Permanent, removable tissue markings

• US 6,881,249 B2
• Filed: 03/14/2003
• Issued: 04/19/2005
• Est. Priority Date: 11/20/1998
• Status: Expired due to Fees

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Freedom-2, Inc., The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Mlynarczyk, Susanna K., Anderson, Richard R., Drill, Craig A.
• Primary Examiner(s): Klemanski, Helene
• Application Number:
  US10/387,404
• Publication Number:
  US 20030159615A1
• Time in Patent Office: 767 Days
• Field of Search: 106/31.03, 106/31.15, 106/31.32, 106/31.33, 106/31.64, 106/31.65, 428/403, 424/98, 424/490, 424/9.8
• US Class Current: 106/31.03
• 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 colored microparticle comprising

(i) an indispersible, biologically inert coating comprising from about 10 to about 95 percent of the volume of the microparticle,

(ii) a core enveloped within the coating, wherein the core comprises a chromophore that is detectable through the coating and is dispersible in living tissue upon release from the microparticle, and

(iii) a discrete absorption component that absorbs a specific energy and that is located in the coating or the core, or both;

wherein the absorption component ruptures the microparticle when exposed to the specific energy, releasing the chromophore which disperses in the living tissue.

2. The colored microparticle of claim 1, wherein the microparticle has a radius of from 50 nanometers to 100 microns.

3. The colored microparticle of claim 1, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or any combination thereof.

4. The colored microparticle of claim 1, wherein the specific energy is infrared or near-infrared radiation.

5. The colored microparticle of claim 1, wherein the absorption component forms a plug sealing a hole in the coating, wherein the plug is destroyed upon exposure to the specific energy to open the hole in the coating.

6. The colored microparticle of claim 1, wherein one or more absorption components are located within the coating, and when exposed to the specific energy cause the coating to break open.

7. The colored microparticle of claim 1, wherein the microparticle is sterilized.

8. A tissue marking ink comprising the colored microparticle of claim 1 and a liquid carrier.

9. The ink of claim 8, wherein the carrier comprises alcohol, water, or glycerin, or any combination thereof.

10. A colored microparticle comprising

(i) an indispersible, biologically inert coating comprising from about 10 to about 95 percent of the volume of the microparticle,

(ii) a core enveloped within the coating, wherein the core comprises a chromophore that is detectable through the coating and is altered upon exposure of the microparticle to a specific energy, and

(iii) a discrete absorption component that absorbs the specific energy and that is located in the coating or the core, or both;

wherein the absorption component alters the chromophore when exposed to the specific energy.

11. The colored microparticle of claim 10, wherein the microparticle has a radius of from 50 nanometers to 100 microns.

12. The colored microparticle of claim 10, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, or any combination thereof.

13. The colored microparticle of claim 10, wherein the specific energy is infrared or near-infrared radiation.

14. The colored microparticle of claim 10, wherein the specific energy is ultraviolet or high-intensity visible radiation.

15. The colored microparticle of claim 10, wherein the microparticle is sterilized.

16. The colored microparticle of claim 10, further comprising a sub-microparticle, wherein the sub-microparticle comprises a bleaching agent and a discrete absorption component that causes the bleaching agent to be released from the sub-microparticle upon exposure of the microparticle to the specific energy, thereby bleaching the chromophore.

17. The colored microparticle of claim 16, wherein the bleaching agent comprises a peroxide, hypochlorite, excited oxygen species, or free radical.

18. The colored microparticle of claim 16, wherein the chromophore is pH-sensitive, and the bleaching agent is an acid, a base, or a buffer capable of effecting a pH transition that bleaches the chromophore.

19. A tissue marking ink comprising the colored microparticle of claim 10 and a liquid carrier.

20. The ink of claim 19, wherein the carrier comprises alcohol, water, glycerin, or any combination thereof.

29. The colored microparticle of claim 16, wherein the sub-microparticle comprises a coating, and the discrete absorption component is located in the bleaching agent or the coating, or both.

21. A colored microparticle comprising:

(i) a biologically inert coating having a thickness of from 0.05 to 0.6 times the radius of the microparticle,

(ii) a core enveloped within the coating, wherein the core comprises a chromophore which is detectable through the coating and is dispersible in living tissue upon release from the microparticle,

wherein the microparticle ruptures upon exposure to a specific energy.

22. The colored microparticle of claim 21, wherein the microparticle has a radius of from 50 nanometers to 100 microns.

23. The colored microparticle of claim 21, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or any combination hereof.

24. The colored microparticle of claim 21, wherein the specific energy is infrared or near-infrared radiation.

25. The colored microparticle of claim 21, wherein the coating further comprises an absorption component.

26. The colored microparticle of claim 25, wherein the absorption component forms a plug sealing an opening in the coating, wherein the opening is unsealed upon exposure to the specific energy.

27. A tissue marking ink comprising the colored microparticle of claim 21 and a liquid carrier.

28. The ink of claim 27, wherein the carrier comprises at least one of alcohol, water, or glycerin.

30. A tissue marking particle comprising a chromophore encapsulated by a biologically inert coating, the chromophore being dispersible within tissue, wherein the chromophore has an average particle size of less than about 50 nm.

31. The particle of claim 30, wherein the particle absorbs a specific energy.

32. The particle of claim 31, wherein the coating absorbs a specific energy.

33. The particle of claim 31, wherein the chromophore absorbs specific energy.

34. The particle of claim 33, wherein the chromophore is thermochemically reactive and the specific energy is heat energy.

35. The particle of claim 30, wherein the chromophore is soluble in bodily fluids within the tissue.

36. The particle of claim 30, wherein the chromophore is capable of being metabolized in the tissue.

37. The particle of claim 30, wherein the coating is ruptured when exposed to a specific energy.

38. The particle of claim 30, wherein the chromophore is selected from the group consisting of rifampin, β

-carotene, tetracycline, indocyanine green, Evan'"'"'s blue, methylene blue, Brilliant Blue FCF, Fast Green FCF, Erythrosine, Allura Red AC, Tartrazine, and Sunset Yellow FCF.

39. The particle of claim 31, wherein the specific energy is near-infrared or infrared radiation.

40. The particle of claim 32, wherein the specific energy is near-infrared or infrared radiation.

41. The particle of claim 33, wherein the specific energy is near-infrared or infrared radiation.

42. The particle of claim 30, wherein the coating comprises at least one of a metal oxide, silica, glass, fluorocarbon resin, organic polymer, or wax.

43. The particle of claim 30, wherein the coating is substantially visibly transparent and absorbs near-infrared radiation at a wavelength within the range of from 750 nm to 2000 nm.

44. The particle of claim 30, wherein the coating comprises pores of a size sufficient to allow the dispersible chromophore to leach out of the particle.

45. The particle of claim 30, wherein the particle further comprises a discrete absorption component selected from the group consisting of Schott filter glass, graphite, carbon, a metal oxide, an acrylate polymer, and a urethane polymer.