Temporary embolization using inverse thermosensitive polymers

• US 20050008610A1
• Filed: 03/05/2004
• Published: 01/13/2005
• Est. Priority Date: 03/24/2003
• Status: Abandoned Application

• Current Assignee: Pluromed, Inc. (Sanofi )
• Original Assignee: Pluromed, Inc. (Sanofi )
• Inventors: Raymond, Jean, Schwarz, Alexander
• Application Number:
  US10/794,804
• Publication Number:
  US 20050008610A1
• Time in Patent Office: Days
• US Class Current: 424/78.100
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/408 Virucides, spermicides
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/44 Radioisotopes, radionuclides
• CPC Class Codes: A61L 2300/442 Colorants, dyes
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices artificial blood vessels A61L27/507
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides

Abstract

One aspect of the present invention relates to methods of embolizing a vascular site in a mammal comprising introducing into the vasculature of a mammal a composition comprising an inverse thermosensitive polymer, wherein said inverse thermosensitive polymer gels in said vasculature, which composition may be injected through a small catheter, and which compositions gel at or below body temperature. In certain embodiments of the methods of embolization, said composition further comprises a marker molecule, such as a dye, radiopaque, or an MRI-visible compound.

Claims

1. A method of temporarily embolizing a vascular site in a mammal, comprising the step of:

introducing into the vasculature of a mammal a composition comprising an inverse thermosensitive polymer, wherein said inverse thermosensitive polymer gels in said vasculature, thereby temporarily embolizing a vascular site of said mammal.

2. The method of claim 1, wherein said mammal is a human.

3. The method of claim 1, wherein the transition temperature of said inverse thermosensitive polymer is between about 10 C. and about 40 C.

4. The method of claim 1, wherein the volume of the inverse thermosensitive polymer between its transition temperature and physiological temperature is between about 80% and about 150% of the volume of the inverse thermosensitive polymer below its transition temperature.

5. The method of claim 1, wherein said inverse thermosensitive polymer is a block copolymer, random copolymer, graft polymer, or branched copolymer.

6. The method of claim 1, wherein said inverse thermosensitive polymer is a block copolymer.

7. The method of claim 1, wherein said inverse thermosensitive polymer is a polyoxyalkylene block copolymer.

8. The method of claim 1, wherein said inverse thermosensitive polymer is a poloxamer or poloxamine.

9. The method of claim 1, wherein said inverse thermosensitive polymer is a poloxamer.

10. The method of claim 1, wherein said inverse thermosensitive polymer is poloxamer 407, poloxamer 338, poloxamer 188, poloxamine 1107 or poloxamine 1307.

11. The method of claim 1, wherein said inverse thermosensitive polymer is poloxamer 407 or poloxamer 338.

12. The method of claim 1, wherein the transition temperature of said inverse thermosensitive polymer is between about 10 C. and about 40 C.;

and the volume of the inverse thermosensitive polymer between its transition temperature and physiological temperature is between about 80% and about 150% of the volume of the inverse thermosensitive polymer below its transition temperature.

13. The method of claim 1, wherein the transition temperature of said inverse thermosensitive polymer is between about 10 C. and about 40 C.;

the volume of the inverse thermosensitive polymer between its transition temperature and physiological temperature is between about 80% and about 150% of the volume of the inverse thermosensitive polymer below its transition temperature; and

said inverse thermosensitive polymer is a block copolymer, random copolymer, graft polymer, or branched copolymer.

14. The method of claim 1, wherein the transition temperature of said inverse thermosensitive polymer is between about 10 C. and about 40 C.;

the volume of the inverse thermosensitive polymer between its transition temperature and physiological temperature is between about 80% and about 150% of the volume of the inverse thermosensitive polymer below its transition temperature; and

said inverse thermosensitive polymer is a block copolymer.

15. The method of claim 1, wherein the transition temperature of said inverse thermosensitive polymer is between about 10 C. and about 40 C.;

the volume of the inverse thermosensitive polymer between its transition temperature and physiological temperature is between about 80% and about 150% of the volume of the inverse thermosensitive polymer below its transition temperature; and

said inverse thermosensitive polymer is a polyoxyalkylene block copolymer.

16. The method of claim 1, wherein the transition temperature of said inverse thermosensitive polymer is between about 10 C. and about 40 C.;

the volume of the inverse thermosensitive polymer between its transition temperature and physiological temperature is between about 80% and about 150% of the volume of the inverse thermosensitive polymer below its transition temperature; and

said inverse thermosensitive polymer is a poloxamer or poloxamine.

17. The method of claim 1, wherein the transition temperature of said inverse thermosensitive polymer is between about 10 C. and about 40 C.;

the volume of the inverse thermosensitive polymer between its transition temperature and physiological temperature is between about 80% and about 150% of the volume of the inverse thermosensitive polymer below its transition temperature; and

said inverse thermosensitive polymer is a poloxamer.

18. The method of claim 1, 2, 8, 9, 10, or 11, wherein said composition comprising an inverse thermosensitive polymer is introduced into the vasculature of said mammal using a catheter.

19. The method of claim 1, 2, 8, 9, 10, or 11, wherein said vascular site is proximal to a surgical incision, hemorrhage, cancerous tissue, uterine fibroid, tumor, or organ.

20. The method of claim 1, 2, 8, 9, 10, or 11, wherein said composition comprising an inverse thermosensitive polymer embolizes said vascular site for less than about twelve hours.

21. The method of claim 1, 2, 8, 9, 10, or 11, wherein said composition comprising an inverse thermosensitive polymer embolizes said vascular site for less than about nine hours.

22. The method of claim 1, 2, 8, 9, 10, or 11, wherein said vascular site is embolized for less than about six hours.

23. The method of claim 1, 2, 8, 9, 10, or 11, wherein said vascular site is embolized for less than about three hours.

24. The method of claim 1, 2, 8, 9, 10, or 11, wherein said vascular site is embolized for less than about two hours.

25. The method of claim 1, 2, 8, 9, 10, or 11, wherein said vascular site is embolized for less than about one hour.

26. The method of claim 1, 2, 8, 9, 10, or 11, wherein said vascular site is embolized for less than about thirty minutes.

27. The method of claim 1, 2, 8, 9, 10, or 11, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.5 to about 1.0.

28. The method of claim 1, 2, 8, 9, 10, or 11, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.2 to about 1.0.

29. The method of claim 1, 2, 8, 9, 10, or 11, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.1 to about 1.0.

30. The method of claim 1, wherein said composition comprising an inverse thermosensitive polymer further comprises a contrast-enhancing agent.

31. The method of claim 30, wherein said contrast-enhancing agent is selected from the group consisting of radiopaque materials, paramagnetic materials, heavy atoms, transition metals, lanthanides, actinides, dyes, and radionuclide-containing materials.

32. The method of claim 1, wherein said composition comprising an inverse thermosensitive polymer further comprises a biologically active agent.

33. The method of claim 32, wherein the biologically active agent is selected from the group consisting of antiinflammatories, antibiotics, antimicrobials, antivirals, analgesics, antiproliferatives, and chemotherapeutics.