Water-soluble compound

• US 20070149496A1
• Filed: 08/20/2004
• Published: 06/28/2007
• Est. Priority Date: 10/31/2003
• Status: Abandoned Application

• Current Assignee: Technology Innovations, LLC
• Original Assignee: Technology Innovations, LLC
• Inventors: Goss, Kendrick, Curry, Stephen, Tuszynski, Jack, Greenwald, Howard
• Application Number:
  US10/923,615
• Publication Number:
  US 20070149496A1
• Time in Patent Office: Days
• US Class Current: 514/184
• CPC Class Codes: A61K 41/0004 Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092

Abstract

A water-soluble magnetic anti-mitotic compound with a water-solubility of at least 100 micrograms per milliliter, a molecular weight of at least 150 grams per mole, a mitotic index factor of at least 10 percent, a positive magnetic susceptibility of at least 1,000×10⁻⁶ cgs, and a magnetic moment of at least 0.5 bohr magnetrons, wherein said compound is comprised of at least 7 carbon atoms and at least one inorganic atom with a positive magnetic susceptibility of at least 200×10⁻⁶ cgs.

Claims

1. A water-soluble magnetic anti-mitotic compound with a water-solubility of at least 100 micrograms per milliliter, a molecular weight of at least 150 grams per mole, a mitotic index factor of at least 10 percent, a positive magnetic susceptibility of at least 1,000×

10<sup>−

6</sup> cgs, and a magnetic moment of at least 0.5 bohr magnetrons, wherein said compound is comprised of at least 7 carbon atoms and at least one inorganic atom with a positive magnetic susceptibility of at least 200×

10<sup>−

6</sup> cgs.

2. The compound as recited in claim 1, wherein said compound has a mitotic index factor of at least about 20 percent.

3. The compound as recited in claim 1, wherein said compound has a mitotic index factor of at least about 30 percent.

4. The compound as recited in claim 1, wherein said compound has a mitotic index factor of at least about 50 percent.

5. The compound as recited in claim 1, wherein said compound has a molecular weight of at least 300 grams per mole.

6. The compound as recited in claim 1, wherein said compound has a molecular weight of at least 400 grams per mole.

7. The compound as recited in claim 1, wherein said compound has a molecular weight of at least 1,000 grams per mole.

8. The compound as recited in claim 1, wherein said compound has a molecular weight of at least 1,200 grams per mole.

9. The compound as recited in claim 1, wherein said compound has a positive magnetic susceptibility of at least 5,000×

10<sup>−

6</sup> cgs.

10. The compound as recited in claim 1, wherein said compound has a positive magnetic susceptibility of at least 10,000×

10<sup>−

6</sup> cgs.

11. The compound as recited in claim 1, wherein said compound is comprised of at least about 10 carbon atoms.

12. The compound as recited in claim 1, wherein said compound is comprised of at least about 13 carbon atoms.

13. The compound as recited in claim 12, wherein said compound is comprised of at least one aromatic ring.

14. The compound as recited in claim 12, wherein said compound is comprised of at least two aromatic rings.

15. The compound as recited in claim 1, wherein said compound is comprised of at least 17 carbon atoms.

16. The compound as recited in claim 1, wherein said compound is comprised of least one oxetane group.

17. The compound as recited in claim 1, wherein said oxetane group is unsubstituted.

18. The compound as recited in claim 1, wherein said compound is comprised of an acetyl group.

19. The compound as recited in claim 18, wherein said acetyl group is linked to an unsaturated ring structure that is comprised of from about 6 to about 10 carbon atoms.

20. The compound as recited in claim 1, wherein said compound is comprised of two unsaturated ring structures.

21. The compound as recited in claim 20, wherein said two unsaturated ring structures are linked by an amide structure comprised of an acyl group.

22. The compound as recited in claim 21, wherein said acyl group is of the formula—

CONR₁ —

, wherein R₁ is selected from the group consisting of hydrogen and a lower alkyl of from 1 to about 6 carbon atoms.

23. The compound as recited in claim 1, wherein said compound is comprised of at least one saturated ring structure comprising from about 6 to about 10 carbon atoms.

24. The compound as recited in claim 23, wherein said saturated ring structure is selected from the group consisting of cyclohexane, cycloheptane, cyclooctane, cyclononane, and cylcodecane.

25. The compound as recited in claim 24, wherein said saturated ring structure is bonded to at least one quinone group.

26. The compound as recited in claim 1, wherein said compound is comprised of a partially unsaturated ring structure that contains no more than one double bond.

