Radioactive embolizing compositions

• US 6,015,541 A
• Filed: 11/03/1997
• Issued: 01/18/2000
• Est. Priority Date: 11/03/1997
• Status: Expired due to Term

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Micro Therapeutics, Inc. (Medtronic Plc)
• Inventors: Wallace, George, Greff, Richard J.
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Hartley, Michael G.
• Application Number:
  US08/962,819
• Time in Patent Office: 806 Days
• Field of Search: 424/1.25, 424/1.11, 424/1.13, 424/1.29, 424/1.33, 600/3, 600/4, 600/7, 600/8, 604/264, 524/916, 252/625, 252/634, 252/315.01, 514/944
• US Class Current: 424/1.25
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• CPC Class Codes: A61K 51/06 Macromolecular compounds , carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules peptides, proteins, polyamino acids A61K51/08; antibodies A61K51/10
• CPC Class Codes: A61K 51/1217 Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Disclosed are novel radioactive compositions which are particularly suited for treating solid mass tumors via catheter delivery.

Claims

1. A composition suitable for treating a solid mass tumor in a mammal which composition comprises:

(a) a non-crosslinked, biocompatible, non-biodegradable polymer which polymer is insoluble in blood;

(b) a biocompatible solvent which is an organic material liquid at least at body temperature of the mammal and which solubilizes said polymer with the proviso that when said solvent comprises water, the amount of water employed is sufficiently small that the dissolved polymer precipitates upon contact with the blood; and

(c) from about 0.1 to about 25 weight percent of a water insoluble radioisotope having from a radioactive content of from about 0.5 microcurie to about 100 millicuries with the proviso that when theradioisotope is either water soluble or water reactable, said isotope is used as a water insoluble salt.

2. The composition according to claim 1 wherein said biocompatible solvent is selected from the group consisting of dimethylsulfoxide, ethanol and acetone.

3. The composition according to claim 2 wherein said biocompatible solvent is dimethylsulfoxide.

4. The composition according to claim 1 wherein said non-biodegradable biocompatible polymer is selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid, and mixtures thereof.

5. The composition according to claim 4 wherein said non-biodegradable biocompatible polymer is a copolymer of ethylene and vinyl alcohol.

6. The composition according to claim 1 wherein said radioisotope is selected from the group consisting of ⁹⁰ yttrium, ¹⁹² iridium, ¹⁹⁸ gold, ¹²⁵ iodine, ¹³⁷ cesium, ⁶⁰ cobalt, ⁵⁵ cobalt, ⁵⁶ cobalt, ⁵⁷ cobalt, ⁵⁷ magnesium, ⁵⁵ iron, ³² phosphorus, ⁹⁰ strontium, ⁸¹ rubidium, ²⁰⁶ bismuth, ⁶⁷ gallium, ⁷⁷ bromine, ¹²⁹ cesium, ⁷³ selenium, ⁷² selenium, ⁷² arsenic, ¹⁰³ palladium, ²⁰³ lead, ¹¹¹ indium, ⁵² iron, ¹⁶⁷ thulium, ⁵⁷ nickel, ⁶² zinc, ⁶¹ copper, ²⁰¹ thallium, and ¹²³ iodine.

7. The composition according to claim 1 which further comprises a non-radioactive contrast agent.

8. The composition according to claim 7 wherein said non-radioactive contrast agent is water soluble.

9. The composition according to claim 8 wherein said water soluble non-radioactive contrast agent is selected from the group consisting of metrizamide, iopamidol, iothalamate sodium, iodomide sodium, and meglumine.

10. The composition according to claim 7 wherein said non-radioactive contrast agent is water insoluble.

11. The composition according to claim 10 wherein said water insoluble contrast agent is tantalum, tantalum oxide, barium sulfate, tungsten, gold and platinum.

