Permanent, removable tissue markings

• US 6,814,760 B2
• Filed: 01/10/2003
• Issued: 11/09/2004
• 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: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Mlynarczyk, Susanna K., Anderson, Richard R., Drill, Craig A.
• Primary Examiner(s): EINSMANN, MARGARET V
• Application Number:
  US10/340,407
• Publication Number:
  US 20030113540A1
• Time in Patent Office: 669 Days
• Field of Search: 810/4, 106/31.03, 106/31.15, 106/31.32, 106/31.33, 106/31.64, 106/31.65, 428/403
• US Class Current: 8/404
• 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 method of applying to a tissue a detectable marking that can be changed or removed, or both, on demand, the method comprising:

obtaining colored microparticles each comprising a chromophore and a discrete absorotion component that alters the microparticle when exposed to a specific energy; and

implanting into the tissue a sufficient number of the colored microparticles to form a detectable tissue marking, wherein the tissue marking is permanent until the specific energy is applied to alter a sufficient number of the microparticles to change or remove, or both, the detectable marking.

2. The method of claim 1, wherein the specific energy is electromagnetic radiation.

3. The method of claim 1, wherein the specific energy is applied once to change or remove, or both, the detectable marking.

4. A method of claim 1, wherein

(a) the colored microparticles each further comprise

(i) an indispersible, biologically inert coating, and

(ii) a core enveloped within the coating, wherein the core comprises the chromophore which is detectable through the coating and is dispersible in the tissue upon release from the microparticle, wherein the discrete absorption component is located in the coating or the core, or both.

5. The method of claim 4, wherein the dispersible chromophore is dissolved when released into the tissue.

6. The method of claim 4, wherein the dispersible chromophore is metabolized when released into the tissue.

7. The method of claim 4, wherein the chromophore is insoluble and has a size and configuration such that it is physically relocated from the detectable marking by biological processes when released into the tissue.

8. The method 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), and FD&

C Yellow No. 6 (Sunset Yellow FCF).

9. The method of claim 1, wherein the chromophore is a colored substance approved by the United States Food and Drug Administration for use in humans.

10. The method of claim 1, wherein the chromophore can be detected by the naked eye under normal lighting conditions.

11. The method of claim 1, wherein the chromophore can be detected when exposed to ultraviolet, near-ultraviolet, infrared, or near-infrared radiation.

12. The method of claim 4, wherein the coating, the chromophore, or the discrete absorption component, or any combination thereof, absorbs specific electromagnetic radiation.

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

14. The method of claim 4, wherein the coating comprises a metal oxide, silica, glass, fluorocarbon resin, organic polymer, wax, or a combination thereof.

15. The method of claim 4, wherein the coating is substantially visibly transparent and absorbs near-infrared radiation.

16. The method of claim 4, wherein the absorption component is selected from the group consisting of Schott filter glass graphite, carbon, a metal oxide, an acrylate polymer, or a urethane polymer.

17. The method of claim 4, wherein the coating comprises an absorption component that absorbs near-infrared radiation.

18. The method of claim 15, wherein the coating is comprised of a material that absorbs the near-infrared radiation.

19. The method of claim 4, wherein the coating comprises pores of a size sufficient to allow the dispersible chromophore to leach out of the microparticle.

20. The method of claim 4, wherein multiple cores are enveloped within the coating of a single microparticle.

21. The method of claim 1, wherein the tissue is selected from the group consisting of skin, iris, sclera, dentin, fingernails, toenails, tissue beneath fingernails, tissue beneath toenails, tissue inside the mouth, or tissue lining internal body passages.

22. A methode of changing or removing, or both, a detectable marking created by implanting into tissue a sufficient number of colored microparticles each comprising a chromophore and a discrete absorption component that alters the microparticle when exposed to a specific energy, the methode comprising:

exposing the detectable marking to the specific energy for a time sufficient to alter a sufficient number of the microparticles, thereby changing or removing, or both, the detectable tissue marking.

