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

Patent metadata

Field	Value
Publication number	US-12226483-B2
Application number	US-202117538770-A
Country	US
Kind code	B2
Filing date	Nov 30, 2021
Priority date	Feb 2, 2016
Publication date	Feb 18, 2025
Grant date	Feb 18, 2025

Abstract

A method for treating a disease in a subject in need thereof is provided involving infusing 8-methoxypsoralen (8-MOP) and a phosphor-containing drug activator into a diseased site in the subject; and delivering a dose of x-rays to the subject for production of the ultraviolet and visible light inside the subject to activate the photoactivatable drug and induce a persistent therapeutic response, the dose including a pulsed sequence of x-rays delivering from 0.5-2 Gy to the tumor, wherein the phosphor-containing drug activator includes an admixture of two or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays; the two or more phosphors including 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; wherein each of the two or more phosphors have at least one coating selected from an ethyl cellulose coating or a diamond-like carbon coating.

First claim

The invention claimed is:

1. A method for treating a tumor in a subject in need thereof, comprising:
infusing 8-methoxypsoralen (8-MOP) and a phosphor-containing drug activator into the tumor in the subject; and
delivering a dose of x-rays to the subject for production of ultraviolet and visible light inside the subject to activate the 8-methoxypsoralen (8-MOP) and induce a persistent therapeutic response, said dose comprising a pulsed sequence of x-rays delivering from 0.5-2 Gy to the tumor,
wherein the phosphor-containing drug activator comprises an admixture of two or more phosphors capable of emitting the 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; wherein each of said two or more phosphors have at least one coating selected from the group consisting of an ethyl cellulose coating and a diamond-like carbon coating.

2. The method of claim 1 , wherein infusing comprises infusing the 8-methoxypsoralen (8-MOP) untethered from the two or more phosphors.

3. The method of claim 1 , wherein infusing comprises administering the 8-methoxypsoralen (8-MOP) in accordance with a volume of the diseased site.

4. The method of claim 1 , wherein
an amount of the phosphors in the pharmaceutical carrier ranges from 0.1 to 0.66 milligrams of phosphor per cm 3 of the volume of the diseased site, and
a concentration of the 8-methoxypsoralen (8-MOP) in the pharmaceutical carrier ranges from 10 μg/mL to 50 μg/mL.

5. The method of claim 1 , wherein delivering comprises generating x-rays from a peak applied cathode voltage at or below 300 kVp.

6. The method of claim 1 , wherein delivering comprises providing a dose of x-rays in an amount to cause an auto-vaccine effect in the human or animal body.

7. The method of claim 1 , wherein delivering comprises providing one or more booster treatments which repeats the infusing and delivering steps to the tumor in the subject, wherein, in the one or more booster treatments, at least one of phosphor concentration, 8-methoxypsoralen (8-MOP) concentration, and the radiation dose is increased by a factor of at least two times respective initial values.

8. The method of claim 7 , wherein the booster treatment produces psoralen-modified cancer cells or X-ray modified cancer cells.

9. The method of claim 7 , wherein the booster treatment produces radiation damaged cancer cells.

10. The method of claim 7 , wherein a period between booster treatments is delayed according to a tolerance level of the human or animal body for radiation-modified cells generated during the booster treatment.

11. The method of claim 1 , wherein delivering comprises directing x-rays to at least one of a tumor or a malignancy.

12. The method of claim 1 , wherein delivering comprises directing x-rays to at least one of a eukaryotic cell, a prokaryotic cell, a subcellular structure, an extracellular structure, a virus or prion, a cellular tissue, a cell membrane, a nuclear membrane, cell nucleus, nucleic acid, mitochondria, ribosome, or other cellular organelle.

13. The method of claim 1 , wherein delivering comprises directing x-rays to a diseased site in a pulsed manner having an on and off time.

14. The method of claim 13 , wherein delivering comprises directing x-rays to the diseased site such that the on time activates the phosphor and the off time is long enough for decay of phosphor light emission.

15. The method of claim 1 , wherein delivering comprises directing x-rays to the tumor in a pulsed manner having an on and off time.

16. The method of claim 15 , wherein delivering comprises directing x-rays to the tumor such that the on time activates the phosphor and the off time is long enough for decay of phosphor light emission.

17. The method of claim 1 , wherein delivering comprises providing a dose of about 1Gy using twenty one x-ray pulses spaced apart by 10 seconds; and, each x-ray pulse of 800 ms is delivered from an x-ray source set at a voltage of 80 kV and an amperage of 200 mA.

18. The method of claim 7 , wherein delivering comprises providing one or more booster treatments which repeats the infusing and delivering steps to the tumor in the subject, wherein, in the one or more booster treatments, at least one of phosphor concentration, 8-methoxypsoralen (8-MOP) concentration, and the radiation dose is increased by a factor of at least five times respective initial values.

19. The method of claim 18 , wherein delivering comprises providing one or more booster treatments which repeats the infusing and delivering steps to the tumor in the subject, wherein, in the one or more booster treatments, at least one of phosphor concentration, 8-methoxypsoralen (8-MOP) concentration, and the radiation dose is increased by a factor of at least ten times respective initial values.

Assignees

• Immunolight Llc
• Univ Duke

Inventors

• Walder Harold
• Bourke Jr Frederic A
• Fathi Zakaryae
• Beyer Wayne F
• 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

• A61N2005/0661

  ultraviolet · CPC title