27. The compound as recited in claim 1, wherein said compound is comprised of a ring structure that contains no more than two double bonds.

28. The compound as recited in claim 26, wherein said partially unsaturated ring structure is comprised of partially unsaturated cyclohexane, partially unsaturated cyclopheptane, partially unsaturated cyclooctane, partially unsaturated cyclononane, partially unsaturated cyclodecane, and mixtures thereof.

29. The compound as recited in claim 27, wherein said partially unsaturated ring structure is comprised of partially unsaturated cyclohexane, partially unsaturated cycloheptane, partially unsaturated cyclooctane, partially unsaturated cyclononane, partially unsaturated cyclodecane, and mixtures thereof.

30. The compound as recited in claim 1, wherein said inorganic atom has a positive magnetic susceptibility of at least 200×

10<sup>−

6</sup> cgs.

31. The compound as recited in claim 1, wherein said inorganic atom has a positive magnetic susceptibility of at least 500×

10<sup>−

6</sup> cgs.

32. The compound as recited in claim 1, wherein said inorganic atom has a positive magnetic susceptibility of at least 1,000×

10<sup>−

6</sup> cgs.

33. The compound as recited in claim 1, wherein said inorganic atom is radioactive.

34. The compound as recited in claim 1, wherein said compound is comprised of a radioactive atom.

35. The compound as recited in claim 34, wherein said radioactive atom is radioactive carbon.

36. The compound as recited in claim 34, wherein said radioactive atom is radioactive hydrogen.

37. The compound as recited in claim 34, wherein said radioactive atom is radioactive phosphorus.

38. The compound as recited in claim 34, wherein said radioactive atom is radioactive sulfur.

39. The compound as recited in claim 34, wherein said radioactive atom is radioactive potassium.

40. The compound as recited in claim 1, wherein said compound is comprised of a radioactive nuclide.

41. The compound as recited in claim 1, wherein said compound has a magnetic moment of at least about 1.0 Bohr magnetrons per molecule.

42. The compound as recited in claim 1, wherein said compound has a magnetic moment of at least about 2 Bohr magnetrons per molecule.

43. The compound as recited in claim 1, wherein said compound has a water solubility of at least 500 micrograms per milliliter.

44. The compound as recited in claim 1, wherein said compound has a water solubility of at least 1,000 micrograms per milliliter.

45. The compound as recited in claim 1, wherein said compound has a water solubility of at least 2,500 micrograms per milliliter.

46. The compound as recited in claim 1, wherein said compound has a water solubility of at least 5,000 micrograms per milliliter.

47. The compound as recited in claim 1, wherein said compound has a water solubility of at least 10,000 micrograms per milliliter.

48. The compound as recited in claim 1, wherein said compound is comprised of a hydrophilic group.

49. The compound as recited in claim 48, wherein said hydrophilic group is a siderophore group.

50. The compound as recited in claim 49, wherein said siderophore group is bound to a magnetic moiety.

51. The compound as recited in claim 50, wherein said magnetic moiety is an iron atom.

52. The compound as recited in claim 48, wherein said hydrophilic group is a hydroxyl group.

53. The compound as recited in claim 48, wherein said hydrophilic group is a carboxyl group.

54. The compound as recited in claim 48, wherein said hydrophilic group is a carboxyl group.

55. The compound as recited in claim 48, wherein said hydrophilic group is an amino group.

56. The compound as recited in claim 48, wherein said hydrophilic group is an organometallic group.

57. The compound as recited in claim 48, wherein said hydrophilic group is a phosphate group.

58. The compound as recited in claim 48, wherein said hydrophilic group is biologically inert.

59. The compound as recited in claim 1, wherein said compound has an association rate with microtubules of at least 3,500,000/mole/second.

60. The compound as recited in claim 1, wherein said compound has a dissociation rate with microtubules of less than about 0.8/second, when measured at a temperature of 37 degrees Celsius and under atmospheric conditions.

61. The compound as recited in claim 1, wherein said compound has a dissociation rate with microtubules of less than about 0.7/second, when measured at a temperature of 37 degrees Celsius and under atmospheric conditions.

62. The compound as recited in claim 1, wherein said compound has a dissociation rate with microtubules of less than about 0.6/second, when measured at a temperature of 37 degrees Celsius and under atmospheric conditions.

63. A method of treating neoplasia in a subject in need of treatment, comprising administering to the subject an amount of paclitaxel effective to treat the neoplasia, in combination with an amount of the water-soluble anti-mitotic compound recited in claim 1 effective to treat the neoplasia, wherein a synergistic antineoplastic effect results.

