CHEMICALLY INDUCED INTRACELLULAR HYPERTHERMIA

• US 20100056643A1
• Filed: 11/05/2009
• Published: 03/04/2010
• Est. Priority Date: 07/27/1998
• Status: Abandoned Application

• Current Assignee: St Jude Pharmaceuticals Incorporated
• Original Assignee: St Jude Pharmaceuticals Incorporated
• Inventors: Bachynsky, Nicholas, Roy, Woodie
• Application Number:
  US12/613,189
• Publication Number:
  US 20100056643A1
• Time in Patent Office: Days
• US Class Current: 514/728
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/06 the aromatic ring being substituted by nitro groups
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An invention relating to therapeutic pharmacological agents and methods to chemically induce intracellular hyperthermia and/or free radicals for the diagnosis and treatment of infections, malignancy and other medical conditions. The invention relates to a process and composition for the diagnosis or killing of cancer cells and inactivation of susceptible bacterial, parasitic, fungal, and viral pathogens by chemically generating heat, and/or free radicals and/or hyperthermia-inducible immunogenic determinants by using mitochondrial uncoupling agents, especially 2,4 dinitrophenol and, their conjugates, either alone or in combination with other drugs, hormones, cytokines and radiation.

Claims

1-54. -54. (canceled)

55. A method for inducing intracellular hyperthermia in a subject comprising the step of administering an amount of a mitochondrial uncoupling agent sufficient to the subject to thereby induce whole body intracellular hyperthermia in the subject, wherein the induced intracellular hyperthermia in the subject is sufficient to treat a cancer in the subject

56. The method of claim 55 wherein the cancer is selected from the group consisting of prostate carcinoma, glioblastoma multiform, Kaposi'"'"'s sarcoma, peritoneal carcinomatosis, and glioma and combinations thereof.

57. The method of claim 55, wherein the mitochondrial uncoupling agent is 2,4-dinitrophenol and/or a conjugate thereof.

58. The method of claim 56, wherein the mitochondrial uncoupling agent is 2,4-dinitrophenol and/or a conjugate thereof.

59. The method of claim 55, further comprising the step of administering a second medication, wherein the second medication increases

a) the overall metabolic rate of the subject,

b) the metabolic rate of a specific target tissue in the subject, and/or

c) free radical flux in the subject.

60. The method of claim 59, wherein the second medication is selected from the group consisting of glucagon, arbutamine, dobutamine, vasopressin, glutamine, proline, octanoate, methylene blue (tetramethylthionine), ubiquinone, menadione, hematoprophyrin, polyunsaturated fatty acids, monounsaturated fatty acids and combinations thereof.

61. The method of claim 55, wherein the induced intracellular hyperthermia is sufficient to cause the induction of heat shock proteins in a cell of the subject.

62. The method of claim 55, further comprising the step of administering to the subject an anti-cancer agent selected from the group consisting of metholtrexate, mercaptopuorine, fluorouracil, cytarabine, thioguanine, azacitidine, etoposide (VP-16) and teniposide (VM-26), vincristine, vinblastine, paclitaxel, busulfan, cyclophosphamide, mechlorethamine, melphalan, altaretarnine, ifosfamide, cisplatin, dacarbazine, procarbazine, lomustine, carmustine, lomustine, semustine, chlorambucil, thiotepa, carboplatin;

flutamide, prednisone, ethinyl estradiol, diethylstilbestrol, hydroxyprogesterone caproate, medroxyprogesterone, megestrolacetate, testosterone, fluoxymesterone, diiodothyroidine, triiodothyroidine, tetraiodothyroidine, aromatase inhibitor, amino glutethimide, octreotide, goserilin acetate, leuprolide, interferon alpha-2a, interferon alpha-2b, interferon-gamma, interferon-beta, interleukin-1, interleukin-2, interleukin-4, interleukin-10, anti-HER-2/neu humanized antibody, tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, macrophage-colony-stimulating factor, phenylacetates, retinoic acids, leukotrienes, thromboxanes, and combinations thereof.

63. The method of claim 55, further comprising administering radiation to the subject.