Claims for Patent: 4,813,399

Summary for Patent: 4,813,399

Title:	Process for the treatment of neurological or neuromuscular diseases and development
Abstract:	The present invention describes a method for the treatment of neurological diseases and development and neuromuscular diseases and development with diagnostic applications to optimize the treatment modalities. The process involves the use of magnetic or electric dipoles which are present, capable of being induced or introduced into neurological or neuromuscular tissue and are capable of being activated by an external alternating electromagnetic field. The cells in the neurological or neuromuscular tissue may consist of neurons (central or peripheral) and supporting cells i.e. glial cells, oligodendrocytes, etc. The activation of these magnetic or electric dipole particles allows modulation and control of neuronal and supporting cell activity.
Inventor(s):	Gordon; Robert T. (Skokie, IL)
Assignee:
Application Number:	06/886,616
Patent Claims:	1. A process for the treatment of neurological or neuromuscular diseases and development without substantially damaging normal neuronal and supporting glial cells comprising: introducing to the neurological or neuromuscular tissue minute particles capable of being taken up by neuronal or glial cells, and allowing said introduced minutes particles to effect at least one event comprising intracellular events or membrane events in said neuronal or glial cells, and subjecting said neurological or neuromuscular tissue to a relatively low frequency electromagnetic field to selectively provide energy to said neuronal or glial cells to alter their function. 2. The process of claim 1 including, inducing magnetic or electric dipoles in said tissue or said cells. 3. The process of claim 1 including, introducing magnetic or electric dipoles into said tissue or said cells. 4. The process of claim 1 including, applying to said tissue a static magnetic or electric field. 5. The process of claim 1 including, said applying including said static magnetic or electric field being between 100 gauss and 80 kilogauss. 6. The process of claim 1 including, said subjecting step commencing generally after the completion of said introducing step. 7. The process of claim 1 including, said subjecting including said electromagnetic field being a relatively low frequency alternating electromagnetic field. 8. The process of claim 1 including, said subjecting including said electromagnetic field being a relatively low frequency oscillating electromagnetic field. 9. The process of claim 1 including, said subjecting including said electromagnetic field being a relatively low frequency pulsed electromagnetic field. 10. The process of claim 1 including, said subjecting including said electromagnetic field being between 1 Hz and about 100 MHz. 11. The process of claim 1 including, said subjecting including exciting said particles and raising the energy level of said tissue to destroy said cells or modify their behavior to decrease the degenerative process. 12. The process of claim 1 including, continuing said subjecting until an increase of intracellular temperature of between 8 and 100 degrees Centigrade is attained to modify, alter or kill disceased cells of said tissue. 13. The process of claim 1 including, introducing particles into the extracellular environment of said tissue to alter membrane events and potentiate energy delivery to diseased inflammatory or reactive cells or reduce energy delivery to normal cells. 14. The process of claim 1 including, said introducing including introducing said particles intravenously, intra-arterially, intra-lymphatically or locally into cerebrospinal fluid for ultimate delivery to reactive or inflammatory diseased cells. 15. The process of claim 1 including, selecting said particles to enhance the effect of ultrasound on said tissues and said cells, and thereafter, subjecting said particles to ultrasound. 16. The process of claim 1 including, producing an exciting alternating electromagnetic field by magnetostrictive induced vibrations, and applying to said tissue and said cells said exciting alternating electromagnetic field. 17. The process of claim 16 including, said subjecting including said field being an alternating electromagnetic field between 1 Hz and 500 MHz to affect said particles and make them more or less responsive to said exciting alternating electromagnetic field. 18. The process of claim 16 including, affecting said particles to make them more or less responsive to said exciting alternating electromagnetic field. 19. The process of claim 16 including, selecting said particles to include compositions that specifically affect intracellular and extracellular events in said tissue and cells. 20. The process of claim 1 including, selecting said particles to include compositions that specifically affect intracellular and extracellular events in said tissue and cells. 21. The process of claim 1 including, affecting said particles to make them more or less responsive to an exciting alternating electromagnetic field produced by magnetostrictive induced vibrations. 22. The process of claim 1 including, applying an alternating electromagnetic field of said particles to produce acoustic changes in said particles and affect the cellular and subcellular structures of said tissues or cells. 23. The process of claim 1 including, selecting said particles to acoustically affect intracellular and extracellular events in said tissue and cells or said particles and to affect the cellular and subcellular structures of said tissue and cells. 24. The process of claim 1 including, modifying the function of neural cells, glial cells, nerves to neuromuscular structures. 25. The process of claim 1 including, modulating the function of neural cells, glial cells, nerves or neuromuscular structures. 26. The process of claim 1 including, modifying conduction in central and peripheral nerves and tracts in the central nervous system. 27. The process of claim 1 including, choosing said particles in their size, shape, composition and conformation to be transported along a specific path or tract to a specific destination to modulate activity at the destination. 28. The process of claim 1 including, choosing said particles in their size, shape, composition and conformation to be transported along a specific path or tract and modulate or affect activity in that path or tract including conductiion mechanisms. 29. The process of claim 1 including, obtaining control of neurological, neuromuscular and other tissue during developmental phases and formation to help control development and function of the tissue. 30. The process of claim 1 including, obtaining control to modulate and affect the conduction of nerve impulses. 31. The process of claim 1 including, achieving modulation or control of the release of neurotransmitters at synapses or neuromuscular junctions. 