Polymerizable chain-extended polysiloxanes with pendant hydrophilic groups

• US 9,109,091 B2
• Filed: 02/10/2015
• Issued: 08/18/2015
• Est. Priority Date: 10/06/2010
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Chang, Frank, Huang, Jinyu, Sanders, Laura Ann
• Primary Examiner(s): Schnizer, Richard
• Assistant Examiner(s): Pipic, Alma
• Application Number:
  US14/618,135
• Publication Number:
  US 20150152228A1
• Time in Patent Office: 189 Days
• Field of Search: 523/107, 525/479, 424/429
• US Class Current: 1/1
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C08F 290/068 Polysiloxanes
• CPC Class Codes: C08G 77/20 containing silicon bound to unsaturated aliphatic groups C08G77/045 takes precedence
• CPC Class Codes: C08G 77/28 sulfur-containing groups
• CPC Class Codes: C08G 77/46 containing polyether sequences
• CPC Class Codes: C08G 77/48 in which at least two but not all the silicon atoms are connected by linkages other than oxygen atoms C08G77/42 takes precedence
• CPC Class Codes: C08L 83/12 containing polyether sequences
• CPC Class Codes: C08L 83/14 in which at least two but not all the silicon atoms are connected by linkages other than oxygen atoms C08L83/10 takes precedence
• CPC Class Codes: G02B 1/043 Contact lenses

Abstract

The invention provide a class of chain-extended polysiloxane crosslinkers which comprises (1) at least two polylsiloxane segments, wherein each pair of adjacent polysiloxane segments is linked by one divalent organic radical which includes at least one pendant hydrophilic group (hydroxyl and/or carboxyl groups) or at least one dangling hydrophilic polymer chain and a di-thioether linkage —S-DR-S— in which DR is a divalent organic radical; and (2) two terminal ethylenically unsaturated groups. The present invention is also related to a polymer comprising crosslinking units derived from chain-extended polysiloxane crosslinker of the invention and to ophthalmic lenses comprising such a polymer.

Claims

1. A soluble amphiphilic prepolymer, comprising two terminal ethylenically-unsaturated groups and at least two polysiloxane segments separated by an organic linkage having one or more dangling hydrophilic polymer chains, wherein the prepolymer is obtained by reacting a hydrophilic polymer having one sole terminal reactive functional group with a chain-extended polysiloxane crosslinker of formula (I), in the presence or absence of a coupling agent, to form the amphiphilic prepolymer having the dangling hydrophophilic chains,

2. The prepolymer of claim 1, wherein the hydrophilic polymer is selected from the group consisting of monofunctional group-terminated poly(ethylene glycol) (PEG), monofunctional group-terminated PEG/PPG block copolymers, monofunctional group-terminated polyalkylacrylamides, monofunctional group-terminated polyalkylmethacrylamides, monofunctional group-terminated polyvinylpyrrolidones, monofunctional group-terminated copolymers of N-vinylpyrrolidone with one or more vinylic monomers free of any reactive functional group, monofunctional group-terminated polymer of one or more hydrophilic vinylic monomers free of reactive functional group other than ethylenically unsaturated group, and combinations thereof.

3. The soluble amphiphilic prepolymer of claim 1, wherein BG is (i) a linear C₃-C₇alkylene divalent radical having at least one hydroxyl or carboxyl group, a branched C₃-C₇alkylene divalent radical having at least one hydroxyl or carboxyl group, (ii) a divalent radical of —

[CH₂CH(T)CH₂O]_r4—

[CH(R″

)CH₂O]_r3—

[CH₂CH(T)CH₂]_r5—

in which R″

is H or methyl, r3 is an integer of 1 to 20, T is hydroxyl or carboxyl group, and r4 and r5 independent of each other are 0 or 1, or (iii) combinations thereof.

4. A polymer, comprising:

(1) crosslinking units derived from at least one chain-extended polysiloxane crosslinker of claim 1;

(2) hydrophilic units derived from at least one hydrophilic vinylic monomer;

(3) optionally hydrophobic units derived from a hydrophobic vinylic monomer; and

(4) optionally UV-absorbing units derived from a polymerizable UV-absorbing agent.

5. The polymer of claim 4, which is a soluble prepolymer obtained by first polymerizing a polymerizable composition including (a) a chain-extended polysiloxane crosslinker of claim 1 or an amphiphilic prepolymer having dangling hydrophilic polymer chains of claim 1, (b) at least one hydrophilic vinylic monomer, (c) a chain transfer agent with or without a first reactive functional group, other than a thiol group, and/or a vinylic monomer having a second reactive functional group other than an ethylenically unsaturated group, (d) optionally a hydrophobic vinylic monomer, and (e) optionally a polymerizable UV-absorbing agent, to form an intermediary copolymer and then by ethylenically functionalizing the intermediary copolymer with an ethylenically functionalizing vinylic monomer having a third reactive functional group capable of reacting with the first or second reactive functional group to form a linkage in a coupling reaction in the presence or absence of a coupling agent to form the prepolymer, wherein the first, second and third reactive functional groups independent of one another are selected from the group consisting of amino group —

NHR′

with R′

as defined above, hydroxyl group, carboxyl group, acid halide group, azlactone group, isocyanate group, epoxy group, aziridine group, and a combination thereof.