64. The method as recited in claim 63, wherein the neoplasia is a carcinoma, a lymphocytic leukemia, a myeloid leukemia, a malignant lymphoma, a malignant melanoma, a myeloproliferative disease, a sarcoma, or a mixed type of neoplasia.

65. The method as recited in claim 64, wherein administration is concurrent.

66. The method as recited in claim 64, wherein administration is sequential.

67. A synergistic combination of antineoplastic agents, comprising an effective antineoplastic amount of paclitaxel and an effective antineoplastic amount of the anti-mitotic compound recited in claim 1.

68. The synergistic combination as recited in claim 67, wherein said anti-mitotic compound has a water-solubility of at least 100 micrograms per milliliter.

69. The synergistic combination as recited in claim 67, wherein a separate, individual formulation of paclitaxel is combined with a separate, individual formulation of said anti-mitotic compound.

70. The synergistic combination as recited in claim 67, wherein said anti-mitotic compound has a mitotic index factor of at least 20 percent.

71. The synergistic combination as recited in claim 67, wherein said anti-mitotic compound has a positive magnetic susceptibility of at least 5,000×

10<sup>−

6</sup> cgs.

72. The synergistic combination as recited in claim 67, wherein said anti-mitotic compound is comprised of at least 10 carbon atoms.

73. The synergistic combination as recited in claim 67, wherein said inorganic atom is radioactive.

74. The synergistic combination as recited in claim 67, wherein said inorganic atom has a magnetic moment of at least 1.0 bohr magnetron.

75. The synergistic combination as recited in claim 67, wherein said anti-mitotic compound has a mitotic index factor of at least about 50 percent.

76. The synergistic combination as recited in claim 75, wherein said anti-mitotic compound has a positive magnetic susceptibility of at least 10,000×

10<sup>−

6</sup> cgs.

77. The synergistic combination as recited in claim 67, wherein said inorganic atom has a magnetic moment of at least 2.0 bohr magnetrons.

78. A process for treating a biological organism comprised of a tubulin molecule, comprising the step of binding to said tubulin molecule the anti-mitotic compound recited in claim 1.

79. The process as recited in claim 78, wherein said tubulin molecule is a beta-tubulin molecule.

80. The process as recited in claim 78, wherein said anti-mitotic compound has a mitotic index factor of at least 20 percent.

81. The process as recited in claim 78, wherein said anti-mitotic compound has a positive magnetic susceptibility of at least 5,000×

10<sup>−

6</sup> cgs.

82. The process as recited in claim 78, wherein said anti-mitotic compound is comprised of at least 10 carbon atoms.

83. The process as recited in claim 78, wherein said inorganic atom is radioactive.

84. The process as recited in claim 78, wherein said inorganic atom has a magnetic moment of at least 1.0 bohr magnetron.

85. The process as recited in claim 78, wherein said anti-mitotic compound has a mitotic index factor of at least about 50 percent.

86. The process as recited in claim 78, wherein said anti-mitotic compound has a positive magnetic susceptibility of at least 10,000×

10<sup>−

6</sup> cgs.

87. The process as recited in claim 78, wherein said inorganic atom has a magnetic moment of at least 2.0 bohr magnetrons.

88. A therapeutic construct comprised of a tubulin molecule bound to the anti-mitotic compound recited in claim 1.

89. The therapeutic construct as recited in claim 88, wherein said tubulin molecule is a beta-tubulin molecule.

90. The therapeutic construct as recited in claim 88, wherein said anti-mitotic compound has a mitotic index factor of at least 20 percent.

91. The therapeutic construct as recited in claim 88, wherein anti-mitotic compound has a positive magnetic susceptibility of at least 5,000×

10<sup>−

6</sup> cgs.

92. The therapeutic construct as recited in claim 88, wherein said anti-mitotic compound is comprised of at least 10 carbon atoms.

93. The therapeutic construct as recited in claim 88, wherein said inorganic atom is radioactive.

94. The therapeutic construct as recited in claim 88, wherein said inorganic atom has a magnetic moment of at least 1.0 bohr magnetron.

95. The therapeutic construct as recited in claim 88, wherein said anti-mitotic compound has a mitotic index factor of at least about 50 percent.

96. The therapeutic construct as recited in claim 88, wherein said anti-mitotic compound has a positive magnetic susceptibility of at least 10,000×

10<sup>−

6</sup> cgs.

97. The therapeutic construct as recited in claim 88, wherein said inorganic atom has a magnetic moment of at least 2.0 bohr magnetrons.