Permanent, removable tissue markings

• US 20050178287A1
• Filed: 11/09/2004
• Published: 08/18/2005
• Est. Priority Date: 11/20/1998
• Status: Active Grant

• Current Assignee: Craig A. Drill, Freedom-2, Inc., The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Freedom-2, Inc., The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Anderson, Richard Rox, Drill, Craig A., Mlynarczyk-Evans, Susanna K.
• Granted Patent: US 7,175,950 B2
• Time in Patent Office: Days
• US Class Current: 106/31.30
• CPC Class Codes: A61K 2800/412 Microsized, i.e. having sizes between 0.1 and 100 microns
• CPC Class Codes: A61K 2800/438 Thermochromatic; Photochromic; Phototropic
• CPC Class Codes: A61K 2800/56 Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
• CPC Class Codes: A61K 2800/624 by macromolecular compounds
• CPC Class Codes: A61K 8/0241 Containing particulates characterized by their shape and/or structure see also A61K8/04, A61K8/11, and A61K8/14, further aspects are classified in A61K2800/40 and subcodes
• CPC Class Codes: A61Q 1/025 Semi-permanent tattoos, stencils, e.g. "permanent make-up"
• CPC Class Codes: A61Q 19/04 for chemically tanning the skin topical sun or radiation screening or tanning preparations A61Q17/04
• CPC Class Codes: C09D 11/00 Inks
• CPC Class Codes: C09D 11/02 Printing inks C09D11/30 takes precedence
• CPC Class Codes: C09D 11/037 characterised by the pigment
• CPC Class Codes: C09D 11/50 Sympathetic, colour changing or similar inks
• CPC Class Codes: Y10S 430/145 Infrared
• CPC Class Codes: Y10S 430/165 Thermal imaging composition
• CPC Class Codes: Y10T 428/2991 Coated
• CPC Class Codes: Y10T 428/2993 Silicic or refractory material containing [e.g., tungsten oxide, glass, cement, etc.]

Abstract

While the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

1. A tissue marking particle comprising a chromophore, wherein an appearance of the chromophore changes upon exposure to a specific energy when the particle is within a tissue.

2. The particle of claim 1, wherein the chromophore is photobleachable.

3. The particle of claim 2, wherein the photobleachable chromophore comprises at least one of phthalocyanine, porphycene, chlorin, a rhodamine dye, porphyrin, Rose Bengal, a dye-paired ion compound, a cationic dye-borate anion complex, a coumarin compound, and a bis(diiminosuccinonitrilo)metal complex.

4. The particle of claim 3, wherein the chromophore comprises a 3-position-substituted coumarin compound.

5. The particle of claim 2, wherein the chromophore is photobleachable only upon simultaneous absorption of multiple photons.

6. The particle of claim 2, wherein the chromophore is photobleachable upon exposure to the specific energy.

7. The particle of claim 6, wherein the specific energy is infrared radiation.

8. The particle of claim 1, wherein the chromophore is thermolabile.

9. The particle of claim 1, wherein the chromophore is bleachable upon exposure to a bleaching agent.

10. The particle of claim 9, wherein the bleaching agent is a peroxide, a hypochlorite, an excited oxygen species, or a free radical.

11. The particle of claim 9, wherein the chromophore is pH-sensitive, and a bleaching agent is an acid, a base, or a buffer capable of effecting a pH transition within the particle to bleach the chromophore.

12. The particle of claim 1, wherein the specific energy is electromagnetic radiation.

13. The particle of claim 1, wherein the appearance of the chromophore changes when the specific energy is applied once.

14. The particle of claim 1, wherein the specific energy is infrared or near-infrared radiation.

15. The particle of claim 1, wherein the chromophore has an average particle size of less than about 50 nm.

16. The particle of claim 1, wherein the chromophore is selected from the group consisting of rifampin, β

-carotene, tetracycline, indocyanine green, Evan'"'"'s blue, methylene blue, FD&

C Blue No. 1 (Brilliant Blue FCF), FD&

C Green No. 3 (Fast Green FCF), FD&

C Red No. 3 (Erythrosine), FD&

C Red No. 40, FD&

C Yellow No. 5 (Tartrazine), FD&

C Yellow No. 6 (Sunset Yellow FCF), Rose Bengal, a rhodamine compound, a coumarin compound, a dye-paired ion compound, a cationic dye-borate anion complex, and a bis(diiminosuccino-nitrilo)metal complex.

17. The particle of claim 1, wherein the chromophore changes from an initial color to a different color upon exposure of the particle to the specific energy.

18. The particle of claim 1, wherein the particle further comprises:

(i) an indispersible, biologically inert coating; and

(ii) a core enveloped within the coating, wherein the core comprises the chromophore.

19. The particle of claim 18, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or a combination thereof.

20. The particle of claim 18, wherein the coating is substantially visibly transparent and absorbs near-infrared radiation.

