Injectable hydrogel filaments for biomedical uses

• US 9,114,200 B2
• Filed: 09/24/2010
• Issued: 08/25/2015
• Est. Priority Date: 09/24/2009
• Status: Active Grant

• Current Assignee: Microvention Incorporated (Terumo Corporation)
• Original Assignee: Microvention Incorporated (Terumo Corporation)
• Inventors: Constant, Michael J., Cruise, Gregory M., Keeley, E. Michael, Berenstein, Alejandro
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US12/890,540
• Publication Number:
  US 20110212178A1
• Time in Patent Office: 1,796 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Described herein are apparatus, compositions, systems and associated methods to occlude structures and malformations with radiopaque hydrogel filaments with delayed controlled rates of expansion permitting the repositioning of the device once inside the structure or malformation. Further described is a device for implantation in an animal comprising a difunctional, low molecular weight ethylenically unsaturated shapeable macromer; an ethylenically unsaturated monomer; and a radiopaque element, wherein said device contains no support members. Methods of forming such devices are also disclosed.

Claims

1. A device for implantation comprising:

a filament including about 30% of a difunctional, low molecular weight ethylenically unsaturated shapeable poly(tetramethylene oxide) macromer;

a first ethylenically unsaturated monomer, wherein said first monomer is ionizable;

a second ethylenically unsaturated monomer; and

a visualization agent,

wherein said device contains no support members and said filament has a bending resistance between about 0.5 mg and 0.1 mg.

2. The device according to claim 1 wherein said macromer has a molecular weight of about 100 grams/mole to about 5000 grams/mole.

3. The device according to claim 1 wherein said filament is environmentally-responsive.

4. The device according to claim 1 wherein said macromer comprises poly(tetramethylene oxide) diacrylate.

5. The device according to claim 1 wherein said first ethylenically unsaturated monomer comprises one or more ionizable functional groups.

6. The device according to claim 1 wherein said second ethylenically unsaturated monomer comprises N,N′

-methylenebisacrylamide, N-vinyl pyrrolidinone, 2-hydroxyethyl methacrylate, derivatives thereof, or combinations thereof.

7. The device according to claim 1 wherein said macromer, said first monomer, and said second monomer are crosslinked with N,N,N′

,N′

-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2′

-azobis(2-methylpropionamidine) dihydrochloride, derivatives thereof, or combinations thereof.

8. The device according to claim 1 wherein said visualization agent comprises 48.6% w/w barium sulfate.

9. The device according to claim 1 wherein said visualization agent comprises 45.1% w/w barium sulfate.

10. The device according to claim 1 wherein said visualization agent comprises 59% barium sulfate after drying.

11. The device according to claim 1 comprising about 7% hydroxyethyl methacrylate, about 3% acrylic acid, about 1% bisacrylamide, and about 59% barium sulfate after drying.

12. The device according to claim 1 wherein said visualization agent comprises 56% barium sulfate after drying.

13. The device according to claim 1 comprising about 8% hydroxyethyl methacrylate, about 3% acrylic acid, and about 56% barium sulfate after drying.

14. The device according to claim 1 wherein said visualization agent comprises gadolinium or iron oxide.

15. The device according to claim 1 wherein said visualization element comprise barium.

16. The device according to claim 7 wherein said cross-linker comprises N,N′

-methylenebisacrylamide.

17. The device according to claim 5 wherein said ionizable functional groups comprise basic groups or acidic groups.

18. The device according to claim 17 wherein said basic groups comprise amine groups, derivatives thereof, or combinations thereof.

19. The device according to claim 17 wherein said acidic groups comprise a carboxylic acid, derivatives thereof, or combinations thereof.

20. The device according to claim 1 wherein said filament is substantially free of acrylamide.

21. The device according to claim 1 wherein said filament is substantially non-bioresorbable.

22. The device according to claim 1 wherein said filament is bioresorbable.

23. A device for implantation comprising:

a filament including about 33% of a difunctional, low molecular weight ethylenically unsaturated shapeable poly(tetramethylene oxide) macromer;

a first ethylenically unsaturated monomer, wherein said first monomer is ionizable;

a second ethylenically unsaturated monomer; and

a visualization agent,

wherein said device contains no support members and said filament has a bending resistance between about 0.5 mg and 0.1 mg.

24. The device according to claim 23 wherein said macromer has a molecular weight of about 100 grams/mole to about 5000 grams/mole.

25. The device according to claim 23 wherein said filament is environmentally-responsive.

26. The device according to claim 23 wherein said macromer comprises poly(tetramethylene oxide) diacrylate.

27. The device according to claim 23 wherein said first ethylenically unsaturated monomer comprises one or more ionizable functional groups.

28. The device according to claim 23 wherein said second ethylenically unsaturated monomer comprises N,N′

-methylenebisacrylamide, N-vinyl pyrrolidinone, 2-hydroxyethyl methacrylate, derivatives thereof, or combinations thereof.

29. The device according to claim 23 wherein said visualization agent comprises 48.6% w/w barium sulfate.

30. The device according to claim 23 wherein said visualization agent comprises 45.1% w/w barium sulfate.

31. The device according to claim 23 wherein said visualization agent comprises 59% barium sulfate after drying.

32. The device according to claim 23 comprising about 7% hydroxyethyl methacrylate, about 3% acrylic acid, about 1% bisacrylamide, and about 59% barium sulfate after drying.

33. The device according to claim 23 wherein said visualization agent comprises 56% barium sulfate after drying.

34. The device according to claim 23 comprising about 8% hydroxyethyl methacrylate, about 3% acrylic acid, and about 56% barium sulfate after drying.

35. The device according to claim 23 wherein said visualization agent comprises gadolinium or iron oxide.

36. The device according to claim 23 wherein said visualization element comprises barium.

37. The device according to claim 23 wherein said macromer, said first monomer, and said second monomer are crosslinked with N,N,N′

,N′

-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2′

-azobis(2-methylpropionamidine) dihydrochloride, derivatives thereof, or combinations thereof.

38. The device according to claim 37 wherein said cross-linker comprises N,N′

-methylenebisacrylamide.

39. The device according to claim 27 wherein said ionizable functional groups comprise basic groups or acidic groups.

40. The device according to claim 39 wherein said basic groups comprise amine groups, derivatives thereof, or combinations thereof.

41. The device according to claim 39 wherein said acidic groups comprise a carboxylic acid, derivatives thereof, or combinations thereof.

42. The device according to claim 23 wherein said filament is substantially free of acrylamide.

43. The device according to claim 23 wherein said filament is substantially non-bioresorbable.

44. The device according to claim 23 wherein said filament is bioresorbable.