Phosphor-containing drug activator activatable by a Monte Carlo derived x-ray exposure, system containing the activator, and methods for use

Patent metadata

Field	Value
Publication number	US-10940329-B2
Application number	US-201715819130-A
Country	US
Kind code	B2
Filing date	Nov 21, 2017
Priority date	Nov 22, 2016
Publication date	Mar 9, 2021
Grant date	Mar 9, 2021

Abstract

A phosphor-containing drug activator activatable from a Monte Carlo derived x-ray exposure for treatment of a diseased site. The activator includes an admixture or suspension of one or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays, wherein a distribution of the phosphors in the diseased target site is based on a Monte Carlo derived x-ray dose. A system for treating a disease in a subject in need thereof, includes the drug activator and a photoactivatable drug, one or more devices which infuse the photoactivatable drug and the activator including the pharmaceutically acceptable carrier into a diseased site in the subject; and an x-ray source which is controlled to deliver the Monte Carlo derived x-ray exposure to the subject for production of ultraviolet and visible light inside the subject to activate the photoactivatable drug.

First claim

The invention claimed is:

1. A method for treating a disease in a subject in need thereof, comprising:
prior to treating the disease, performing a Monte Carlo calculation to ascertain an x-ray energy distribution inside a target site of the disease; and
delivering a phosphor-containing drug activator and a photoactivatable drug to the target site of the disease in a distribution within the target site as determined by the Monte Carlo calculation, wherein the phosphor-containing drug activator is activatable from the Monte Carlo calculation derived x-ray exposure for treatment of the target site of the disease,
wherein the phosphor-containing drug activator comprises:
an admixture or suspension of one or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays;
wherein a distribution of the phosphors in the diseased target site or an x-ray dose to the diseased site or both is based on the Monte Carlo calculation derived x-ray dose.

2. The method of claim 1 , wherein performing a Monte Carlo calculation comprises introducing a modeled beam of x-rays from different angular directions in order to ascertain which direction provides a dose to the target site of the disease before exceeding a maximum dose permissible in nearby bone tissue.

3. The method of claim 1 , wherein performing a Monte Carlo calculation comprises introducing a modeled beam of x-rays from different shaped beams in order to ascertain which beam shape provides a dose to the target site of the disease before exceeding a maximum dose permissible in nearby bone tissue.

4. The method of claim 1 , wherein performing a Monte Carlo calculation comprises introducing a modeled beam of x-rays from different peak beam energies in order to ascertain which peak beam energy provides a dose to the target site of the disease before exceeding a maximum dose permissible in nearby bone tissue.

5. The method of claim 1 , wherein performing a Monte Carlo calculation comprises modeling the x-ray penetration or absorbed dose distribution in the target site.

6. The method of claim 5 , wherein modeling the x-ray penetration or absorbed dose distribution in the target site comprises accommodating in the modeling a distribution of bone and soft tissue including a tumor region to be treated.

7. The method of claim 5 , wherein modeling the x-ray penetration or absorbed dose distribution in the target site comprises accommodating in the modeling a concentration profile of the one or more phosphors in the target site.

8. The method of claim 5 , wherein modeling the x-ray penetration or absorbed dose distribution in the target site comprises accommodating in the modeling a material and size of the one or more phosphors.

9. The method of claim 5 , wherein modeling the x-ray penetration or absorbed dose distribution in the target site comprises accommodating in the modeling an emitted light distribution from the one or more phosphors.

10. The method of claim 1 , wherein said one or more phosphors comprise Zn 2 SiO 4 :Mn 2+ and (3Ca 3 (PO 4 ) 2 Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) at a ratio from 1:10 to 10:1 or ratio from 1:5 to 5:1.

11. The method of claim 10 wherein said ratio ranges from 1:2 to 2:1.

12. The method of claim 10 , wherein said ratio is about 1:2.

13. The method of claim 1 , wherein said phosphors have a composition that emits said ultraviolet and visible light at wavelengths which activate 8-methoxypsoralen (8-MOP).

14. The method of claim 10 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has cathodoluminescent emission peaks at 160 nm, 360 nm, and 525 nm.

15. The method of claim 10 , wherein said (3Ca 3 (PO 4 ) 2 Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a cathodoluminescent emission edge at 400 nm and a cathodoluminescent emission peaks at 570 nm.

16. The method of claim 1 , wherein each of said one or more phosphors has a first coating comprising said ethylene cellulose coating on the phosphor, and a second outer coating comprising said diamond-like carbon coating on said first coating.

17. The method of claim 1 , wherein each of said one or more phosphors has an outer coating of said ethylene cellulose coating.

18. The method of claim 1 , wherein each of said one or more phosphors has an outer coating of said diamond-like carbon coating.

19. The method of claim 17 , wherein said ethylene cellulose coating is present and has a thickness between 10 and 100 mn.

20. The method of claim 17 , wherein said ethylene cellulose coating is present and has a thickness between 30 and 60 nm.

21. The method of claim 18 , wherein said diamond-like carbon coating is present and has a thickness between 50 and 200 nm.

22. The method of claim 18 , wherein said diamond-like carbon coating is present and has a thickness between 75 and 125 nm.

23. The method of claim 10 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.05 and 100 microns.

24. The method of claim 10 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.1 and 50 microns.

25. The method of claim 10 , wherein said Zn 2 SiO 4 :Mn 2+ phosphor has a size between 0.5 and 20 microns.

26. The method of claim 10 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.05 and 100 microns.

27. The method of claim 10 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.1 and 50 microns.

28. The method of claim 10 , wherein said (3Ca 3 (PO 4 )2Ca(F, Cl) 2 : Sb 3+ , Mn 2+ ) phosphor has a size between 0.5 and 20 microns.

29. The method of claim 1 , wherein the target site is a tumor.

30. The method of claim 2 , wherein the target site is a tumor.

31. The method of claim 3 , wherein the target site is a tumor.

32. The method of claim 4 , wherein the target site is a tumor.

33. The method of claim 7 , wherein the target site is a tumor.

Assignees

• Immunolight Llc
• Univ Duke

Inventors

• Oldham Mark
• Adamson Justus
• Yoon Paul
• Walder Harold
• Bourke Jr Frederic A
• Fathi Zakaryae
• Beyer Wayne F

Classifications

• A61K49/0423

  Nanoparticles, nanobeads, nanospheres, nanocapsules, i.e. having a size or diameter smaller than 1 micrometer · CPC title

• A61K41/0066

  Psoralene-activated UV-A photochemotherapy (PUVA-therapy), e.g. for treatment of psoriasis or eczema, extracorporeal photopheresis with psoralens or fucocoumarins · CPC title

• A61K31/37

  Coumarins, e.g. psoralen · CPC title

• C09K11/595

  with zinc or cadmium · CPC title

• A61N2005/1034

  Monte Carlo type methods; particle tracking · CPC title