Claims for Patent: 4,767,611

Summary for Patent: 4,767,611

Title:	Method for affecting intracellular and extracellular electric and magnetic dipoles
Abstract:	Described is a treatment of cancer and other disease processes, including infectious diseases through the use of external electromagnetic energy to alter electric and magnetic dipoles intracellularly to produce as in the case of cancer, death of the cancer cells in living tissue. The normal cells are not damaged. The process comprises introducing minute particles into the interior of cells in living tissue. These particles are capable of affecting the intracellular conductivity, dielectric properties, dipole content and membrane characteristics of the cell and nucleus. The particles are introduced intravenously, intra-arterially, and/or intra-lymphatically and the subject is then exposed to an alternating electromagnetic field to introduce energy into the interior of the cancer cells and thereby destroy the cancer cells without harming the normal cells. Further, selectivity may be achieved by incorporating specific radioisotopes or tumor specific antibodies bound to the particles. This treatment process may also be used to affect atherosclerotic lesions as well as other disease processes.
Inventor(s):	Gordon; Robert T. (Skokie, IL)
Assignee:
Application Number:	06/627,536
Patent Claims:	1. A process for the treatment of diseased cells in at least one region in the tissue of a host organism containing said diseased cells and living normal cells without substantially damaging said living normal cells comprising: providing to said host organism minute particles less than about 1 micron capable of being taken up by said diseased cells, allowing said particles to effect at least one event comprising intracellular events and membrane events in said tissue, subjecting said organism to relatively low frequency alternating, oscillating, or pulsed electromagnetic field to provide energy to said diseased cells and selectively heat said diseased cells wherein said particles are selected from the group consisting of: (a) cobalt, zinc, iron, chromium, nickel, platinum, rare earth metals and compounds selected from the group consisting of dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium; dysprosium sulfate, erbium sulfate, euorpium oxide, europium sulfate, gadolinium oxide, gadolinium sulfate, holmium oxide, samarium sulfate, terbium sulfate, thulium oxide, ytterbium sulfide, yttrium oxide, yttrium sulfate, yttrium ferrioxide (Y.sub.3 Fe.sub.5 O.sub.12), yttrium oxide (Y3Al.sub.5 O.sub.12), dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbrium-iron, cobalt-samarium, gadolinium-ytterbium, dysprosium-gallium, and actinide series elements and compounds thereof: (b) dextran metal complexes wherein said metal is selected from the group consisting of cobalt, zinc, chromium, iron, gallium, manganese, nickel, platinum, dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium, iron, ytterbium, iron, cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium: (c) iron transporting and chelating compounds selected from the group consisting of ferric ammonium citrate, enterochelin, transferrin, metallothionein, hydroxamates, phenolates, ferrichromes, desferriferrichromes, ferritin, ferric mycobactins, ferredoxin and rubredoxin: (d) porphyrins selected from the group consisting of etioporphyrins, meso-porphyrins, uroporphyrins, coproporphyrins, protoporphyrins, dicarboxylic acid containing porphyrins, tetraphenylporphyrin sulfonate, hematoporphyrins, chlorophylls, and cytochromes: (e) and combinations of the materials of said sub-paragraphs (a), (b), (c) and (d). 2. The process of claim 1 wherein said alternating, oscillating or pulsed electromagnetic field is between about 1 Hz to about 100 MHz. 3. The process of claim 2 wherein said alternating, oscillating or pulsed electromagnetic field is produced by apparatus comprising a coil, capacitor plates or electrode in said tissue. 4. The process of claim 1 wherein said particles are selected to affect the intracellular conductivity, dielectric properties, charge accumulation on the membrane, membrane conductance, membrane capacitance and the electric and magnetic dipole environment of said diseased cells and said normal cells. 