12. A method for embolizing a blood vessel leading to or in a solid mass tumor in a mammal and causing necrosis to a portion of said solid mass tumor which method comprises:

(a) identifying a blood vessel in said mammal which leads to or is in the solid mass tumor;

(b) injecting a sufficient amount of an embolic composition comprising;

(i) a non-crosslinked, biocompatible, non-biodegradable polymer which polymer is insoluble in blood;

(ii) a biocompatible solvent which is an organic material liquid at least at body temperature of the mammal and which solubilizes said polymer with the proviso that when said solvent comprises water, the amount of water employed is sufficiently small that the dissolved polymer precipitates upon contact with the blood; and

(iii) from about 0.1 to about 25 weight percent of a water insoluble radioiotope having from a radioactive content of from about 0.5 microcurie to about 100 millicuries with the proviso that when the radioisotope is either water soluble or water reactable, said isotope is used as a water insoluble salt

into said blood vessel under conditions wherein a precipitate is formed which embolizes the blood vessel and further wherein the radioisotope is employed in an amount effective to cause necrosis of at least a portion of said tumor.

13. The method according to claim 12 wherein said biocompatible solvent is selected from the group consisting of dimethylsulfoxide, ethanol and acetone.

14. The method according to claim 13 wherein said biocompatible solvent is dimethylsulfoxide.

15. The method according to claim 12 wherein said non-biodegradable biocompatible polymer is selected from the group consisting of cellulose acetates, ethylene vinyl alcohol copolymers, hydrogels, polyacrylonitrile, polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymers of urethane/carbonate, copolymers of styrene/maleic acid, and mixtures thereof.

16. The method according to claim 15 wherein said non-biodegradable biocompatible polymer is a copolymer of ethylene and vinyl alcohol.

17. The method according to claim 12 wherein said radioisotope is selected from the group consisting of ⁹⁰ yttrium, 192iridium, ¹⁹⁸ gold, ¹²⁵ iodine, ¹³⁷ cesium, ⁶⁰ cobalt, ⁵⁵ cobalt, ⁵⁶ cobalt, ⁵⁷ cobalt, ⁵⁷ magnesium, ⁵⁵ iron, ³² phosphorus, ⁹⁰ strontium, ⁸¹ rubidium, ²⁰⁶ bismuth, ⁶⁷ gallium, ⁷⁷ bromine, ¹²⁹ cesium, ⁷³ selenium, ⁷² selenium, ⁷² arsenic, ¹⁰³ palladium, ²⁰³ lead, ¹¹¹ indium, ⁵² iron, ¹⁶⁷ thulium, ⁵⁷ nickel, ⁶² zinc, ⁶¹ copper, ²⁰¹ thallium, and ¹²³ iodine.

18. The method according to claim 12 wherein said composition further comprises a non-radioactive contrast agent.

19. The method according to claim 17 wherein said non-radioactive contrast agent is water soluble.

20. The method according to claim 18 wherein said water soluble non-radioactive contrast agent is selected from the group consisting of metrizamide, iopamidol, iothalamate sodium, iodomide sodium, and meglumine.

21. The method according to claim 17 wherein said non-radioactive contrast agent is water insoluble.

22. The method according to claim 21 wherein said water insoluble contrast agent is tantalum, tantalum oxide, barium sulfate, tungsten, gold and platinum.

23. A method for causing necrosis to a portion of a solid mass tumor which method comprises:

(a) identifying a solid mass tumor in a mammal;

(b) injecting a sufficient amount of an embolic composition comprising;

(i) a non-crosslinked, biocompatible, non-biodegradable polymer which polymer is insoluble in blood;

(ii) a biocompatible solvent which is an organic material liquid at least at body temperature of the mammal and which solubilizes said polymer with the proviso that when said solvent comprises water, the amount of water employed is sufficiently small that the dissolved polymer precipitates upon contact with the blood; and

(iii) from about 0.1 to about 25 weight percent of a water insoluble radioisotope having from a radioactive content of from about 0.5 microcurie to about 100 millicuries with the proviso that when the radioisotope is either water soluble or water reactable, said isotope is used as a water insoluble salt

into said tumor under conditions wherein a precipitate is formed wherein the radioisotope is employed in an amount effective to cause necrosis of at least a portion of said tumor.