Method and kit for inducing hypoxia in tumors through the use of a magnetic fluid

• US 7,448,389 B1
• Filed: 10/10/2003
• Issued: 11/11/2008
• Est. Priority Date: 10/10/2003
• Status: Expired due to Fees

• Current Assignee: Materials Modification Inc.
• Original Assignee: Materials Modification Inc.
• Inventors: Kotha, Sanjay, Sudarshan, Tirumalai S.
• Primary Examiner(s): Gilbert; Samuel G
• Application Number:
  US10/681,899
• Time in Patent Office: 1,859 Days
• Field of Search: 600 1- 15, 128897-899
• US Class Current: 128/898
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 33/242 Gold; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: A61K 33/44 Elemental carbon, e.g. charcoal, carbon black
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting

Abstract

A method and kit for inducing hypoxia in tumors includes impeding oxygen supply to non-hypoxic cells in a subject in need thereof by using a magnetic fluid.

Claims

1. A method of inducing hypoxia in a non-hypoxic region of a tumor, comprising the steps of:

a) administering a magnetic fluid in a subject in need thereof through a blood vessel feeding a tumor; and

b) applying a magnetic field adjacent the tumor to join a plurality of particles in the magnetic fluid to form a blockage in the blood vessel thereby impeding the flow of blood to the tumor.

2. The method of claim 1, wherein:

the magnetic fluid in step a) is delivered through a catheter or by injection.

3. The method of claim 1, wherein:

the magnetic field in step b) is applied by an internal micromagnet, an external rare earth magnet, or an external electromagnet.

4. The method of claim 1, wherein:

the magnetic fluid comprises core particles of a magnetic material.

5. The method of claim 4, wherein:

the core particles comprise coated particles.

6. The method of claim 4, wherein:

the core particles have an average diameter of about 1 nm to 20 μ

m.

7. The method of claim 6, wherein:

the core particles have an average diameter of about 10 nm to 5 μ

m.

8. The method of claim 7, wherein:

the core particles have an average diameter of about 10 nm to 1,000 nm.

9. The method of claim 6, wherein:

the core particles are dispersed in a carrier fluid.

10. The method of claim 9, wherein:

the carrier fluid comprises a water-based carrier fluid.

11. The method of claim 9, wherein:

the carrier fluid is selected from the group consisting of water, Ringer'"'"'s solution, normal saline, sugar solution, blood plasma, and a combination thereof.

12. The method of claim 9, wherein:

the fraction of the core particles is about 1-90%.

13. The method of claim 6, wherein:

the core particles comprise a general shape selected from the group consisting of spherical, needle-like, cubic, irregular, cylindrical, diamond, oval, and a combination thereof.

14. The method of claim 4, wherein:

the magnetic material is selected from the group consisting of iron, iron oxide, cobalt, cobalt oxide, nickel, nickel oxide, an alloy, and a combination thereof.

15. The method of claim 4, wherein:

the core particles comprise a coating of a surfactant.

16. The method of claim 15, wherein:

the surfactant is selected from the group consisting of polyethylene oxide, dextran, polyoxypropylene-polyoxyethylene block copolymer, and a combination thereof.

17. The method of claim 4, wherein:

the core particles comprise a coating selected from the group consisting of a ceramic material, a metallic material, a polymer material, and a combination thereof.

18. The method of claim 17, wherein:

the coating is selected from the group consisting of silica, gold, silver, platinum, steel, cobalt, carbon, polyethylene glycol, dextran, polyoxyethylene sorbitol ester, sorbitol, mannitol, and a combination thereof.

19. The method of claim 4, wherein:

the core particles comprise first and second successive coatings.

20. The method of claim 19, wherein:

the first coating comprises a coating of a surfactant; and

the second coating comprises a coating of a material selected from the group consisting of a ceramic material, a metallic material, a polymer material, and a combination thereof.

21. The method of claim 20, wherein:

the surfactant is selected from the group consisting of polyethylene oxide, dextran, polyoxypropylene-polyoxyethylene block copolymer, and a combination thereof.