5. The process of claim 4 for heating said diseased cells comprising selecting said particles to produce the effect of decreasing the power level at a given frequency of said field, said particles altering intracellular environment and membrane characteristics in said tissue when said particles are administered to said host. 6. The process of claim 4 for heating said diseased cells comprising selecting said particles to produced the effect of decreasing the frequency of said field, said particles altering the intracellular environment and membrane characteristics in said tissue when said particles are administered to said host. 7. The process of claim 1 wherein the natural occurring metal moiety of said porphyrin is further substituted with a metal selected form the group comprising cobalt, zinc, chromium, gallium, iron, manganese, nickel, platinum, dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, yttrebium-iron, cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium; and combinations thereof. 8. The process according to claim 1 or 7 wherein said iron transporting, iron chelating and porphyrin compounds are chemically complexed with dextran. 9. The process according to claim 8 wherein said compound is chemically complexed with an antibody. 10. The process according to claim 1 wherein said particles are selected from the group comprising Fe(III) Tetraphenylporphyrin sulfonate (TPPS.sub.4) Acetate, Fe(III) TPPS.sub.4 Acetate 4Na Salt (H.sub.2 O), Fe(III) Mesoporphyrin IX Chloride, Fe(III) TPPS.sub.4 Chloride, Co TPPS.sub.4, Co(III) MesoTPPS.sub.4 Tetra Na Salt (Acetate), Fe Phthalocyanine Tetrasulfonate Tetra sodium salt, Tetra Sodium-meso-Tetra (4-sulfonate-phenyl) Porphine (12 hydrate), Fe(III) Tetra (N-Methyl 4-Puridyl) Porphyrin Pentachloride, Fe Phthalocyanine, Hemin, Fe-Hematoporphyrin D (HPD), Fe-Acetoxyethyl vinyl Deuteroporphyrin, Fe-Protoporphyrin IX, Fe-Deuteroporphyrin 2, 4 bis acetal, Mn-TPPS.sub.4, Co-N.sup.+ MTPyP, Mn-N.sup.+ MTPyP, Co-Mesoporphyrin X, Protohemin, Deuterohemin, Meso-tetra (4-N methyl pyridyl) hemin tetraiodide, Meso-tetra (4-carboxy phenyl) hemin, Ni-TPPS, Ni-HPD, Mn-mesoporphyrin IX, Co-Protoporphyrin IX, Mn-Protoporphyrin IX, Sn-Protoporphyrin IX, Co-HPD, Mn-HPD, Gd-TPPS, Gd-HPD, Hematoporphyrin Mono-acetate-Fe, Ferretin-Fe, Ferredoxin-Fe(4), Transferrin-Fe, Hematoporphyrin Diacetate-Gd, GdFe -TPPS.sub.4, GdFe.sub.2 -HPD, FeTPPS.sub.4 (OH.sub.2).sub.2 ClO.sub.4 -, FeTPP (OH.sub.2).sub.2 ClO.sub.4 -, Fe-nitrolacetate, Fetetrasulfinated phalocyanine, Bisimidozole (FeTPPS)ClO.sub.4 -, Rubrium-ferricytochrome/C, and combinations thereof. 11. The process according to claim 10 wherein said metal-organic compound complexes are chemically complexed with dextran. 12. The process according to claim 11 wherein said composition is chemically complexed with an antibody. 13. A process for affecting molecules in the cell and subcellular structures in the tissue of a host organism comprising selecting particles of less than about 1 micron to affect the relative dipole moment and produce direct effects on subcellular structure and molecules in the cells of said tissue comprising introducing said particles into the living cells of said tissue wherein said particles are selected from the group consisting of: (a) cobalt, zinc, iron, chromium, nickel, platinum, rare earth metals and compounds selected from the group consisting of dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium; dysprosium sulfate, erbium sulfate, europium oxide, europium sulfate, gadolinium oxide, gadolinium sulfate, holmium oxide, samarium sulfate, terbrium sulfate, thulium oxide, ytterbium sulfide, Yttrium oxide, yttrium sulfate, yttrium ferrioxide (Y3Fe.sub.5 O.sub.12), yttrium oxide (Y.sub.3 Al.sub.5 O.sub.12), dysprosium-nickel, dysprosium-cobalt, gadolium-iron, ytterbium-iron, cobalt-smarium, gadoliumium-ytterbium, dysprosium-gallium, and actinide series elements and compounds thereof: (b) dextran metal complexes wherein said metal is selected from the group consisting of cobalt, zinc, chromium, gallium, manganese, nickel, platinum, dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium: (c) iron transporting and chelating compounds selected from the group consisting of ferric ammonium citrate, enterochelin, transferrin, metallothionein, hydroxamates, phenolate, ferrichromes, desferriferrichromes, ferritin, ferric mycobactins, ferredoxin and rubredoxin: (d) porphyrins selected from the group consisting of etioporphyrins, meso-porphyrins, coproporphyrins, etio porphyrin, protoporphyrins, dicarboxylic acid containing porphyrins, tetraphenylporphyrin sulfonate, chlorophylls, and cytochromes: (e) and cominbations of the materials of said sub-paragraphs (a), (b), (c) and (d). 14. The process of claim 13 wherein the dipole moment is enhanced by applying a static magnetic or electric field to said tissue. 15. The process of claim 1 comprising applying a localized static magnetic or electric field to said tissue to aid in the intracellular uptake and energy absorption of the electric or magnetic dipoles either introduced or already present in said tissue. 