Water-soluble compound

• US 20060147371A1
• Filed: 02/23/2005
• Published: 07/06/2006
• Est. Priority Date: 10/31/2003
• Status: Abandoned Application

• Current Assignee: Technology Innovations, LLC
• Original Assignee: Technology Innovations, LLC
• Inventors: Greenwald, Howard J., Goss, Kendrick, Tuszynski, Jack A., Curry, Stephen H.
• Application Number:
  US11/063,439
• Publication Number:
  US 20060147371A1
• Time in Patent Office: Days
• US Class Current: 424/1.110
• 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 composition of matter comprised of a substrate comprised of a biologically active substrate and a magnetic moiety wherein:

a. said biologically active substrate is an anti-microtubule agent, and

b. said magnetic moiety is covalently bound to said biologically active substrate.

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

3. The composition of matter as recited in claim 2, wherein said substrate has a mitotic index factor of at least about 30 percent.

4. The composition of matter as recited in claim 3, wherein said substrate has a mitotic index factor of at least about 50 percent.

5. The composition of matter as recited in claim 1, wherein said magnetic moiety is paramagnetic.

6. The composition of matter as recited in claim 5, wherein said magnetic moiety is comprised of a nitroxide.

7. The composition of matter as recited in claim 1, wherein said magnetic moiety is comprised of a metallic atom.

8. The composition of matter as recited in claim 7, wherein said magnetic moiety is ferromagnetic.

9. The composition of matter as recited in claim 7, wherein said metallic atom has a positive magnetic susceptibility of at least 2×

10<sup>−

4</sup> cgs.

10. The composition of matter as recited in claim 9, wherein said metallic atom is selected from the group consisting of cerium, cobalt, dysprosium, europium, gadolinium, manganese, palladium, plutonium, praseodymium, samarium, technetium, and thulium.

11. The composition of matter as recited in claim 7, wherein said metallic atom is selected from the group consisting of cerium, cobalt, dysprosium, europium, gadolinium, manganese, palladium, plutonium, praseodymium, samarium, technetium, thulium, iron, and gallium.

12. The composition of matter as recited in claim 11, wherein said metallic atom is a radioactive isotope.

13. The composition of matter as recited in claim 12, wherein said metallic atom is selected from the group consisting of cerium, cobalt-53, cobalt-54, cobalt-55, cobalt-56, cobalt-57, cobalt-58, cobalt-59, cobalt-60, cobalt-61, cobalt-62, cobalt-63, gadolinium-146, manganese-50, iron-49, iron-51, iron-52, iron-53, iron-54, iron-57, iron-58, iron-59, iron-60, iron-61, and iron-62.

14. The composition of matter as recited in claim 9, wherein said substrate has a water solubility of at least about 10 microgram per milliliter.

15. The composition of matter as recited in claim 14, wherein said substrate has a water solubility of at least about 100 microgram per milliliter.

16. The composition of matter as recited in claim 15, wherein said substrate has a water solubility of at least about 500 microgram per milliliter.

17. The composition of matter as recited in claim 16, wherein said substrate has a water solubility of at least about 1000 microgram per milliliter.

18. The composition of matter as recited in claim 8, wherein said metallic atom is iron.

19. The composition of matter as recited in claim 18, wherein said iron is iron (III).

20. The composition of matter as recited in claim 8, wherein said metallic atom is gallium.

21. The composition of matter as recited in claim 19, wherein said magnetic moiety is further comprised of at least seven carbon atoms.

22. The composition of matter as recited in claim 9, wherein said substrate has a positive magnetic susceptibility of at least 1×

10<sup>−

3</sup> cgs.