21. The particle of claim 18, wherein multiple cores are enveloped within the coating of a single particle.

22. The particle of claim 21, wherein one of the cores comprises a bleaching agent and the chromophore is bleachable upon exposure to the bleaching agent.

23. The particle of claim 22, wherein the core containing the bleaching agent is enveloped in its own coating.

24. The particle of claim 23, wherein the core containing the bleaching agent or the coating enveloping it contains a discrete absorption component, which allows the bleaching agent to leach out and come into contact with the chromophore upon exposure to the specific energy.

25. The particle of claim 24, wherein the discrete absorption component is selected from the group consisting of Schott filter glass, graphite, carbon, a metal oxide, an acrylate polymer, and a urethane polymer.

26. The particle of claim 18, wherein the chromophore is detectable through the coating.

27. The particle of claim 18, wherein the coating comprises from about 10 to about 95 percent of the volume of the particle.

28. The particle of claim 1, wherein the particle is from about 50 nm to about 100 microns in size.

29. The particle of claim 1, wherein the particle is from about 15 nm to about 500 nm in size.

30. The particle of claim 1, wherein the particle is less than about 50 nm in size.

31. The particle of claim 30, wherein the particle is less than about 5 nm in size.

32. A tissue marking ink comprising the particle of claim 1 and a carrier.

33. The ink of claim 32, wherein the carrier comprises at least one of alcohol, water, or glycerin.

34. A method of applying a tissue marking, the method comprising:

providing a particle comprising a chromophore; and

implanting the particle into a tissue to form a tissue marking,

wherein an appearance of the chromophore changes upon exposure to a specific energy when the chromophore is within the tissue.

35. The method of claim 34, wherein the chromophore is photobleachable.

36. The method of claim 35, wherein the photobleachable chromophore comprises at least one of phthalocyanine, porphycene, chlorin, a rhodamine dye, porphyrin, Rose Bengal, a dye-paired ion compound, a cationic dye-borate anion complex, a coumarin compound, and a bis(diiminosuccinonitrilo)metal complex.

37. The method of claim 36, wherein the chromophore comprises a 3-position-substituted coumarin compound.

38. The method of claim 35, wherein the chromophore is photobleachable only upon simultaneous absorption of multiple photons.

39. The method of claim 35, wherein the chromophore is photobleachable upon exposure to the specific energy.

40. The method of claim 39, wherein the specific energy is infrared radiation.

41. The method of claim 35, wherein the chromophore is thermolabile.

42. The method of claim 35, wherein the chromophore is bleachable upon exposure to a bleaching agent.

43. The method of claim 42, wherein the bleaching agent is a peroxide, a hypochlorite, an excited oxygen species, or a free radical.

44. The method of claim 42, wherein the chromophore is pH-sensitive, and a bleaching agent is an acid, a base, or a buffer capable of effecting a pH transition within the particle to bleach the chromophore.

45. The method according claim 34, wherein the specific energy is electromagnetic radiation.

46. The method according claim 34, wherein the appearance of the chromophore changes when the specific energy is applied once.

47. The method of claim 34, wherein the specific energy is infrared or near-infrared radiation.

48. The method of claim 34, wherein the chromophore has an average particle size of less than about 50 nm.

49. The method of claim 34, wherein the chromophore is selected from the group consisting of rifampin, β

-carotene, tetracycline, indocyanine green, Evan'"'"'s blue, methylene blue, FD&

C Blue No. 1 (Brilliant Blue FCF), FD&

C Green No. 3 (Fast Green FCF), FD&

C Red No. 3 (Erythrosine), FD&

C Red No. 40, FD&

C Yellow No. 5 (Tartrazine), FD&

C Yellow No. 6 (Sunset Yellow FCF), Rose Bengal, a rhodamine compound, a coumarin compound, a dye-paired ion compound, a cationic dye-borate anion complex, and a bis(diiminosuccino-nitrilo)metal complex.

50. The method of claim 34, wherein the chromophore changes from an initial color to a different color upon exposure of the particle to the specific energy.

51. The method of claim 34, wherein the particle further comprises:

(i) an indispersible, biologically inert coating; and

(ii) a core enveloped within the coating, wherein the core comprises the chromophore.

52. The method of claim 51, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or a combination thereof.

53. The method of claim 51, wherein the coating is substantially visibly transparent and absorbs near-infrared radiation.

54. The method of claim 51, wherein multiple cores are enveloped within the coating of a single particle.

55. The method of claim 54, wherein one of the cores comprises a bleaching agent and the chromophore is bleachable upon exposure to the bleaching agent.

56. The method of claim 55, wherein the core containing the bleaching agent is enveloped in its own coating.

57. The method of claim 56, wherein the core containing the bleaching agent or the coating enveloping it contains a discrete absorption component, which allows the bleaching agent to leach out of the core and come into contact with the chromophore upon exposure to the specific energy.