16. The process of claim 1 wherein a localized static magnetic or electric field is applied to said tissue after providing said particles to said host organisms but prior to or during the application of said alternating, oscillating or pulsed electromagnetic field to enhance the intracellular uptake of energy and the energy-absorption responsivenes of said particles. 17. The process of claim 15 wherein a localized static magnetic or electric field is applied to said tissue prior to or during the application of said alternating, oscillating or pulsed electromagnetic field to enhance the intracellular energy uptake and energy absorption of the electric or magnetic dipoles either introduced or already present in said tissue. 18. The process of claim 14 or 15 or 16 or 17, inclusive, wherein the static magnetic or electric field is between 100 gauss and 80 kilogauss. 19. The process of claim 1 wherein the treatment is continued to attain an increase of intracellular temperature of between 8.degree. Centigrade and 100.degree. Centigrade to kill cancer cells. 20. The process of claim 1 wherein said particles are selected so that when introduced into the extracellular environment of said tissue, said particles alter membrane events and potentiate energy delivery to said diseased cells or reduce energy delivery to said normal cells. 21. The process of claim 1 wherein particles are introduced intravenously, intra-arterially, intravenously, intra-arterially, intra-lymphatically, or locally. 22. The process of claim 1 where said diseased cells comprise antherosclerotic lesions. 23. The process of claim 1 wherein the composition of particles includes atherosclerotic agent and atherosclerotic specific antibody and said diseased cells comprise atherosclerotic lesions. 24. A process comprising selecting particles of less than about 1 micron to affect intracellular and extracellular events including membrane alterations to produce or alter nerve impulse formation or conduction by the selection of said particles and introducing said particles into a host organism that can form nerve impulses: subjecting said host organism to a relatively low frequency alternating, oscilating or pulsed electromagnetic field to provide energy to produce or alter said nerve impulses, wherein said particles are selected from the group consisting of: (a) cobalt, zinc, iron, chromium, nickel, platinum, rare earth metals and compounds selected from the group consisting of dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium; dysprosium sulfate, erbium sulfate, europium oxide, europium sulfate, gadolinium oxide, gadolinium sulfate, holmium oxide, samarium sulfate, terbium sulfate, thulium oxide, ytterbium sulfide, yttrium oxide, yttrium sulfate, yttrium ferrioxide (Y.sub.3 Fe.sub.5 O.sub.12), yttrium oxide (Y.sub.3 Al.sub.5 O.sub.12), dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-ytterbium, dysprosium-gallium, and actinide series elements and compounds thereof: (b) dextran metal complexes wherein said metal is selected from the group consisting of cobalt, zinc, chromium, iron, gallium, manganese, nickel, platinum, dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium Fe.sub.2 O.sub.3, Fe.sub.3 O.sub.4, FeOOH: (c) iron transporting and chelating compounds selected from the group consisting of ferric ammonium citrate, enterochelin, transferrin, metallothionein, hydroxamates, phenolates, ferrichromes, desferriferrichromes, ferritin, ferric mycobactins, ferredoxin and rubredoxin: (d) porphyrins selected from the group consisting of etioporphyrins, meso-porphyrins, uroporphyrins, coproporphyrins, protoporphyrins, dicarboxylic acid containing porphyrins, tetraphenylporphyrin sulfonate, hematoporphyrins, chlorophylls, and cytochromes: (e) and combinations of the materials of said sub-paragraghs (a), (b), (c) and (d). 25. The process of claim 1 wherein said particles are selected to include compositions specifically applicable to affecting intracellular and extracellular events including membrane alterations to produce or alter nerve impulse formation or conduction. 