23. The composition of matter as recited in claim 8, wherein said biologically active substrate is a taxane.

24. The composition of matter as recited in claim 23, wherein said taxane is a paclitaxel.

25. The composition of matter as recited in claim 24, wherein said paclitaxel is a 10-desacetyl paclitaxel.

26. The composition of matter as recited in claim 23, wherein said taxane is a docetaxel.

27. The composition of matter as recited in claim 23, wherein said magnetic moiety is a siderophore.

28. The composition of matter as recited in claim 27, wherein said siderophore is a catecholate.

29. The composition of matter as recited in claim 28, wherein said catecholate is an albomycin.

30. The composition of matter as recited in claim 28, wherein said catecholate is an agrobactin.

31. The composition of matter as recited In claim 28, wherein said catecholate is a enterobactin.

32. The composition of matter as recited in claim 27, wherein said siderophore is a hydroxamic acid.

33. The composition of matter as recited in claim 32, wherein said hydroxamic acid is a ferrichrome.

34. The composition of matter as recited in claim 32, wherein said hydroxamic acid is a ferricrocin.

35. The composition of matter as recited in claim 32, wherein said hydroxamic acid is an albomycin.

36. The composition of matter as recited in claim 32, wherein said hydroxamic acid is a ferrioxamine.

37. The composition of matter as recited in claim 32, wherein said hydroxamic acid is a rhodotorulic acid.

38. The composition of matter as recited in claim 32, wherein said hydroxamic acid is of the formula —

(CH₂)_m—

N(OH)—

C(O)—

(CH₂)_n—

(CH═

CH)_o—

CH₃ wherein;

a. m is an integer from 2 to 6,

b. n is selected from the group consisting of zero and a number from 1 to 22,

c. o is selected from the group consisting of zero and a number from 1 to 4, and

d. sum of m and o is no greater than 25.

39. The composition of matter as recited in claim 10, wherein said substrate is further comprised of a linker, wherein said linker is covalently bound to said magnetic moiety and said linker is covalently bound to said biologically active substrate.

40. The composition of matter as recited in claim 39, wherein said biologically active substrate is a taxane.

41. The composition of matter as recited in claim 40, wherein said linker is covalently bound to said biologically active substrate at a C-4 position of said taxane.

42. The composition of matter as recited in claim 40, wherein said linker is covalently bound to said biologically active substrate at a C-7 position of said taxane.

43. The composition of matter as recited in claim 40, wherein said linker is covalently bound to said biologically active substrate at a C-9 position of said taxane.

44. The composition of matter as recited in claim 40, wherein said linker is covalently bound to said biologically active substrate at a C-10 position of said taxane.

45. The composition of matter as recited in claim 40, wherein said linker is covalently bound to said biologically active substrate at a C-7 position and a C-9 position of said taxane.

46. The composition of matter as recited in claim 45, wherein said linker is comprised of an acetal.

47. The composition of matter as recited in claim 45, wherein said linker is comprised of a ketal.

48. A process for treating a disease comprising the steps of

a. administering a first substrate wherein

i. said first substrate is comprised of a first biologically active substrate and a first magnetic moiety wherein:

ii. said first biologically active substrate is an anti-mitotic agent, and

iii. said first magnetic moiety is covalently bound to said first biologically active substrate,

b. administering a second substrate wherein

i. said second substrate is comprised of a second biologically active substrate and a second magnetic moiety wherein;

ii. said second biologically active substrate is an anti-mitotic agent, and

iii. said second magnetic moiety is covalently bound to said second biologically active substrate,

c. wherein said first biologically active substrate and said second biologically active substrate are not the same substrate.

49. The process as recited in claim 48, wherein said first biologically active substrate is a taxane.

50. The process as recited in claim 49, wherein said first biologically active substrate has a mitotic index factor of at least about 10 percent.

51. The process as recited in claim 50, wherein said first biologically active substrate has a mitotic index factor of at least about 20 percent.

52. The process as recited in claim 51, wherein said first biologically active substrate has a mitotic index factor of at least about 50 percent.

53. The process as recited in claim 52, wherein said second biologically active substrate has a mitotic index factor of at least about 10 percent.

54. The process as recited in claim 53, wherein said second biologically active substrate has a mitotic index factor of at least about 20 percent.

55. The process as recited in claim 54, wherein said second biologically active substrate has a mitotic index factor of at least about 50 percent.

56. The process as recited in claim 55, wherein said first biologically active substrate has a molecular weight of at least 400 grams per mole.