58. The method of claim 57, wherein the discrete absorption component is selected from the group consisting of Schott filter glass, graphite, carbon, a metal oxide, an acrylate polymer, and a urethane polymer.

59. The method of claim 51, wherein the chromophore is detectable through the coating.

60. The method of claim 51, wherein the coating comprises from about 10 to about 95 percent of the volume of the particle.

61. The method of claim 34, wherein the particle is from about 50 nm to about 100 microns in size.

62. The method of claim 34, wherein the particle is from about 15 nm to about 500 nm in size.

63. The method of claim 34, wherein the particle is less than about 50 nm in size.

64. The method of claim 63, wherein the particle is less than about 5 nm in size.

65. A method for altering a tissue marking implanted in tissue, the tissue marking comprising a particle comprising a chromophore, wherein an appearance of the chromophore changes upon exposure to a specific energy when the chromophore is within the tissue, the method comprising exposing the tissue marking to the specific energy for a sufficient time to change the appearance of the chromophore.

66. The method of claim 65, wherein the chromophore is photobleachable.

67. The method of claim 66, wherein the photobleachable chromophore comprises at least one of phthalocyanine, porphycene, chlorin, a rhodamine dye, porphyrin, Rose Bengal, a dye-paired ion compound, a cationic dye-borate anion complex, a coumarin compound, and a bis(diiminosuccinonitrilo)metal complex.

68. The method of claim 67, wherein the chromophore comprises a 3-position-substituted coumarin compound.

69. The method of claim 66, wherein the chromophore is photobleachable only upon absorption of multiple photons.

70. The method of claim 66, wherein the chromophore is photobleached upon exposure to the specific energy.

71. The method of claim 70, wherein the specific energy is infrared radiation.

72. The method of claim 65, wherein the chromophore is thermolabile.

73. The method of claim 65, wherein the chromophore is bleachable upon exposure to a bleaching agent.

74. The method of claim 73, wherein the bleaching agent is a peroxide, a hypochlorite, an excited oxygen species, or a free radical.

75. The method of claim 73, wherein the chromophore is pH-sensitive, and the bleaching agent is an acid, a base, or a buffer capable of effecting a pH transition within the particle to bleach the chromophore.

76. The method according claim 65, wherein the specific energy is electromagnetic radiation.

77. The method according claim 65, wherein the appearance of the chromophore changes when the specific energy is applied once.

78. The method of claim 65, wherein the specific energy is infrared or near-infrared radiation.

79. The method of claim 65, wherein the chromophore has an average particle size of less than about 50 nm.

80. The method of claim 65, wherein the chromophore is selected from the group consisting of rifampin, β

-carotene, tetracycline, indocyanine green, Evan'"'"'s blue, methylene blue, FD&

C Blue No. 1 (Brilliant Blue FCF), FD&

C Green No. 3 (Fast Green FCF), FD&

C Red No. 3 (Erythrosine), FD&

C Red No. 40, FD&

C Yellow No. 5 (Tartrazine), FD&

C Yellow No. 6 (Sunset Yellow FCF), Rose Bengal, a rhodamine compound, a coumarin compound, a dye-paired ion compound, a cationic dye-borate anion complex, and a bis(diiminosuccino-nitrilo)metal complex.

81. The method of claim 65, wherein exposure of the particle to the specific energy changes a color of the chromophore.

82. The method of claim 65, wherein the particle further comprises:

(i) an indispersible, biologically inert coating; and

(ii) a core enveloped within the coating, wherein the core comprises the chromophore.

83. The method of claim 82, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or a combination thereof.

84. The method of claim 82, wherein the coating is substantially visibly transparent and absorbs near-infrared radiation.

85. The method of claim 82, wherein multiple cores are enveloped within the coating of a single particle.

86. The method of claim 85, wherein one of the cores comprises a bleaching agent and the chromophore is bleachable upon exposure to the bleaching agent.

87. The method of claim 86, wherein the core containing the bleaching agent is enveloped in its own coating.

88. The method of claim 87, wherein the core containing the bleaching agent or the coating enveloping it contains a discrete absorption component, which allows the bleaching agent to leach out and come into contact with the chromophore upon exposure to the specific energy.

89. The method of claim 88, wherein the discrete absorption component is selected from the group consisting of Schott filter glass, graphite, carbon, a metal oxide, an acrylate polymer, and a urethane polymer.

90. The method of claim 82, wherein the chromophore is detectable through the coating.

91. The method of claim 82, wherein the coating comprises from about 10 to about 95 percent of the volume of the particle.

92. The method of claim 65, wherein the particle is from about 50 nm to about 100 microns in size.

93. The method of claim 65, wherein the particle is from about 15 nm to about 500 nm in size.

94. The method of claim 65, wherein the particle is less than about 50 nm in size.

95. The method of claim 94, wherein the particle is less than about 5 nm in size.