26. A process to measure the change in metabolism in living cells comprising introducing particles of less than about 1 micron into said cells and measuring the alteration in dielectric properties of said cells and correlating said measurements with metabolism in said cells wherein said particles are selected from the group consisting of: (a) cobalt, zinc, iron, chromium, nickel, platinum, rare earth metals and compounds selected from the group consisting of dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium; dysprosium sulfate, erbium sulfate, europium oxide, europium sulfate, gadolinium oxide, gadolinium sulfate, holmium oxide, samarium sulfate, terbium sulfate, thulium oxide, ytterbium sulfide, yttrium oxide, yttrium sulfate, yttrium ferrioxide (Y.sub.3 Fe.sub.5 O.sub.12), yttrium oxide (Y.sub.3 Al.sub.5 O.sub.12), dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-ytterbium, dysprosium-gallium, and actinide series elements and compounds thereof: (b) dextran metal complexes wherein said metal is selected from the group consisting of cobalt, zinc, chromium, iron, gallium, manganese, nickel, platinum, dysprosium, erbium, europium gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium Fe.sub.3 O.sub.4, Fe.sub.2 O.sub.3, FeOOH: (c) iron transporting and chelating compounds selected from the group consisting of ferric ammonium citrate, enterochelin, transferrin, metallothionein, hydroxamates, phenolates, ferrichromes, desferriferrichromes, ferritin, ferrin mycobactins, ferredoxin and rubredoxin: (d) porphyrins selected from the group consisting of etioporphyrins, meso-porphyrins, proporphyrins, coproporphyrins, protopophyrins, dicarboxylic acid containing porphyrins, tetraphenylporphyrin sulfonate, hematoporphyrins, chlorophylls, and cytochromes: (e) and combinations of the materials of said sub-paragraphs (a), (b), (c) and (d). 27. A process to follow the exact distribution of particles in living tissue comprising introducing particles of less than about 1 microns into said tissue and measuring the alteration in dielectric properties, conductivity and frequency dependent dispersion curves of said tissue with the introduction of particles into said tissue wherein said particles are selected from the group consisting of: (a) cobalt, zinc, iron, chromium, nickel, platinum, rare earth metals and compounds selected from the group consisting of dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium; dysprosium sulfate, erbium sulfate, europium oxide, europium sulfate, gadolinium oxide, gadolinium sulfate, holmium oxide, samarium sulfate, terbium sulfate, thulium oxide, ytterbium sulfide, yttrium oxide, yttrium sulfate, yttrium ferrioxide (Y.sub.3 Fe.sub.5 O.sub.12), yttrium oxide (Y.sub.3 Al.sub.5 O.sub.12), dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-ytterbium, dysprosium-gallium, and actinide series elements and compounds thereof: (b) dextran metal complexes wherein said metal is selected from the group consisting of cobalt, zinc, chromium, iron, gallium, manganese, nickel, platinum, dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, dysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium Fe.sub.2 O.sub.3, Fe.sub.3 O.sub.4, FeOOH: (c) iron transporting and chelating compounds selected from the group consisting of ferric ammonium citrate, enterochelin, transferrin, metallothionein, hydroxamates, phenolates, ferrichromes, desferriferrichromes, ferritin, ferric mycobactins, ferredoxin and rubredoxin: (d) porphyrins selected from the group consisting of etioporphyrins, meso-porphyrins, uroporphyrins, coproporphyrins, protogporphyrins, dicarboxylic acid containing porphyrins, tetraphenylporphyrin sulfonate, hematoporphyrins, chlorophylls, and cytochromes; (e) and combinations of the materials of said sub-paragraphs (a), (b) (c) and (d). 28. A process of claim 1 for affecting intracellular and extracellular events comprising subjecting said particles to ultrasound, said particles being selected to enhance the effect of ultrasound on said tissue. 29. The process of claim 1 wherein an alternating electromagnetic field between 1 Hz and 500 MHz is used to affect said particles and make them responsive to an exciting alternating electromagnetic field produced by magnetostrictive induced vibrations applied to said tissue. 30. The process of claim 1 wherein said particles are selected to include compositions that specifically affect intracellular and extracellular events in said tissue or said particles are affected to make them responsive to an exciting alternating electromagnetic field produced by magnetostrictive induced vibrations. 31. The process of claim 1 wherein an alternating electromagnetic field is applied to said particles to produce acoustic changes in said particles and affect the cellular and subcellular structures of said tissue. 32. The process of claim 1 wherein said particles are selected to acoustically affect intracellular and extracellular events in said tissue or said particle and affecting the cellular and subcellular structures of said tissue. 33. A process of claim 1 for the treatment of cancer where said diseased cells comprise cancer cells.

Details for Patent 4,767,611

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	PANHEMATIN	hemin for injection	For Injection	101246	07/20/1983		2040-01-28