Hydrogels and methods for their production

• US 20050008705A1
• Filed: 06/30/2004
• Published: 01/13/2005
• Est. Priority Date: 04/10/2000
• Status: Active Grant

• Current Assignee: Amo Groningen B.V (Johnson & Johnson)
• Original Assignee: Amo Groningen B.V (Johnson & Johnson)
• Inventors: Pennings, Albert Johan, Spaans, Coenraad Jan, deGroot, Jacqueline Hermina
• Granted Patent: US 7,297,726 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: C08F 261/00 Macromolecular compounds obtained by polymerising monomers on to polymers of oxygen-containing monomers as defined in group C08F16/00
• CPC Class Codes: C08F 261/04 on to polymers of vinyl alcohol
• CPC Class Codes: C08F 283/00 Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
• CPC Class Codes: C08F 283/006 on to polymers provided for in C08G18/00 C08F283/004 takes precedence
• CPC Class Codes: C08L 29/00 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 alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers
• 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 29/06 Copolymers of allyl alcohol

Abstract

The present invention relates to new hydrogels with improved mechanical properties and methods of their preparation. The hydrogels are formed from hydrophilic polymers having function hydroxyl groups and have low elasticity modulus typically less than about 10 kPa, a tensile strength above 1 Mpa, an elongation above 50% which makes suitable as medical implants, in particular intraocular lenses. The hydrogels are prepared by a crosslinking method with a comparatively low concentration of hydrophilic polymer of a sufficiently high molecular weight dissolved in a good solvent.

Claims

1. A hydrogel comprising a network of hydrophilic polymers having hydroxyl group carrying carbon to carbon backbones having a tensile strength of at least 1 MPa.

2. A hydrogel according to claim 1 having an elasticity modulus less than about 10 kPa, preferably less than about 5 kPa.

3. A hydrogel according to claim 1 having a tensile strength of at least about 5 MPa.

4. A hydrogel according to claim 1 having an elongation of at least 50% at equilibrium water content.

5. A hydrogel according to claim 1 having sufficient optical clarity so as to obtain an optical transmission of at least about 40%.

6. A hydrogel according to claim 1 having a refractive index of at least about 1.40.

7. A hydrogel according to claim 1, wherein the hydrophilic polymers have a molecular weight of at least 200 000, preferably at least 300 000.

8. A hydrogel according to claim 1 having a polymer content between about 30 to 80% (wt), preferably between about 40 to 70% (wt).

9. A hydrogel according to claim 1, wherein the hydrophilic polymer is chemically modified with agent capable of reducing its equilibrium water content.

10. A hydrogel according to claim 9, wherein said agent is a monoisocyanate.

11. A hydrogel according to claim 10, wherein said monoisocyanate is a lower alkyl, aryl or arylalkyl isocyanate.

12. A hydrogel according to claim 1 wherein the hydrophilic polymer is selected from at least one of the polymers —

(CH₂—

CHOH)_n—

(polyvinyl alcohol);

—

(CH₂—

CH₂)_n(CH₂—

CHOH)_m—

(copolymer of ethylene and vinyl alcohol);

—

(CH₂—

CH₂—

CHOH)_n—

(poly(1-hydroxy-1,3-propanediyl) and —

(CH₂—

CH(CH₂OH))_n—

(polyallyl alcohol).

13. A hydrogel according to claim 12, wherein the hydrophilic polymer is polyallyl alcohol.

14. A hydrogel according to claim 1, wherein the network is formed by crosslinks between the hydrophilic polymers.

15. A hydrogel according to claim 14, wherein the crosslinking density is less than about 10%, preferably less than about 5%.

16. A hydrogel according to claim 15 crosslinked by means of a diisocyanate.

17. A hydrogel according to claim 16, wherein said diisocyanate has a formula OCN—

(CH₂)₄—

NH—

C(O)O—

(CH₂)₄—

O(O)C—

NH—

(CH₂)₄—

NCO.

18. A hydrogel according to claim 16 having crosslinks of the formula —

O—

C(O)—

NH—

R—

NH—

C(O)—

O—

, wherein R is a spacing group.

19. A hydrogel according to claim 9, wherein R is an optionally substituted lower alkyl group having between one and ten carbon atoms.

20. A hydrogel according to claim 19, wherein R is —

(CH₂)₄—

21. A hydrogel according to claim 14 crosslinked by means of an epoxy compound.

22. A hydrogel according to claim 12, wherein the hydrophilic polymer poly(1-hydroxy-1,3-propanediyl.

23. A hydrogel according to claim 22 crosslinked with diisocyanates.

27. An implant made of a hydrogel according to any of claims 1 to 26

28. An ophthalmic lens made of a hydrogel according to any of claims 1 to 24.

29. An ophthalmic lens according to claim 27 having

(a) an elasticity modulus less than about 10 kPa, preferably less than about 5 kPa;

(b) a tensile strength of at least about 1 MPa;

(c) an elongation of at least 50% at equilibrium water content;

(d) sufficient optical clarity so as to obtain an optical transmission of at least about 40%; and

(e) a refractive index of at least about 1.40.

24. A hydrogel comprising poly(1-hydroxy-1,3-propanediyl) crosslinked with a lower alkyl diisocyanate.

25. A hydrogel according to claim 24, wherein said lower alkyl diisocyanate is 1,4-butanediisocyanate.

26. A hydrogel according to claim 24, wherein the hydroxyl groups of poly(1-hydroxy-1,3-propanediyl is modified with a monoiscyanate before being crosslinked with a lower alkyl diisocyanate.

30. A method of preparing a hydrogel having a low elasticity modulus from a hydrophilic polymer comprising the steps of:

(a) selecting hydrophilic polymer of sufficiently high molecular weight;

(b) dissolving said polymer in a good solvent to a concentration not exceeding about 5% (wt);

(c) adding a crosslinking agent;

(d) mixing and reacting polymer with crosslinker;

(e) evaporating said solvent;

(f) optionally adding water.

31. A method according to claim 30, wherein the crosslinking agent is a diisocyanate.

32. A method according to claim 30, wherein the hydrophilic polymer has a molecular weight of at least about 200 000, preferably at least about 300 000.

33. A method according to claim 30 further comprising degassing the solution of polymer in good solvent.

34. A method according to claim 30 further comprising the step of chemically modifying the polymer so as to reduce its hydrophilicity.

35. A method according to claim 30, wherein the hydrophilic polymers have hydroxyl group carrying carbon-carbon backbone

36. A method according to claim 35, wherein the hydrophilic polymers are selected from at least one of the polymers —

(CH₂—

CHOH)_n—

(polyvinyl alcohol);

—

(CH₂—

CH₂)_n(CH₂—

CHOH)_m—

(copolymer of ethylene and vinyl alcohol);

—

(CH₂—

CH₂—

CHOH)_n—

(poly(1-hydroxy-1,3-propanediyl)) and —

(CH₂—

CH(CH₂OH))_n—

(polyallyl alcohol).

37. A method according to claim 35 characterized by modifying the hydrophilic polymer by reacting it with a mono-isocyanate.

38. A method according to claim 37 characterized by modifying less than 15%, preferably less than 10% of their hydroxyl groups.

39. A method according to claim 30 characterized by performing the crosslinking at constant volume.

40. A method according to claim 30 resulting in the formation of a hydrogel having an elasticity modulus less than about 10 kPa, preferably less than about 5 kPa.

41. A method according to claim 36 wherein the hydrophilic polymer is (poly(1-hydroxy-1,3-propanediyl).

42. A method according to claim 41 wherein the crosslinker is a diisocyanate.