23. The methode of claim 22, wherein the specific energy is electromagnetic radiation.

24. The methode of claim 22, wherein

(a) the colored microparticles each further comprise

(i) an indispersible, biologically inert coating, and

(ii) a core enveloped within the coating, wherein the core comprises the chromophore which is detectable through the coating and is dispersible in the tissue upon release from the microparticle, wherein the discrete absorption component is located in the coating or the core, or both.

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

26. The method of claim 22, wherein the specific energy is applied at a wavelength, at an intensity, or for a duration, or any combination thereof, insufficient to completely remove or change the detectable marking, thereby partially removing or changing, or both, the detectable marking.

27. The method of claim 22, wherein the specific energy is near-ultraviolet or high-intensity visible radiation.

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

selecting microparticles comprising a chromophore encapsulated by a biologically inert coating, the chromophore being dispersible within the tissue, wherein the chromophore has an average particle size of less than about 50 nm; and

implanting into the tissue a sufficient quantity of the microparticles to form a visually detectable marking in the tissue, the chromophore being isolated from the tissue by the coating.

29. The method of claim 28, wherein the chromophore is placed in contact with the tissue following exposure of the microparticle to specific energy after implantation.

30. The method of claim 29, wherein the microparticle absorbs the specific energy.

31. The method of claim 29, wherein the chromophore absorbs the specific energy.

32. The method of claim 29, wherein the coating absorbs the specific energy.

33. The method according to claim 31, wherein the chromophore is thermochemically reactive and the specific energy is heat energy.

34. The method of claim 29, wherein the chromophore is soluble in bodily fluids within the tissue.

35. The method of claim 28, wherein the chromophore is metabolized in the tissue.

36. The method of claim 29, wherein the coating is ruptured upon exposure to said specific energy.

37. The method of claim 29, 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.

38. The method of claim 28, wherein the chromophore can be detected by the naked eye under normal daylight lighting conditions.

39. The method of claim 28, wherein the chromophore can be detected under ultraviolet, near-ultraviolet, infrared, or near-infrared radiation.

40. The method of claim 29, wherein the specific energy is near-infrared or infrared radiation.

41. The method of claim 29, wherein the coating comprises at least one of a metal oxide, silica, glass, fluorocarbon resin, organic polymer, or wax.

42. The method of claim 28, wherein the coating is substantially visibly transparent and strongly absorbs near-infrared radiation at a wavelength within the range of from 750 nm to 2000 nm.

43. The method of claim 28, wherein the coating comprises pores of a size sufficient to allow the dispersible chromophore to leach out of the microparticle.

44. The method of claim 28, wherein the microparticle 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.

45. A method of changing a detectable marking created by the process of claim 28, the method comprising:

exposing the detectable mark to specific energy.

46. A method of applying to a tissue a detectable marking that can be changed or removed, or both, on demand, the method comprising:

obtaining colored microparticles, each microparticle comprising a plurality of sub-microparticles encapsulated within an indipersible, biologically inert first coating, each sub-microparticle comprising;

(i) a second coating, and

(ii) a core enveloped within the second coating, the core comprising a chromophore which is detectable through the first and second coatings; and

implanting into the tissue a sufficient number of the colored microparticles to form a detectable tissue marking, wherein the tissue marking is permanent until a specific energy is applied to alter the microparticles to change or remove, or both, the detectable marking.

47. A method of changing or removing, or both, a detectable marking created by implanting into tissue a sufficient number of colored microparticles, each microparticle comprising a plurality of sub-microparticles encapsulated within an indispersible, biologically inert first coating, each sub-microparticle comprising:

(i) a second coating, and

(ii) a core enveloped within the second coating, the core comprising a chromophore which is detectable through the first and second coatings, the method comprising;

exposing the detectable marking to a specific energy for a time sufficient to alter a sufficient number of the microparticles, thereby changing or removing, or both, the detectable tissue marking.