57. The process as recited in claim 56, wherein said first biologically active substrate has a molecular weight of at least 500 grams per mole.

58. The process as recited in claim 57, wherein said first biologically active substrate has a molecular weight of at least 1000 grams per mole.

59. The process as recited in claim 58, wherein said first magnetic moiety has a positive magnetic susceptibility of at least 1×

10<sup>−

3</sup> cgs.

60. The process as recited in claim 59, wherein said first magnetic moiety has a positive magnetic susceptibility of at least 5×

10<sup>−

3</sup> cgs.

61. The process as recited in claim 60, wherein said first magnetic moiety has a positive magnetic susceptibility of at least 1×

10<sup>−

2</sup> cgs.

62. The process as recited in claim 60, wherein said taxane is comprised of an oxetane ring.

66. The composition of matter as recited in claim 54, wherein said biologically active substrate is an anti-microtubule agent.

63. A composition of matter comprised of a substrate comprised of a biologically active substrate and a magnetic moiety wherein said magnetic moiety is covalently bound to said biologically active substrate,

a. said magnetic moiety is comprised of a metallic atom,

b. said metallic atom has a positive magnetic susceptibility of at least 2×

10<sup>−

4</sup> cgs.

64. The composition of matter as recited in claim 63, wherein said biologically active substrate is a lectin.

65. The composition of matter as recited in claim 63, wherein said biologically active substrate is an anti-cancer agent.

67. A process for treating a disease comprising the steps of

a. administering a substrate to a patient wherein

i. said substrate is comprised of a biologically active substrate and a magnetic moiety wherein:

1. said biologically active substrate is an anti-microtubule agent, and

2. said magnetic moiety is covalently bound to said biologically active substrate, and

ii. said patient is comprised of a targeted tissue,

b. applying a magnetic field to said patient such that said magnetic field is focused upon said targeted tissue, and

c. said magnetic field acts upon said magnetic moiety and increases the concentration of said substrate at said targeted issue.

68. The process for treating a disease as recited in claim 67, wherein said magnetic field has a strength of at least about 6 Tesla.

69. The process for treating a disease as recited in claim 67, wherein said step of applying said magnetic field has a duration of at least about 30 minutes.

70. The process for treating a disease as recited in claim 69, wherein said step of applying said magnetic field is accomplished by a magnetic field generator, wherein said magnetic field generator is disposed within said patient.

71. The process for treating a disease as recited in claim 70, wherein said magnetic field generator is disposed substantially proximal to said targeted tissue.

72. The process for treating a disease as recited in claim 71, wherein said magnetic field generator is in telemetric communication with a controller, wherein said controller is disposed external to said patient.

73. The process for treating a disease as recited in claim 67, wherein said substrate is disposed within a drug delivery housing, wherein said drug delivery housing is disposed within said patient.

74. The process for treating a disease as recited in claim 73, wherein said drug delivery housing is operatively configured to release said substrate in response to ultrasonic energy from external to said patient.

75. The process for treating a disease as recited in claim 73, wherein said drug delivery housing is operatively configured to release said substrate in response to radio frequency energy from external to said patient.

76. The process for treating a disease as recited in claim 73, wherein said drug delivery housing is operatively configured to release said substrate in response to magnetic energy from external to said patient.

77. The process for treating a disease as recited in claim 73, wherein said drug delivery housing is a polymeric carrier.

78. The process for treating a disease as recited in claim 77, wherein said polymeric carrier is a drug eluting polymer.

79. The process for treating a disease as recited in claim 78, wherein said drug eluting polymer is silicon rubber.

80. The process for treating a disease as recited in claim 73, wherein said drug delivery housing is a pump.

81. The process for treating a disease as recited in claim 67, said step of administering said substrate to said patient is accomplished by an intravenous injection.

82. The process for treating a disease as recited in claim 67, said step of administering said substrate to said patient is accomplished by an intravenous drip over a period of at least 30 minutes.

83. The process for treating a disease as recited in claim 67, said step of administering said substrate to said patient is accomplished by a drug eluting stent.