Phosphor-containing drug activator, suspension thereof, system containing the suspension, and methods for use

Patent metadata

Field	Value
Publication number	US-11260129-B2
Application number	US-201716074707-A
Country	US
Kind code	B2
Filing date	Feb 2, 2017
Priority date	Feb 2, 2016
Publication date	Mar 1, 2022
Grant date	Mar 1, 2022

Abstract

A phosphor-containing drug activator and suspension thereof are provided. The suspension at least includes two or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays. The two or more phosphors include Zn2SiO4:M12+ and (3Ca3 (PO4)2Ca(F, Cl)2:Sb3*, Mn2+) at a ratio NP-200:GTP-4300 of from 1:10 to 10:1, and each of the two phosphors have an ethylene cellulose coating and/or a diamond-like carbon coating. The suspension further includes a pharmaceutically acceptable carrier. A system for treating a disease in a subject in need thereof includes a) the above-noted suspension, b) a photoactivatable drug containing 8-methoxypsoralen (8-MOP or UVADEX) untethered from the two or more phosphors, c) one or more devices which infuse the photoactivatable drug and the suspension including the pharmaceutically acceptable carrier into a diseased site in the subject, and d) an x-ray source which is controlled to deliver a dose of x-rays to the subject for production of the ultraviolet light.

First claim

The invention claimed is:

1. A phosphor-containing drug activator, comprising:
an admixture of two or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays;
said two or more phosphors comprising Zn 2 SiO 4 :Mn 2+ and (3Ca 3 (PO 4 ) 2 Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) at a ratio (Zn 2 SiO 4 :Mn 2+ ):(3Ca 3 (PO 4 ) 2 Ca(F, Cl) 2 : Sb 3+ , Mn 2+ )) of from 1:10 to 10:1;
each of said two phosphors having at least one coating selected from the group consisting of an ethyl cellulose coating and a diamond-like carbon coating.

2. The phosphor-containing drug activator of claim 1 , wherein said ratio ranges from 1:5 to 5:1.

3. The phosphor-containing drug activator of claim 1 , wherein said ratio ranges from 1:2 to 2:1.

4. The phosphor-containing drug activator of claim 1 , wherein said ratio is about 1:2.

5. The phosphor-containing drug activator of claim 1 , wherein said two or more phosphors have a composition that emits said ultraviolet and visible light at wavelengths which activate 8-methoxypsoralen (8-MOP).

6. The phosphor-containing drug activator of claim 1 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has cathodoluminescent emission peaks at 160 nm, 360 nm, and 525 nm.

7. The phosphor-containing drug activator of claim 1 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a cathodoluminescent emission edge at 400 nm and a cathodoluminescent emission peaks at 570 nm.

8. The phosphor-containing drug activator of claim 1 , wherein each of said two or more phosphors has a first coating comprising said ethyl cellulose coating on the phosphor, and a second outer coating comprising said diamond-like carbon coating on said first coating.

9. The phosphor-containing drug activator of claim 1 , wherein each of said two or more phosphors has an outer coating of said ethyl cellulose coating.

10. The phosphor-containing drug activator of claim 1 , wherein each of said two or more phosphors has an outer coating of said diamond-like carbon coating.

11. The phosphor-containing drug activator of claim 1 wherein said ethyl cellulose coating is present and has a thickness between 10 and 100 nm.

12. The phosphor-containing drug activator of claim 1 , wherein said ethyl cellulose coating is present and has a thickness between 30 and 60 nm.

13. The phosphor-containing drug activator of claim 1 , wherein said diamond-like carbon coating is present and has a thickness between 50 and 200 nm.

14. The phosphor-containing drug activator of claim 1 , wherein said diamond-like carbon coating is present and has a thickness between 75 and 125 nm.

15. The phosphor-containing drug activator of claim 1 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.05 and 100 microns.

16. The phosphor-containing drug activator of claim 1 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.1 and 50 microns.

17. The phosphor-containing drug activator of claim 1 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.5 and 20 microns.