32. The process of claim 1 including, choosing said particles in their size, shape, conformation and composition to be taken up by subcellular components such as the mitochondria. 33. The process of claim 31 including, controlling the metabolism in said cells. 34. The process of claim 1 including, designing said particles to interact with the cell membrane or receptors to modulate and control conduction in the nerve and other cellular events. 35. The process of claim 1 including, using chloroquin ammonium chloride, methylamine or similar agents to decrease uptake of said particles in certain cells to potentiate the effect in the remaining cells. 36. The process of claim 1 including, choosing said particles in their composition, conformation, size and shape to produce an affect in a specific pathway as in myelinated versus unmyelinated. 37. The process of claim 1 including, choosing said particles in their composition, conformation, size and shape to interact with the myelin layer in nerves and therefore modify nerve conduction. 38. The process of claim 1 including, choosing said particles in their composition, conformation, size and shape to interact with the myelin layer in nerves and affect myelin related diseases, i.e., the demyelinating diseases. 39. The process of claim 1 including, choosing said particles so that they are adapted to be, after said introducing step, taken up by glial cells, i.e. oligodendrocytes, and used to affect the function of the supporting cells and their interaction with neuronal cells. 40. The process of claim 1 including, choosing said particles to interact with the neuromuscular junction and thereby control and modulate neuromuscular activity. 41. The process of claim 1 including, choosing said particles in their size, shape, conformation and composition to be taken up by the unmyelinated pathways and to affect those pathways and their ultimate destination. 42. The process of claim 1 including, achieving control and modulation of the visual pathway or retinal ganglion cells. 43. The process of claim 1 including, using the differential in the rate of transport in different pathways of said particles to selectively affect one pathway or destination prior to, simultaneously with, or after another pathway or destination. 44. The process of claim 1 including, said introducing including introducing said particles intravenously, intra-arterially or intra-lymphatically. 45. The process of claim 1 including, said introducing including introducing said particles into the cerebrosphinal fluid. 46. The process of claim 1 including, said introducing including introducing said particles directly into said tissue. 47. The process of claim 1 including, said particles being ferromagnetic, paramagnetic or diamagnetic. 48. The process of claim 1 including, said particles being colloidally suspended and under one micron in size. 49. The process of claim 1 including, selecting said particles from the group comprising ferromagnetic, paramagnetic, and diamagnetic elements, inorganic compounds, organic compounds and combinations thereof, metalloporphyrins, Fe.sub.2 O.sub.3, FeOOH, and metalloporphyrins. 50. The process of claim 1 including, selecting said particles from the group comprising ferromagnetic, paramagnetic, and diamagnetic elements, inorganic compounds, organic compounds and combinations or complexes thereof, metalloporphyrins, Fe.sub.2 O.sub.3, FeOOH, and metalloporphyrins. 51. The process of claim 50 including, selecting said particles from the group comprising: (a) cobalt, zinc, iron, chromium, nickel, platinum, rare earth metals such as dysprosium, erbium, europium, gadolinium, holmium, samarium, terbium, thulium, ytterbium, yttrium, and compounds thereof comprising 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; and combinations thereof. 52. The process of claim 50 including, selecting said organic compounds from the group comprising: (a) dextran metal complexes wherein said metal is selected from the group comprising 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 such as 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 comprising ferric ammonium citrate, enterochelin, transferrin, metallothionein, hydroxamates, phenolates, ferrichromes, desferriferrichromes, ferritin, ferric mycobactins and iron sulfur proteins comprising ferredoxin and rubredoxin, (c) porphyrins comprisng etioporphyrins, meso-porphyrins, uroporphyrins, coproporphyrins, protoporphyrins, dicarboxylic acid containing porphyrins, substituted prophyrins comprising tetraphenylporphyrin sulfonate and protoporphyrin containing molecules comprising hematoporphyrins, chlorophylls, and cytochromes, and combinations thereof. 53. The process of claim 52 including, substituting the natural occurring metal moiety of said porphyrin with a metal selected from 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, ytterbium-iron, cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium, and combinations thereof. 54. The process of claims 52 or 53 including, said iron transporting, iron chelating and porphyrin compounds being chemically complexed with dextran. 55. The process of claim 54 including, said composition being chemically complexed with an antibody. 56. The process of claim 52 including, selecting said metal-organic compound complexes 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-TPPS4, CO-N.sup.+ MTPyP, Mn-N.sup.+ MTPyP, Co-Mesoporphyrin X, Protochemin, Deuterchemin, 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, Fetetransulfinated phalocyanine, Bisimidozole (FeTPPS) ClO.sub.4 -, Rubrium-ferricytochrome/C, and combinations thereof. 57. The process of claim 56 including, said metal-organic compound complexes being chemically complexed with dextran. 58. The process of claim 57 including, said composition being chemically complexed with an antibody. 59. The process of claim 1 including, using magnetic or electric dipoles already present in said tissues or said cells. 60. The process of claim 1 including, said subjecting including said electromagnetic field activating magnetic or electric dipoles present in said tissues or said cells. 61. A process for the treatment of neurological or neuromuscular diseases and development without substantially damaging normal neuronal and supporting glial cells comprising: introducing to the neurological or neuromuscular tissue minute particles capable of being taken up by neuronal or glial cells, and allowing said introduced minute particles to effect at least one event comprising intracellular events or membrane events in said neuronal or glial cells, and subjecting said neurological or neuromuscular tissue to a relatively low frequency electromagnetic field to activate magnetic or electric dipoles present in said tissue or said cells.

Details for Patent 4,813,399

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