Claims for Patent: 4,758,429

Summary for Patent: 4,758,429

Title:	Method for the treatment of arthritis and inflammatory joint diseases
Abstract:	The present invention describes a method for the treatment of arthritis and joint diseases with diagnostic applications to enhance the treatment process. The process involves the utilization of magnetic or electric dipoles which are present, capable of being induced, or introduced into the cell of the joint and are capable of being activated by an external alternating electromagnetic field. The activation of these magnetic or electric dipoles (particles) allows destruction of the reactive cells and alteration of the intracellular processes with a dimunition of the destructive process.
Inventor(s):	Gordon; Robert T. (Skokie, IL)
Assignee:
Application Number:	06/794,545
Patent Claims:	1. A process for the treatment of arthritis and other non-infections joint diseases by affecting particles present and/or introduced intracellularly into reactive and/or inflammatory diseased cells in the joint and joint space without substantially damaging normal cells, providing to said host joint minute particles capable of being taken up by said reactive and/or inflammatory diseased joint cells, allowing said particles to effect at least one event comprising intracellular events and membrane events in said reactive and/or inflammatory diseased cells in the joint space and area, subjecting said joint space and area to a relatively low frequency alternating, oscillating and/or pulsed electromagnetic field to provide energy to reactive and/or inflammatory diseased cells and selectively heat said reactive and/or inflammatory diseased joint cells. 2. The process of claim 1 including the utilization of magnetic or electric dipoles present or capable of being induced in the joint or in the reactive and/or inflammatory diseased cells of the joint or in the joint space. 3. The process of claims 1 or 2 wherein particles are introduced intravenously, intra-arterially, or intra-lymphatically. 4. The process of claims 1 or 2 wherein particles are introduced directly into the joint and/or joint space. 5. The process of claims 1 or 2 wherein particles are ferromagnetic, paramagnetic or diamagnetic. 6. The process of claims 1 or 2 wherein particles are colloidally suspended and under one micron in size. 7. The process of claims 1 or 2 wherein said particles are selected from the group consisting of ferromagnetic, paramagnetic and diamagnetic elements, inorganic compounds, organic compounds and combinations thereof metalloporphyrins, Fe.sub.2 O.sub.3, FeOOH, and metal metalloporphyrins. 8. The process of claim 7 wherein said particles are selected from the group consisting of (a) cobalt, zinc, iron, chromium, nickel, platinum, rare earth metals consisting of dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium and compounds thereof consisting of 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, ysprosium cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium, gadolinium-ytterbium, dysprosium-gallium, and actinide series elements and compounds thereof; and combinations thereof. 9. The process of claim 7 wherein said organic compounds are selected from the group consisting of; (a) 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, and iron consisting of Fe.sub.2 O.sub.3 particles, Fe.sub.3 O.sub.4 particles and FeOOH particles and Fe.sub.2 O.sub.3 -dextran complexes, Fe.sub.3 O.sub.4 -dextran complexes, and FeOOH-dextran complexes; (b) iron transporting and chelating compounds consisting of ferric ammonium citrate, enterochelin, transferrin, metallothionein, hydroxamates, phenolates, ferrichromes, desferriferrichromes, ferritin, ferric mycobactins and iron sulfur proteins consisting of ferredoxin and rubredoxin; (c) porphyrins comprising etioporphyrins, meso-porphyrins, uroporphyrins, coproporphyrins, protoporphyrins, dicarboxylic acid containing porphyrins, substituted porphyrins consisting of tetraphenylporphyrin sulfonate and protoporphyrin containing molecules consisting of hematoporphyrins, chlorophylls, and cytochromes; and combinations thereof. 10. The process of claim 9 wherein said prophyrin is one in which the natural occurring metal moiety is substituted with a metal selected from the group consisting of 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. 11. The process according to claims 9 or 10 wherein said iron transporting, iron chelating and porphyrin compounds are chemically complexed with dextran. 12. The process according to claim 11 wherein said composition is chemically complexed with an antibody. 13. The process according to claim 9 wherein the metal-organic compound complexes are selected from the group consisting of 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. 14. The process according to claim 13 wherein said metal-organic compound complexes are chemically complexed with dextran. 15. The process according to claim 14 wherein said composition is chemically complexed with an antibody. 16. A process for affecting molecules in the joint cell and subcellular structures in the tissue of a host organism comprising applying a constant magnetic field to said tissue to affect the relative dipole moment and producing direct effects on subcellular structures and molecules in the cells of said tissue by introducing particles into the living cells of said tissue. 17. The process of claim 16 wherein the constant magnetic field is initially utilized and thereafter applying an alternating electromagnetic field to achieve an enhanced effect. 18. A process for the diagnosis of non-infectious joint disease through the use of intra-articular particles which may be intracellular in the cells contained in the joint. 