Perfluorocyclobutane crosslinked hydrogels

• US 8,017,107 B2
• Filed: 12/21/2006
• Issued: 09/13/2011
• Est. Priority Date: 12/22/2005
• Status: Active Grant

• Current Assignee: Zimmer Incorporated (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Zimmer Incorporated (Zimmer Biomet Holdings, Inc.)
• Inventors: Zhang, Kai, Thomas, Brian
• Primary Examiner(s): FUBARA, BLESSING M
• Application Number:
  US11/614,389
• Publication Number:
  US 20070154429A1
• Time in Patent Office: 1,727 Days
• Field of Search: 424/70.11, 424/78.37, 525/199
• US Class Current: 424/70.11
• CPC Class Codes: A61F 2/32 for the hip
• CPC Class Codes: A61F 2/38 for elbows or knees
• CPC Class Codes: A61F 2/3804 for elbows
• CPC Class Codes: A61F 2/40 for shoulders
• CPC Class Codes: A61F 2/4202 for ankles
• CPC Class Codes: A61F 2/4241 for hands, e.g. fingers
• CPC Class Codes: A61F 2/4261 for wrists
• CPC Class Codes: A61F 2/44 for the spine, e.g. vertebrae, spinal discs
• CPC Class Codes: A61F 2002/30075 swellable, e.g. when wetted
• CPC Class Codes: A61F 2002/30125 elliptical or oval
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2210/0061 swellable
• CPC Class Codes: A61F 2230/0008 elliptical or oval
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61K 2800/57 Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/8135 Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an acyloxy radical of a saturated carboxylic acid, of carbonic acid or of a haloformic acid; Compositions of derivatives of such polymers, e.g. vinyl esters (polyvinylacetate)
• CPC Class Codes: A61K 8/8147 Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/8152 Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/8158 Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/8176 : Homopolymers of N-vinyl-pyrrolidones. Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/84 : obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 : Macromolecular materials
• CPC Class Codes: A61L 27/52 : Hydrogels or hydrocolloids
• CPC Class Codes: A61Q 11/00 : Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• CPC Class Codes: C08L 29/04 : Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids

Abstract

This invention provides water-swellable articles and hydrogels that contain a hydrophilic polymer and perfluorocyclobutane crosslinking segments. The perfluorocyclobutane crosslinking segments are covalently attached to the polymeric chains of the hydrophilic polymer so that the crosslinking segments chemically link the polymeric chains to each other. The present invention also provides a method of making a crosslinked hydrogel by first attaching one or more substituted aromatic trifluorovinyl or aromatic trifluorovinyl ether moieties to a hydrophilic polymer to form a modified polymer and then heating the modified polymer at an elevated temperature to form perfluorocyclobutane segments from the trifluorovinyl or trifluorovinyl ether moieties. These water-swellable articles and hydrogels may be used in biomedical and pharmaceutical applications and may be suitable for implanted joint repair materials such as an articulating or bearing surface in a hip, knee, spine, finger, ankle, elbow, wrist, or shoulder joint.

Claims

1. A perfluorocyclobutane crosslinked hydrogel comprising hydrophilic polymer chains crosslinked with at least one perfluorocyclobutane crosslinking segment, wherein the hydrophilic polymer is selected from the group consisting of poly(vinyl alcohol), poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(ethyleneimine), ethoxylated poly(ethyleneimine), poly(allylamine), poly(acrylamide), poly(acrylic acid), hydrolyzed poly(acrylonitrile), and poly(glycol), and blends and combinations thereof.

2. The hydrogel of claim 1 wherein the at least one perfluorocyclobutane crosslinking segment comprises a divalent moiety represented by formula —

X₁-L₁-(cycloC₄F₆)-L₂-X₂—

where L₁ and L₂ are the same or different and are a disubstituted aromatic group or disubstituted aromatic ether group; and

where X₁ and X₂ are the same or different and are ether, amino, silyl, ester, amide, sulfate or phosphate groups covalently attached to L₁ or L₂ and to the hydrophilic polymer.

