicles in the region. |
| Inventor(s): | Unger; Evan C. (Tucson, AZ) |
| Assignee: | ImaRx Therapeutics, Inc. (Tucson, AZ) |
| Filing Date: | May 10, 2001 |
| Application Number: | 09/852,421 |
| Claims: | 1. A non-invasive method for performing surgery in the vasculature of a patient, said method comprising: (a) administering intravascularly to said patient a composition comprising, in an aqueous diluent, vesicles comprising a gas or gaseous precursor and a stabilizing compound; and (b) applying ultrasound to said patient in an amount sufficient to induce activation or rupture of said vesicles. 2. A method according to claim 1 wherein said activation or rupture of said vesicles results in the disruption or destruction of tissue within the vasculature of said patient. 3. A method according to claim 2 further comprising the step of scanning the patient with diagnostic imaging to ascertain the presence of said vesicles adjacent to said tissue. 4. A method according to claim 3 wherein said diagnostic imaging comprises magnetic resonance imaging. 5. A method according to claim 2 wherein said tissue comprises a thrombus. 6. A method according to claim 5 wherein said surgery alleviates a thrombosis in said patient. 7. A method according to claim 2 wherein said surgery repairs an aperture in said vasculature. 8. A method according to claim 1 wherein said vesicles further comprise a targeting ligand. 9. A method according to claim 1 wherein said vesicles further comprise a therapeutic agent which is released upon application of said ultrasound. 10. A method according to claim 1 wherein said gas or gaseous precursor comprises a fluorinated compound. 11. A method according to claim 10 wherein said fluorinated compound is selected from the group consisting of perfluorocarbons and sulfur hexafluoride. 12. A method according to claim 11 wherein said fluorinated compound is a perfluorocarbon selected from the group consisting of perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoromethane, perfluoroethane, perfluorohexane, and perfluoropentane. 13. A method according to claim 12 wherein said fluorinated compound is perfluoropropane. 14. A method according to claim 12 wherein said fluorinated compound is perfluorobutane. 15. A method according to claim 1 wherein said vesicles comprise liposomes. 16. A method according to claim 15 wherein said liposomes comprise crosslinked or polymerized lipids. 17. A method according to claim 15 wherein said liposomes comprise a phospholipid. 18. A method according to claim 15 wherein said liposomes further comprise polyethylene glycol. 19. A method according to claim 15 wherein said liposomes comprise a monolayer. 20. A method according to claim 1 wherein said vesicles comprise a polysaccharide. 21. A method according to claim 20 wherein said polysaccharide comprises galactose. 22. A method according to claim 1 wherein said vesicles comprise a polymer. 23. A method according to claim 22 wherein said polymer comprises a methacrylate. 24. A method according to claim 1 wherein said vesicles comprise a surfactant. 25. A method according to claim 24 wherein said vesicles have been rehydrated from lyophilized vesicles. 26. A method according to claim 1 wherein said vesicles comprise a protein. 27. A method according to claim 26 wherein said protein comprised albumin. 28. A method according to claim 4 wherein said composition further comprises a paramagnetic agent. 29. A method according to claim 28 wherein the paramagnetic agent comprises a paramagnetic ion selected from the group consisting of transition, lanthanide and actinide elements. 30. A method according to claim 29 wherein the paramagnetic ion is selected from the group consisting of Gd(III), Mn(II), Cu(II), Cr(III), Fe(II), Fe(III), Co(II), Er(II), Ni(II), Eu(III) and Dy(III). 31. A method according to claim 30 wherein the paramagnetic ion is Mn(II). 32. A method according to claim 28 wherein the paramagnetic agent comprises a nitroxide. 33. A method according to claim 4 wherein said composition comprises a superparamagnetic agent. 34. A method according to claim 33 wherein the superparamagnetic agent comprises a metal oxide or metal sulfide. 35. A method according to claim 34 wherein the superparamagnetic agent comprises a metal oxide wherein the metal is iron. 36. A method according to claim 35 wherein the superparamagnetic agent is selected from the group consisting of ferritin, iron, magnetic iron oxide, .gamma.-Fe.sub.2 O.sub.3, manganese ferrite, cobalt ferrite and nickel ferrite. 37. A method according to claim 4 wherein said vesicles are filled with .sup.19 F and said magnetic resonance imaging is nuclear magnetic resonance. 38. A method according claim 4 wherein said vesicles are filled with a gas selected from the group consisting of rubidium enhanced xenon, rubidium enhanced argon, rubidium enhanced helium, and rubidium enhanced neon. 39. A method according to claim 1 wherein said vesicles have a mean diameter less than about 30 microns. 