HYDROGEL FILAMENTS FOR BIOMEDICAL USES

• US 20090164013A1
• Filed: 12/19/2008
• Published: 06/25/2009
• Est. Priority Date: 12/21/2007
• Status: Active Grant

• Current Assignee: Microvention Incorporated (Terumo Corporation)
• Original Assignee: Microvention Incorporated (Terumo Corporation)
• Inventors: Keeley, Edward Michael, Tran, Terrance T., Cruise, Gregory M., Constant, Michael J.
• Granted Patent: US 8,470,035 B2
• Time in Patent Office: Days
• US Class Current: 623/11.110
• CPC Class Codes: A61B 17/12113 within an aneurysm
• CPC Class Codes: A61B 17/12181 formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable or resorptive
• CPC Class Codes: A61B 2017/1205 Introduction devices
• CPC Class Codes: A61B 2090/3966 Radiopaque markers visible in an X-ray image
• CPC Class Codes: A61B 90/39 Markers, e.g. radio-opaque or breast lesions markers
• CPC Class Codes: A61K 49/0404 containing barium sulfate
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• 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 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• 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 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: C08L 39/06 Homopolymers or copolymers of N-vinyl-pyrrolidones
• 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 difunctional, low molecular weight ethylenically unsaturated shapeable macromer;

an ethylenically unsaturated monomer; and

a visualization agent,

wherein said device contains no support members.

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 hydrogel is environmentally-responsive.

4. The device according to claim 1 wherein said macromer comprises polyethylene glycol, propylene glycol, poly(tetramethylene oxide), poly(ethylene glycol) diacrylamide, poly(ethylene glycol) diacrylate, poly(ethylene glycol) dimethacrylate, derivatives thereof, or combinations thereof.

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

6. The device according to claim 1 wherein said 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 visualization agent comprises an aromatic ring having a single unsaturation point and at least one iodine atom.

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

9. The device according to claim 1 wherein said ethylenically unsaturated monomer and said visualization element comprise 2,4,6-triiodophenyl penta-4-enoate, 5-acrylamido-2,4,6-triiodo-n,n′

-bis-(2,3 dihydroxypropyl) isophthalamide, derivatives thereof, or combinations thereof.

10. The device according to claim 1 wherein said macromer and said 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.

11. The device according to claim 1 wherein said ionizable functional groups comprise basic groups or acidic groups.

12. The device according to claim 11 wherein said ionizable functional groups comprise amine groups, derivatives thereof, or combinations thereof.

13. The device according to claim 11 wherein said acidic groups comprise a carboxylic acid, derivatives thereof, or combinations thereof.

14. The device according to claim 1 wherein said hydrogel is substantially free of acrylamide.

15. The device according to claim 1 wherein said hydrogel is substantially non-bioresorbable.

16. The device according to claim 1 wherein said hydrogel is bioresorbable.

17. A method for preparing device for implantation in an animal comprising:

a) combining a difunctional, low molecular weight ethylenically unsaturated shapeable macromer, an ethylenically unsaturated monomer, a visualization agent, and a solvent to prepare a prepolymer solution; and

b) treating said prepolymer solution to prepare hydrogel that is expansible at physiological conditions.

18. The method according to claim 17 wherein said solvent comprises water, dichloromethane, acetone, isopropyl alcohol, ethanol or combinations thereof.

19. The method according to claim 17 wherein said difunctional, low molecular weight ethylenically unsaturated shapeable macromer has a molecular weight of about 100 grams/mole to about 5000 grams/mole.

20. The method according to claim 17 wherein said ethylenically unsaturated monomer comprises ionizable functional groups.

21. The method according to claim 17 wherein said solvent comprises about 20% w/w to about 80% w/w of the prepolymer solution.

22. The method according to claim 17 wherein said monomer comprises about 40% to about 80% by weight of the prepolymer solution.

23. The method according to claim 17 wherein further comprising the step of adding a second an ethylenically unsaturated monomer to said prepolymer solution.

24. The method according to claim 17 wherein said ionizable functional groups comprise basic groups and said treating step comprises de-protonating said basic groups at pHs greater than the pKa or protonating said basic groups at pHs less than the pKa of said basic groups.

25. The method according to claim 17 wherein said ionizable functional groups comprise acidic groups and said treating step comprises protonating said acidic groups at pHs less than the pKa or de-protonating said acidic groups at pHs greater than the pKa of said acidic groups.

26. A device for implantation in an animal comprising:

a difunctional, low molecular weight ethylenically unsaturated shapeable macromer with a molecular weight of about 100 grams/mole to about 5000 grams/mole;

an ethylenically unsaturated monomer; and

a visualization agent, wherein said device contains no metallic support members.