19. The process of claim 1 wherein magnetic susceptibility measurements are performed to diagnose the involved joints by the uptake of the particles. 20. The process of claim 1 wherein magnetic mapping measurements are performed to diagnose the involved joints. 21. The process of claim 20 wherein magnetic susceptibility measurements are performed to determine the optimum time of treatment. 22. The process of claim 19 wherein magnetic susceptibility and magnetic mapping measurements are performed to help diagnose the type of disease process present in the joint. 23. The process of claim 1 or 2 comprising applying a localized static magnetic or electric field to joint tissue to aid in the intracellular uptake and energy absorption of the electric or magnetic dipoles either introduced or already present in said joint. 24. The process of claims 1 and 2 wherein a localized static magnetic or electric field is applied to said joint after providing said particles but prior to or during the application of said alternating, oscillating and/or pulsed electromagnetic field to enhance the intracellular uptake of energy and the energy-absorption responsiveness of said particles in joint. 25. The process of claim 17 wherein a localized static magnetic or electric field is applied to the joint prior to and/or during the application of said alternating, oscillating and/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 the joint. 26. The process of claims 1 or 2 wherein a constant magnetic field through interaction with intracellular dipoles in the joint is utilized to modify the behavior of the reactive and/or inflammatory diseased cells of the joint to slow the degenerative process. 27. The process of claim 16 wherein the static magnetic or electric field is between 100 gauss and 80 kilogauss. 28. The process of claims 1 or 2 wherein said alternating, oscillating and/or pulsed electromagnetic field is between 1 Hz to about 100 MHz. 29. The process of claims 1 or 2 including an external alternating electromagnetic field applied to excite the particles and raise the energy level in the reactive and/or inflammatory diseased cells of the joint to destroy said joint cells or modify their behavior to decrease the joint degenerative process. 30. The process of claims 1 or 2 wherein the treatment is continued to attain an increase of intracellular temperature of between 8 Centigrade and 100 Centigrade to modify, alter, and/or kill the reactive and/or inflammatory diseased cells of the joint. 31. The process of claims 1 or 2 wherein particles are introduced into the extracellular environment of said joint tissue to alter membrane events and potentiate energy delivery to said diseased inflammatory and/or reactive joint cells and/or reduce energy delivery to said normal joint cells. 32. The process of claims 1 or 2 wherein particles are introduced intravenously, intra-arterially, intra-lymphatically, and/or locally, for ultimate delivery to the reactive and/or inflammatory diseased cells of the joint. 33. The process for measurement of temperature in living tissue and cells in the joint comprising measuring the alteration in dielectric properties, conductivity and frequency dependent dispersion curves in living joint tissue and cells with temperature. 34. The process of claim 33 comprising measuring said temperature along three axes at right angles in a host joint organism and producing a three-dimensional temperature map of the body from said measurements. 35. A process to measure the change in metabolism in living joint cells comprising measuring the alteration in dielectric properties of said joint cells and correlating said measurements with metabolism in said joint cells. 36. A process to follow the exact distribution of particles in living joint tissue and cells comprising measuring the alteration in dielectric properties, conductivity and frequency dependent dispersion curves of said tissue and joint cells with the introduction of particles into said tissue and joint cells. 37. A process of claims 1 or 2 for affecting intracellular and extracellular events comprising subjecting said particles to ultrasound, said particles being selected to enhance the effect of ultrasound on said joint tissue and cells. 38. A process of claim 7 for affecting intracellular and extracellular events comprising subjecting said particles to ultrasound, said particles being selected to enhance the effect of ultrasound on said joint tissue and joint cells. 39. The process of claims 1 or 2 wherein an alternating electromagnetic field between 1 Hz and 500 MHz is used to affect said particles and make them more or less responsive to an exciting alternating electromagnetic field produced by magnetostrictive induced vibrations applied to said joint tissues and joint cells. 40. The process of claim 7 wherein said particles are selected to include compositions that specifically affect intracellular and extracellular events in said joint tissues and tissue cells or said particles are affected to make them more or less responsive to an exciting alternating electromagnetic field produced by magnetostrictive induced vibrations. 41. The process of claims 1 or 2 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 joint tissues and/or joint cells. 42. The process of claim 7 wherein said particles are selected to acoustically affect intracellular and extracellular events in said joint tissues and joint cells or said particle and affecting the cellular and subcellular structures of said joint tissues and joint cells. 43. The process of claims 1 or 2 wherein magnetic susceptibility measurements are performed to diagnose the involved joints by the uptake of the particles. 