Systems and methods for interior energy-activation from an exterior source

• US 9,682,250 B2
• Filed: 08/02/2016
• Issued: 06/20/2017
• Est. Priority Date: 04/08/2007
• Status: Active Grant

• Current Assignee: Immunolight, LLC
• Original Assignee: Immunolight, LLC
• Inventors: Bourke, Jr., Frederic A.
• Primary Examiner(s): MCCLENDON, SANZA L
• Application Number:
  US15/226,567
• Publication Number:
  US 20160354467A1
• Time in Patent Office: 322 Days
• CPC Class Codes: A23L 2/50 by irradiation or electric treatment without heating
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• CPC Class Codes: A61K 41/0066 Psoralene-activated UV-A photochemotherapy (PUVA-therapy), e.g. for treatment of psoriasis or eczema, extracorporeal photopheresis with psoralens or fucocoumarins
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• CPC Class Codes: A61L 2/10 Ultraviolet radiation
• CPC Class Codes: A61L 2/16 using chemical substances
• CPC Class Codes: A61L 2202/21 Pharmaceuticals, e.g. medicaments, artificial body parts
• CPC Class Codes: A61L 2202/22 Blood or products thereof
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Abstract

A method and a system for producing a change in a medium. The method places in a vicinity of the medium at least one energy modulation agent. The method applies an initiation energy to the medium. The initiation energy interacts with the energy modulation agent to directly or indirectly produce the change in the medium. The system includes an initiation energy source configured to apply an initiation energy to the medium to activate the energy modulation agent.

Claims

1. A method for treating a condition, disorder or disease comprising:

generating an activation energy in-situ in a subject; and

prior to or simultaneously with generating the activation energy, administering to the subject at least one activatable pharmaceutical agent that is activatable in situ by the activation energy, wherein upon activation, the activated at least one activatable pharmaceutical agent reacts with a target cell in the subject, which causes an auto-vaccine effect in the subject, thereby treating the condition, disorder, or disease.

2. The method of claim 1, wherein the activation energy is generated in-situ in said subject by application of an initiation energy which is converted in-situ to said activation energy.

3. The method of claim 2, wherein the initiation energy is at least one member selected from the group consisting of x-rays, gamma rays, electron beams;

and protons.

4. The method of claim 1, wherein the activation energy is generated by a source of chemical energy that provides at least one member selected from the group consisting of chemiluminescence, phosphorescence, and bioluminescence.

5. The method of claim 2, further comprising, prior to said applying of the initiation energy, administering to the subject at least one energy modulation agent that assists in converting the initiation energy to the activation energy.

6. The method of claim 5, wherein the at least one energy modulation agent comprises one or more selected from a biocompatible fluorescing metal nanoparticle, fluorescing dye molecule, gold nanoparticle, a ater soluble quantum dot encapsulated by polyamidoamine dendrimers, a luciferase, a biocompatible phosphorescent molecule, a combined electromagnetic energy harvester molecule, and a lanthanide chelate capable of intense luminescence.

7. The method of claim 5, wherein the energy modulation agent comprises a fluorophore.

8. The method of claim 5, wherein the at least one energy modulation agent comprises a single energy modulation agent, and is coupled to said at least one activatable pharmaceutical agent.

9. The method of claim 3, wherein the initiation energy is selected from the group consisting of x-rays and electron beams.

10. The method of claim 2, wherein the initiation energy produces energy states for energy transfer to the at least one activatable pharmaceutical agent.

11. The method of claim 1, wherein the activation energy is generated in a solid tumor.

12. The method of claim 2, wherein the initiation energy directly or indirectly activates the at least one activatable pharmaceutical agent.

13. The method of claim 12, wherein the at least one activatable pharmaceutical agent is at least one psoralen compound.

14. The method of claim 13, wherein at least one psoralen compound is at least one member selected from the group consisting of psoralen, 8-MOP and AMT.

15. The method of claim 2, wherein the initiation energy damages DNA in target cells.

16. The method of claim 2, wherein the initiation energy comprises ionizing radiation which interacts to produce reactive groups at a target site.

17. The method of claim 16, wherein the reactive groups comprise at least a member selected from the group consisting of ions, singlet oxygen, free radicals, and hydroxides.

18. The method of claim 1, wherein the at least one activatable pharmaceutical agent is activated by one or more sequential single photon absorption events.

19. The method of claim 1, wherein the at least one activatable pharmaceutical agent comprises an active agent contained within a photocage, and said activation energy is UV-A or visible energy, wherein upon exposure to said UV-A or visible energy, the photocage disassociates from the active agent, rendering the active agent available.

20. The method of claim 1, wherein the activation energy is capable of penetrating human tissue up to about 4 mm.

21. The method of claim 1, wherein the disorder is at least one member selected from the group consisting of cancer, bacterial infection, viral infection, immune rejection response, autoimmune disorders, and aplastic conditions.

22. The method of claim 1, wherein the at least one activatable pharmaceutical agent is a photoactivatable agent.

23. The method of claim 1, wherein the at least one activatable pharmaceutical agent is selected from the group consisting of psoralens, pyrene cholesteryloleate, acridine, porphyrin, fluorescein, rhodamine, 16-diazorcortisone, ethidium, transition metal complexes of bleomycin, transition metal complexes of deglycobleomycin organoplatinum complexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites, vitamin precursors, naphthoquinones, naphthalenes, naphthols and derivatives thereof having planar molecular conformations, porphyrins, dyes and phenothiazine derivatives, coumarins, quinolones, quinones, and anthroquinones.

24. The method of claim 1, wherein the at least one activatable pharmaceutical agent is a psoralen, a coumarin, or a derivative thereof.

25. The method of claim 24, wherein the at least one activatable pharmaceutical agent is 8-MOP or AMT.

26. The method of claim 1, wherein the at least one activatable pharmaceutical agent is one selected from 7,8-dimethyl-10-ribityl, isoalloxazine, 7,8,10-trimethylisoalloxazine, 7,8-dimethylalloxazine, isoalloxazine-adenine dinucleotide, alloxazine mononucleotide, aluminum (III) phthalocyanine tetrasulfonate, hematoporphyrin, and phthalocyanine.

27. The method of claim 1, wherein the at least one activatable pharmaceutical agent is coupled to a carrier that is capable of binding to a receptor site.

28. The method of claim 27, wherein the carrier is one selected from insulin, interleukin, thymopoietin or transferrin.

29. The method of claim 28, wherein the at least one activatable pharmaceutical agent is coupled to the carrier by a covalent bond.

30. The method of claim 28, wherein the at least one activatable pharmaceutical agent is coupled to the carrier by a non-covalent bond.

31. The method of claim 28, wherein the receptor site is one selected from nucleic acids of nucleated cells, antigenic sites on nucleated cells, or epitopes.

32. The method of claim 1, wherein the at least one activatable pharmaceutical agent has affinity for a target cell.

33. The method of claim 1, wherein the at least one activatable pharmaceutical agent is capable of being preferentially absorbed by a target cell.

34. The method of claim 1, wherein the at least one activatable pharmaceutical agent is a DNA intercalator or a halogenated derivative thereof.

35. The method of claim 1, further comprising providing to the subject at least one additive having a complementary therapeutic or diagnostic effect.

36. The method of claim 35, wherein said additive comprises at least one of an antioxidant, an adjuvant, or a combination thereof.