22. The method of claim 21, wherein:

the second coating is selected from the group consisting of silica, gold, silver, platinum, steel, cobalt, carbon, polyethylene glycol, dextran, polyoxyethylene sorbitol ester, sorbitol, mannitol, and a combination thereof.

23. A method of treating a tumor, comprising the steps of:

a) administering a magnetic fluid in a subject in need thereof through a blood vessel feeding a tumor;

b) applying a magnetic field adjacent the tumor to join a plurality of particles in the magnetic fluid to form a blockage in the blood vessel thereby impeding the flow of blood to the tumor; and

c) continuing with step b) for a sufficient time to induce hypoxia in a non-hypoxic region of the tumor.

24. The method of claim 23, further comprising the step of:

d) administering a hypoxic drug prior to or after step a), or substantially simultaneously therewith.

25. The method of claim 24, wherein:

the hypoxic drug is selected from the group consisting of AQ4N, mitomycin C, porfiromycin, and tirapazamine.

26. The method of claim 24, wherein:

the hypoxic drug is administered through a catheter, by injection, or intravenously.

27. The method of claim 23, wherein:

the magnetic fluid is delivered through a catheter or by injection.

28. The method of claim 23, wherein:

the magnetic field is applied by an internal micromagnet, an external rare earth magnet, or an external electromagnet.

29. The method of claim 23, wherein:

the magnetic fluid comprises core particles of a magnetic material.

30. The method of claim 29, wherein:

the core particles comprise coated particles.

31. The method of claim 29, wherein:

the core particles have an average diameter of about 1 nm to 20 μ

m.

32. The method of claim 31, wherein:

the core particles have an average diameter of about 10 nm to 5 μ

m.

33. The method of claim 32, wherein:

the core particles have an average diameter of about 10 nm to 1,000 nm.

34. The method of claim 31, wherein:

the core particles are dispersed in a carrier fluid.

35. The method of claim 34, wherein:

the carrier fluid comprises a water-based carrier fluid.

36. The method of claim 34, wherein:

the carrier fluid is selected from the group consisting of water, Ringer'"'"'s solution, normal saline, sugar solution, blood plasma, and a combination thereof.

37. The method of claim 34, wherein:

the fraction of the core particles is about 1-90%.

38. The method of claim 31, wherein:

the core particles comprise a general shape selected from the group consisting of spherical, needle-like, cubic, irregular, cylindrical, diamond, oval, and a combination thereof.

39. The method of claim 29, wherein:

the magnetic material is selected from the group consisting of iron, iron oxide, cobalt, cobalt oxide, nickel, nickel oxide, an alloy, and a combination thereof.

40. The method of claim 29, wherein:

the core particles comprise a coating of a surfactant.

41. The method of claim 40, wherein:

the surfactant is selected from the group consisting of polyethylene oxide, dextran, polyoxyethylene sorbitol ester, and a combination thereof.

42. The method of claim 29, wherein:

the core particles comprise a coating selected from the group consisting of a ceramic material, a metallic material, a polymer material, and a combination thereof.

43. The method of claim 42, wherein:

the coating is selected from the group consisting of silica, gold, silver, platinum, steel, cobalt, carbon, polyethylene glycol, dextran, polyoxyethylene sorbitol ester, sorbitol, mannitol, and a combination thereof.

44. The method of claim 29, wherein:

the core particles comprise first and second successive coatings.

45. The method of claim 44, wherein:

the first coating comprises a coating of a surfactant; and

the second coating comprises a coating of a material selected from the group consisting of a ceramic material, a metallic material, a polymer material, and a combination thereof.

46. The method of claim 45, wherein:

the surfactant is selected from the group consisting of polyethylene oxide, dextran, polyoxypropylene-polyoxyethylene block copolymer, and a combination thereof.

47. The method of claim 46, wherein:

the second coating is selected from the group consisting of silica, gold, silver, platinum, steel, cobalt, carbon, polyethylene glycol, dextran, polyoxyethylene sorbitol ester, sorbitol, mannitol, and a combination thereof.