18. The phosphor-containing drug activator of claim 1 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.05 and 100 microns.

19. The phosphor-containing drug activator of claim 1 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.1 and 50 microns.

20. The phosphor-containing drug activator of claim 1 , wherein said ( 3 Ca 3 (PO 4 ) 2 Ca(F, Cl) 2 : Sb 3 +, Mn 2 +) phosphor has a size between 0.5 and 20 microns.

21. The phosphor-containing drug activator of claim 1 , wherein the diamond-like carbon coating is present and has a water-droplet contact angle between about 90 and 110°.

22. A suspension of a phosphor-containing drug activator, comprising:
two or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays;
said two or more phosphors comprising Zn 2 SiO 4 :Mn 2+ and (3Ca 3 (PO 4 ) 2 Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) at a ratio (Zn 2 SiO 4 :Mn 2+ ):(3Ca 3 (PO 4 ) 2 Ca(F, Cl) 2 : Sb 3+ , Mn 2+ )) of from 1:10 to 10:1;
each of said two phosphors having at least one coating selected from the group consisting of an ethyl cellulose coating and a diamond-like carbon coating; and
a pharmaceutically acceptable carrier.

23. The suspension of claim 22 , wherein said ratio ranges from 1:5 to 5:1.

24. The suspension of claim 22 , wherein said ratio ranges from 1:2 to 2:1.

25. The suspension of claim 22 , wherein said ratio is about 1:2.

26. The suspension of claim 22 , further comprising 8-methoxypsoralen (8-MOP).

27. The suspension of claim 22 , wherein said two or more phosphors have a composition that emits said ultraviolet and visible light at wavelengths which activate 8-methoxypsoralen (8-MOP).

28. The suspension of claim 22 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has cathodoluminescent emission peaks at 160 nm, 360 nm, and 525 nm.

29. The suspension of claim 22 , wherein said (3Ca 3 (PO 4 )2Ca(F, C 1 ) 2 : Sb 3+ , Mn 2+ ) phosphor has a cathodoluminescent emission edge at 400 nm and a cathodoluminescent emission peaks at 570 nm.

30. The suspension of claim 22 , wherein each of said two or more phosphors has a first coating comprising said ethyl cellulose coating on the phosphor, and a second outer coating comprising said diamond-like carbon coating on said first coating.

31. The suspension of claim 22 , wherein each of said two or more phosphors has an outer coating of said ethyl cellulose coating.

32. The suspension of claim 22 , wherein each of said two or more phosphors has an outer coating of said diamond-like carbon coating.

33. The suspension of claim 22 , wherein said ethyl cellulose coating is present and has a thickness between 10 and 100 nm.

34. The suspension of claim 22 , wherein said ethyl cellulose coating is present and has a thickness between 30 and 60 nm.

35. The suspension of claim 22 , wherein said diamond-like carbon coating is present and has a thickness between 50 and 200 nm.

36. The suspension of claim 22 , wherein said diamond-like carbon coating is present and has a thickness between 75 and 125 nm.

37. The suspension of claim 22 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.05 and 100 microns.

38. The suspension of claim 22 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.1 and 50 microns.

39. The suspension of claim 22 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.5 and 20 microns.

40. The suspension of claim 22 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.05 and 100 microns.

41. The suspension of claim 22 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.1 and 50 microns.

42. The suspension of claim 1 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.5 and 20 microns.

43. The suspension of claim 22 , wherein said two or more phosphors and the pharmaceutically acceptable carrier comprise a sterile solution.

44. The suspension of claim 43 , wherein a ratio of

Assignees

• Immunolight Llc
• Univ Duke

Inventors

• Walder Harold
• Bourke Jr Frederic A
• Fathi Zakaryae
• Beyer Wayne
• Oldham Mark
• Adamson Justus
• Nolan Michael

Classifications

• A61N2005/0662

  Visible light · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61N2005/1098

  Enhancing the effect of the particle by an injected agent or implanted device · CPC title

• A61N5/10 Primary

  X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) · CPC title