44. The process of claims 1 or 2 wherein magnetic mapping measurements are performed to diagnose the involved joints. 45. The process of claim 44 wherein magnetic susceptibility measurements are performed to determine the optimum time of treatment. 46. The process of claim 43 wherein magnetic susceptibility and magnetic mapping measurements are performed to help diagnose the type of disease process present in the joint. 47. The process of claim 44 wherein magnetic susceptibility and magnetic mapping measurements are performed to help diagnose the type of disease process present in the joint. 48. The process of claim 17 wherein a localized static magnetic or electric field is applied to the joint prior to and/or during the application of said alternating, oscillating and/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 the joint. 49. The process of claim 23 wherein a localized static magnetic or electric field is applied to the joint prior to and/or during the application of said alternating, oscillating and/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 the joint. 50. The process of claim 16 wherein the static magnetic or electric field is between 100 gauss and 80 kilogauss. 51. The process of claim 17 wherein the static magnetic or electric field is between 100 gauss and 80 kilogauss. 52. The process of claim 23 wherein the static magnetic or electric field is between 100 gauss and 80 kilogauss. 53. The process of claim 24 wherein the static magnetic or electric field is between 100 gauss and 80 kilogauss. 54. The process of claim 25 wherein the static magnetic or electric field is between 100 gauss and 80 kilogauss. 55. A process for the treatment of arthritis and non-infections joint diseases comprising: introducing into the joint or joint space minute particles capable of being taken up by the reactive and/or inflammatory diseased joint cells and of responding to a relatively low frequency electromagnetic field, and after said introducing, subjecting the joint or joint space to a relatively low frequency electromagnetic field having a frequency of less than 500 megahertz to energize and selectively heat said reactive and/or inflammatory diseased cells without substantially damaging the normal cells. 56. The process of claim 50 including, said subjecting including said frequency being selected to enhance the dielectric properties, conductivity and electric dipoles of the joint cells. 57. The process of claim 50 including, said subjecting including said field having a frequency between 1 hertz and 100 megahertz. 58. The process of claim 50 including, said subjecting including using capacitor plates to generate said field. 59. The process of claim 50 including, said subjecting including using a coil arrangement to generate said field. 60. The process of claim 50 including, said subjecting including using electrodes to generate said field. 61. The process of claim 50 including, said subjecting including said field being an alternating electromagnetic field. 62. The process of claim 50 including, said subjecting including said field being an oscillating electromagnetic field. 63. The process of claim 50 including, said subjecting including said field being a pulsing electromagnetic field. 64. The process of claim 50 including, before said subjecting, allowing said particles to effect at least one event comprising intracellular events and membrane events in said reactive or inflammatory diseased cells. 65. The process of claim 50 including, said introducing including said particles being introduced intravenously. 66. The process of claim 50 including, said introducing including said particles being introduced intra-arterially. 67. The process of claim 50 including, said introducing including said particles being less than one micron in size and colloidally suspended. 68. The process of claim 50 including, said introducing including said particles being absorbed into the joint cell and altering the intracellular environment and the charge accumulation on the membrane. 69. The process of claim 50 including, said introducing including said particles being ferromagnetic, paramagnetic, or diamagnetic. 70. The process of claim 50 including, said introducing including said particles being introduced directly into the joint and/or joint space. 71. The process of claim 50 including, said introducing including introducing said particles into the extracellular environment of the joint tissue. 72. The process of claim 50 including, after said introducing and before said subjecting, evaluating which joints are affected by the disease process by analyzing which joint takes up said particles. 73. The process of claim 73 including, said analyzing including using magnetic susceptibility measurements. 74. The process of claim 50 including, imparting a dipole to said particles before said subjecting step. 75. The process of claim 50 including, applying a constant magnetic field to the joint before said subjecting step. 76. The process of claim 75 including, said subjecting including said field being an alternating electromagnetic field. 77. The process of claim 50 including, performing magnetic susceptibility measurements to determine the optimum time of said subjecting step. 78. The process of claim 50 including, performing magnetic susceptibility and magnetic mapping measurements to help diagnose the type of disease process present in the joint. 79. The process of claims 1, 16, 19, 36 or 55 wherein the particles are metal containing organic molecules. 80. The process of claims 1, 16, 19, 36 or 55 wherein the particles are iron containing organic molecules.

Details for Patent 4,758,429

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