40. A method according to claim 39 wherein said vesicles have a mean diameter less than about 12 microns. 41. A non-invasive method for the disruption of tissue in the vasculature of a patient, said method comprising: (a) administering intravascularly to said patient a composition comprising, in an aqueous diluent, vesicles comprising a gas or gaseous precursor and a stabilizing compound; (b) scanning the patient with diagnostic imaging to ascertain the presence of said vesicles adjacent to said tissue; and (c) applying ultrasound to said patient in an amount sufficient to induce activation or rupture of said vesicles adjacent to said tissue. 42. A method according to claim 41 wherein said method results in the alleviation of diseased tissue in said vasculature. 43. A method according to claim 42 wherein said method results in the alleviation of a thrombus in said vasculature. 44. A method according to claim 41 wherein said diagnostic imaging comprises magnetic resonance imaging. 45. A method according to claim 41 wherein said vesicles further comprise a targeting ligand. 46. A method according to claim 41 wherein said vesicles further comprise a therapeutic agent which is released upon application of said ultrasound. 47. A method according to claim 41 wherein said gas or gaseous precursor comprises a fluorinated compound. 48. A method according to claim 47 wherein said fluorinated compound is selected from the group consisting of perfluorocarbons and sulfur hexafluoride. 49. A method according to claim 48 wherein said fluorinated compound is a perfluorocarbon selected from the group consisting of perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoromethane, perfluoroethane, perfluorohexane, and perfluoropentane. 50. A method according to claim 49 wherein said fluorinated compound is perfluoropropane. 51. A method according to claim 49 wherein said fluorinated compound is perfluorobutane. 52. A method according to claim 41 wherein said vesicles comprise liposomes. 53. A method according to claim 52 wherein said liposomes comprise crosslinked or polymerized lipids. 54. A method according to claim 52 wherein said liposomes comprise a phospholipid. 55. A method according to claim 52 wherein said liposomes further comprise polyethylene glycol. 56. A method according to claim 52 wherein said liposomes comprise a monolayer. 57. A method according to claim 41 wherein said vesicles comprise a polysaccharide. 58. A method according to claim 57 wherein said polysaccharide comprises galactose. 59. A method according to claim 41 wherein said vesicles comprise a polymer. 60. A method according to claim 59 wherein said polymer comprises a methacrylate. 61. A method according to claim 41 wherein said vesicles comprise a surfactant. 62. A method according to claim 61 wherein said vesicles have been rehydrated from lyophilized vesicles. 63. A method according to claim 41 wherein said vesicles comprise a protein. 64. A method according to claim 62 wherein said protein comprised albumin. 65. A method according to claim 44 wherein said composition further comprises a paramagnetic agent. 66. A method according to claim 65 wherein the paramagnetic agent comprises a paramagnetic ion selected from the group consisting of transition, lanthanide and actinide elements. 67. A method according to claim 66 wherein the paramagnetic ion is selected from the group consisting of Gd(III), Mn(II), Cu(II), Cr(III), Fe(II), Fe(III), Co(II), Er(II), Ni(II), Eu(III) and Dy(III). 68. A method according to claim 67 wherein the paramagnetic ion is Mn(II). 69. A method according to claim 66 wherein the paramagnetic agent comprises a nitroxide. 70. A method according to claim 44 wherein said composition comprises a superparamagnetic agent. 71. A method according to claim 70 wherein the superparamagnetic agent comprises a metal oxide or metal sulfide. 72. A method according to claim 71 wherein the superparamagnetic agent comprises a metal oxide wherein the metal is iron. 73. A method according to claim 72 wherein the superparamagnetic agent is selected from the group consisting of ferritin, iron, magnetic iron oxide, .gamma.-Fe.sub.2 O.sub.3, manganese ferrite, cobalt ferrite and nickel ferrite. 74. A method according to claim 44 wherein said vesicles are filled with .sup.19 F and said magnetic resonance imaging is nuclear magnetic resonance. 75. A method according claim 44 wherein said vesicles are filled with a gas selected from the group consisting of rubidium enhanced xenon, rubidium enhanced argon, rubidium enhanced helium, and rubidium enhanced neon. 76. A method according to claim 41 wherein said vesicles have a mean diameter less than about 30 microns. 77. A method according to claim 76 wherein said vesicles have a mean diameter less than about 12 microns. |
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