Permanent, removable tissue markings

• US 7,435,524 B2
• Filed: 10/22/2007
• Issued: 10/14/2008
• Est. Priority Date: 11/20/1998
• Status: Expired due to Fees

• Current Assignee: Craig A. Drill, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Freedom-2, Inc., General Hospital Corporation
• Inventors: Anderson, Richard Rox, Drill, Craig A., Mlynarczyk-Evans, Susanna K.
• Primary Examiner(s): Walke; Amanda C.
• Application Number:
  US11/876,410
• Publication Number:
  US 20080044746A1
• Time in Patent Office: 358 Days
• Field of Search: 430/138, 430/139, 430/944, 430/964, 106/31.03, 840/4, 428/403
• US Class Current: 430/138
• 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

The present invention provides microparticles that create permanent tissue markings, such as tattoos, designed in advance for change and/or removal on demand, as well as methods for implanting the microparticles in tissue and changing and/or removing the resulting markings. Colored microparticles are constructed with specific electromagnetic absorption and/or structural properties that facilitate changing and/or removing tissue markings made using the microparticles by applying specific energy (such as electromagnetic radiation from a laser or flash-lamp) to the tissue marking site.

Claims

1. A tissue marking ink comprising:

a particle comprising a thermolabile chromophore that becomes invisible upon heating by application of a specific energy; and

a carrier.

2. The ink of claim 1, wherein the particle further comprises a component in contact with the chromophore that indirectly heats the chromophore upon application of the specific energy.

3. The ink of claim 1, wherein the particle further comprises a thermally initiated activator mixed into the chromophore that releases free radicals upon heating by application of the specific energy.

4. The ink of claim 1, wherein the specific energy is electromagnetic radiation.

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

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

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

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

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

an indispersible, biologically inert coating; and

a core enveloped within the coating, wherein the core comprises the chromophore.

10. The ink of claim 9, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or a combination thereof.

11. The ink of claim 9, wherein the coating is substantially visibly transparent and absorbs near-infrared radiation.

12. The ink of claim 9, wherein multiple cores are enveloped within the coating of a single particle.

13. The ink of claim 9, wherein the chromophore is detectable through the coating.

14. The ink of claim 9, wherein the coating comprises from about 10 to about 95 percent of the volume of the particle.

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

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

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

18. The ink of claim 1, wherein the particle is less than about 5 nm in size.

19. The ink of claim 1, wherein the carrier comprises at least one of alcohol, water, or glycerin.

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

providing the tissue marking ink of claim 1; and

implanting said ink into a tissue to form a tissue marking,

wherein the chromophore becomes invisible upon exposure to a specific energy when the ink is within the tissue.

21. The method of claim 20, wherein the specific energy is electromagnetic radiation.

22. The method of claim 20, wherein the specific energy is infrared or near-infrared radiation.

23. A method for altering a tissue marking implanted in tissue, wherein the tissue marking comprises the ink of claim 1, wherein the chromophore that becomes invisible upon heating by application of a specific energy when the ink is within the tissue, the method comprising exposing the tissue marking to the specific energy for a sufficient time to render the chromophore substantially invisible.

24. The method of claim 23, wherein the specific energy is electromagnetic radiation.

25. The method of claim 23, wherein the specific energy is infrared or near-infrared radiation.

26. A tissue marking ink comprising a particle, wherein the particle comprises polymethylmethacrylate (PMMA) and an iron oxide absorption component, wherein the particle ruptures upon exposure to a specific energy when the particle is within a tissue.

27. The tissue marking ink of claim 26, further comprising a chromophore.

28. The tissue marking ink of claim 27, wherein the chromophore is a Food and Drug Administration (FDA)-approved dye.

29. The tissue marking ink of claim 27, wherein the chromophore is selected from the group consisting of phthalocyanine dyes, cyanine dyes, and pyrylium dyes.

30. The tissue marking ink of claim 27, wherein the chromophore is carbon black.

31. The tissue marking ink of claim 27, wherein the chromophore is selected from the group consisting of rifampin, β

-carotene, tetracycline, indocyanine green, Evan'"'"'s blue, and methylene blue.

32. The tissue marking ink of claim 27, wherein the chromophore is selected from the group consisting of FD&

C Blue No. 2, 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 (ALLURA™

Red AC), FD&

C Yellow No. 5 (Tartrazine), and FD&

C Yellow No. 6 (Sunset Yellow FCF).

33. The tissue marking ink of claim 27, wherein the chromophore is a soluble inorganic salt selected from the group consisting of copper sulfate, Cu(NH₃)²⁺, MnO₄, NiCl₂, CrO₄, and Cr₂O₇²⁻

.

34. The tissue marking ink of claim 27, wherein the chromophore is white.

35. The tissue marking ink of claim 27, wherein the chromophore is yellow.

36. The tissue marking ink of claim 27, wherein the chromophore is blue.

37. The tissue marking ink of claim 27, wherein the chromophore is green.

38. The tissue marking ink of claim 27, wherein the chromophore is red.

39. The tissue marking ink of claim 26, wherein the particle is less than about 5 microns in diameter.

40. The tissue marking ink of claim 26, wherein the particle is in the nanometer size range.

41. The tissue marking ink of claim 26, wherein the particle is suspended in a liquid carrier.

42. The tissue marking ink of claim 41, wherein the carrier comprises alcohol, water, or glycerin, or any combination thereof.

43. The tissue marking ink of claim 26, wherein the specific energy is laser radiation.

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

providing the tissue marking ink of claim 26; and

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

45. A method for rendering undetectable a tissue marking implanted in tissue, the tissue marking comprising a particle comprising polymethylmethacrylate (PMMA), an iron oxide absorption component, and a chromophore, wherein the particle is rendered undetectable upon exposure to a specific energy when the particle is within a tissue, the method comprising exposing the tissue marking to the specific energy for a sufficient time to render the particle undetectable.

46. The method of claim 45, wherein the specific energy is laser radiation.