3. The hydrogel of claim 2 wherein the at least one perfluorocyclobutane crosslinking segment is represented by the formula —

X₁—

C₆H₄—

O—

(cyclo-C₄F₆)—

O—

C₆H₄—

X₂—

.

4. The hydrogel of claim 2 wherein the at least one perfluorocyclobutane crosslinking segment is represented by the formula —

X₁—

C₆H₄-(cyclo-C₄F₆)—

O—

C₆H₄—

X₂—

.

5. The hydrogel of claim 2 wherein the at least one perfluorocyclobutane crosslinking segment is represented by the formula —

X₁—

C₆H₄-(cyclo-C₄F₆)—

C₆H₄—

X₂—

.

6. The hydrogel of claim 1 wherein the hydrophilic polymer chains have a molecular weight greater than about 50 kDa.

7. The hydrogel of claim 1 wherein the hydrophilic polymer chains are poly(vinyl alcohol).

8. The hydrogel of claim 1 wherein the hydrophilic polymer chains include a blend of more than one polymer.

9. A method of making a perfluorocyclobutane crosslinked hydrogel comprising:

attaching one or more substituted aromatic trifluorovinyl moieties to a hydrophilic polymer to form a modified polymer; and

heating the modified polymer to form perfluorocyclobutane segments from the substituted aromatic trifluorovinyl moieties for crosslinking the hydrophilic polymer, wherein the hydrophilic polymer is selected from the group consisting of poly(vinyl alcohol), poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(ethyleneimine), ethoxylated poly(ethyleneimine), poly(allylamine), poly(acrylamide), poly(acrylic acid), hydrolyzed poly(acrylonitrile), and poly(glycol), and blends and combinations thereof.

10. The method of claim 9 wherein the heating is at a temperature that does not degrade the hydrophilic polymer.

11. The method of claim 9 wherein the heating is at a temperature in the range from about room temperature to 240°

C.

12. The method of claim 9 wherein the attaching covalently links the substituted aromatic trifluorovinyl moieties to the hydrophilic polymer through an ether, amino, silyl, ester, amide, sulfate or phosphate group.

13. The method of claim 9 wherein the substituted aromatic trifluorovinyl moieties are trifluorovinyl ether groups and the hydrophilic polymer is poly(vinyl alcohol).

14. A method of making a perfluorocyclobutane crosslinked hydrogel article comprising:

attaching one or more substituted aromatic trifluorovinyl moieties to a hydrophilic polymer to form a modified polymer;

forming the modified polymer into an article precursor of predetermined shape; and

heating the article precursor to form a perfluorocyclobutane crosslinked hydrogel precursor having at least one perfluorocyclobutane crosslinking segment crosslinking the hydrophilic polymer wherein the hydrophilic polymer is selected from the group consisting of poly(vinyl alcohol), poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(ethyleneimine), ethoxylated poly(ethyleneimine), poly(allylamine), poly(acrylamide), poly(acrylic acid), hydrolyzed poly(acrylonitrile), and poly(glycol), and blends and combinations thereof.

15. The method of claim 14 further comprising hydrating the perfluorcyclobutane crosslinked hydrogel precursor.

16. A water-swellable article comprising a hydrophilic polymer crosslinked with at least one perfluorocyclobutane crosslinking segment wherein the hydrophilic polymer is selected from the group consisting of poly(vinyl alcohol), poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(ethyleneimine), ethoxylated poly(ethyleneimine), poly(allylamine), poly(acrylamide), poly(acrylic acid), hydrolyzed poly(acrylonitrile), and poly(glycol), and blends and combinations thereof.

17. The water-swellable article of claim 16 in the shape of a cylinder, teardrop, oval, or semi-lunar.

18. The water-swellable article of claim 16 used as a joint repair material.

19. The water-swellable article of claim 16 used as an articulating or bearing surface in a hip, knee, spine, finger, ankle, wrist, elbow or shoulder joint.