Blend hydrogels and methods of making

• US 20060188487A1
• Filed: 02/21/2006
• Published: 08/24/2006
• Est. Priority Date: 02/23/2005
• Status: Active Grant

• Current Assignee: Zimmer Incorporated (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Zimmer Technology Incorporated (Zimmer Biomet Holdings, Inc.)
• Inventors: Thomas, Brian, Yakimicki, Donald, Hudgins, Robert Garryl
• Granted Patent: US 8,017,139 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: C08J 2325/08 Copolymers of styrene C08J2329/08, C08J2335/06, C08J2355/02 take precedence
• CPC Class Codes: C08J 2329/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08J 2367/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds; C08J2367/06 takes precedence
• CPC Class Codes: C08J 3/005 Processes for mixing polymers
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08J 3/097 Sulfur containing compounds
• CPC Class Codes: C08J 3/11 from solid polymers
• CPC Class Codes: C08K 5/0016 Plasticisers
• CPC Class Codes: C08L 101/14 the macromolecular compounds being water soluble or water swellable, e.g. aqueous gels
• CPC Class Codes: C08L 23/26 modified by chemical after-treatment
• CPC Class Codes: C08L 25/08 Copolymers of styrene C08L29/08, C08L35/06, C08L55/02 take precedence
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 2666/04 Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 2666/14 Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 67/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds C08L67/06 takes precedence

Abstract

The present invention provides blend water-swellable materials and hydrogels suitable for use in biomedical or other applications. The blend water swellable materials and hydrogels have at least one hydrophilic polymer and at least one other polymer or oligomer having both hydrophobic and hydrophilic recurring units where the blend phase separates and is opaque and immiscible in the presence of water. Methods of making these blend water-swellable materials and hydrogels are also described.

Claims

1. A water-swellable material comprising a non-adhesive blend of

a) at least one hydrophilic polymer;

and

b) at least one polymer or oligomer having hydrophobic and hydrophilic recurring units, wherein the blend phase separates and is immiscible in the presence of water.

2. The water-swellable material of claim 1, wherein the hydrophilic polymer comprises poly(vinyl alcohol), poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(ethyleneimine), ethoxylated poly(ethyleneimine), poly(allylamine), poly(acrylamide), poly(acrylic acid), hydrolyzed poly(acrylonitrile), or poly(glycol).

3. The water-swellable material of claim 1, wherein the polymer or oligomer having hydrophobic and hydrophilic recurring units comprises a copolymer of ethylene and vinyl alcohol, a copolymer of styrene and allyl alcohol, or diol-terminated poly(hexamethylene phthalate).

4. The water-swellable material of claim 1, wherein the blend comprises about 5%-95% by weight of poly(vinyl alcohol) and about 5%-95% by weight of the polymer or oligomer having hydrophobic and hydrophilic recurring units.

5. The water-swellable material of claim 1, wherein a majority of the hydrophilic recurring units comprise pendant hydroxy groups.

6. The water-swellable material of claim 1, wherein the polymer or oligomer is a copolymer having hydrophobic recurring units of the form —

[CH₂CH₂—

] and hydrophilic recurring units of the form —

[CH₂CH(OH)].

7. The water-swellable material of claim 1, wherein the addition of a plasticizer enables the material to be processed as a thermoplastic.

8. The water swellable material of claim 7, wherein the plasticizer further comprises glycerine, ethylene glycol, propylene glycol, ethanol, tetrahydrofuran, toluene, poly(ethylene glycol), dimethylforamide, dimethylacetamide, acetone, acetonitrile, cyclohexane, cyclopentane, 1,4-dioxane, ethyl acetate, glyme, methyl-tert-butyl ether, methyl ethyl ketone, pyridine, dimethylsulfoxide, or water.

9. The water-swellable material of claim 7, wherein the material is a thermoplastic having a melting temperature in the range from about 70°

-200°

C.

26. The water-swellable material of claim 1 wherein the blend is crosslinked.

10. A hydrogel in hydrated form comprising a non-adhesive, phase separated blend of polymers comprising poly(vinyl alcohol) and a polymer having hydrophobic and hydrophilic recurring units.

11. The hydrogel of claim 10, wherein the hydrogel has a percent hydration in the range from about 10%-90%.

12. The hydrogel of claim 10, wherein the hydrogel has a percent strain at break of between 170-700.

13. The hydrogel of claim 10, wherein the hydrogel has a stress at peak value of greater than 200 psi.

14. A method for making a water-swellable material, comprising:

a) dissolving a blend of polymers comprising poly(vinyl alcohol) and a polymer having hydrophobic and hydrophilic recurring units in a suitable polar solvent including at least a minor fraction of water to produce a miscible blend; and

b) at least partially physically crosslinking the miscible blend to provide the water-swellable material.

15. The method of claim 14, wherein the solvent comprises dimethyl sulfoxide.

16. The method of claim 14, wherein the solvent comprises at least about 80% by weight dimethyl sulfoxide.

17. The method of claim 14, wherein the solvent consists essentially of dimethyl sulfoxide and water.

18. The method of claim 14, wherein the solution comprises about 0.5 parts by weight of the polymer blend per one part by weight solvent.

19. The method of claim 14, further comprising the step of contacting the blend of polymers with a second solvent to extract the polar solvent from the water-swellable material.

20. The method of claim 19, wherein the second solvent is ethanol.

21. The method of claim 14 wherein the crosslinking of the miscible blend is a freeze-thaw or solvent exchange process.

22. A method of using a thermoplastic water-swellable material to produce a hydrogel, the method comprising:

a) heating the thermoplastic material to a flow temperature to provide a flowable material;

b) cooling the flowable material to solidify the thermoplastic material; and

c) contacting the thermoplastic material with water or an aqueous solution to produce a hydrogel.

23. The method of claim 22, further comprising the step of shaping or molding the thermoplastic material.

24. The method of claim 22, wherein the method further comprises the step of extruding or injecting the thermoplastic material into a patient'"'"'s body.

25. The method of claim 22, wherein the aqueous solution comprises a biological fluid, an antibiotic, an analgesic, stem cells, antioxidant, hylauronic acid, salts, anti-inflammatory drugs, or a growth factor.