6. An ophthalmic lens, comprising a silicone hydrogel material that is obtained by curing a lens-forming composition including a chain-extended polysiloxane crosslinker of claim 1 in a mold, wherein the lens-forming composition further comprises one or more components selected from the group consisting of a hydrophilic vinylic monomer, a hydrophobic vinylic monomer, a polysiloxane-containing vinylic monomer, a polysiloxane-containing vinylic macromer, a crosslinking agent having a molecular weight of less than 700 Daltons, a polymerizable UV-absorbing agent, a visibility tinting agent, an antimicrobial agent, a bioactive agent, a leachable lubricant, a leachable tear-stabilizing agent, and mixtures thereof, wherein the ophthalmic lens has at least one property selected from the group consisting of:

an oxygen permeability of at least about 40 barrers;

an elastic modulus of from about 0.1 MPa to about 2.0 MPa;

an Ionoflux Diffusion Coefficient, D, of at least about 1.0×

10<sup>−

5</sup> mm²/min;

a water content of from about 15% to about 55% by weight when fully hydrated; and

combinations thereof.

7. The prepolymer of claim 1, wherein the chain-extended polysiloxane crosslinker is obtained by reacting at least one polysiloxane crosslinker of formula (2) with at least one dimercaptan, under Michael Addition or thiol-ene reaction conditions,

8. The prepolymer of claim 7, wherein said at least one polysiloxane crosslinker comprises at least one hydroxyl group and is obtained by ethylenically-functionalizing of:

(1) a di-epoxy terminated polysiloxane with use of an ethylenically-functionalizing vinylic monomer selected from the group consisting of C₂ to C₆ hydroxylalkyl (meth)acrylate, C₂ to C₆ hydroxyalkyl (meth)acrylamide, allyl alcohol, allylamine, amino-C₂-C₆ alkyl (meth)acrylate, C₁-C₆ alkylamino-C₂-C₆ alkyl (meth)acrylate, vinylamine, amino-C₂-C₆ alkyl (meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl (meth)acrylamide, acrylic acid, C₁-C₄ alkylacrylic acid, N-[tris(hydroxymethyl)-methyl]acrylamide, N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic acid), alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, and combination thereof;

(2) a polysiloxane having two terminal function groups selected from the group consisting of hydroxyl groups, amino groups, carboxyl groups, and combination thereof with use of an epoxy-containing vinylic monomer;

(3) a polysiloxane having two terminal function groups selected from the group consisting of hydroxyl groups, amino groups, carboxyl groups, and combinations thereof with use of an ethylenically-functionalizing vinylic monomer selected from the group consisting of C₂ to C₆ hydroxylalkyl (meth)acrylate, C₂ to C₆ hydroxyalkyl (meth)acrylamide, allylalcohol, allylamine, amino-C₂-C₆ alkyl (meth)acrylate, C₁-C₆ alkylamino-C₂-C₆ alkyl (meth)acrylate, vinylamine, amino-C₂-C₆ alkyl (meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl (meth)acrylamide, acrylic acid, C₁-C₄ alkylacrylic acid, N-[tris(hydroxymethyl)-methyl]acrylamide, N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic acid), alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl-1,3-butadiene, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, and a combination thereof in the presence of a di-epoxy compound;

(4) a di-epoxy-terminated polysiloxane with use of glycidyl(meth)acrylate in the presence of a diol, di-amine compound, di-carboxylic acid compound, or a combination thereof;

or (5) combinations thereof.

9. The prepolymer of claim 7, wherein said at least one polysiloxane crosslinker is:

α

,ω

-bis[3-(meth)acryloxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acryloxyethoxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acryloxyethylamino-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acrylamidoethoxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[(meth)acrylamidoethylamino-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acryloxypropoxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acrylamidopropoxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acrylamidopropylamino-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[3-(meth)acrylamidoisopropoxy-2-hydroxypropyloxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis(allyloxy-2-hydroxypropyl-oxyethoxypropyl)-terminated polydimethylsiloxane, α

,ω

-bis(allylamino-2-hydroxypropyloxypropyl)-terminated polydimethylsiloxane, α

,ω

-bis(vinylamino-2-hydroxypropyloxypropyl)-terminated polydimethylsiloxane, α

,ω

-bis(allyloxy-2-hydroxypropyl-oxypropyl)-terminated polydimethylsiloxane, α

,ω

-bis(vinyloxy-2-hydroxypropyl-oxyethoxypropyl)-terminated polydimethylsiloxane, α

,ω

-bis[(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl]-terminated polydimethylsiloxane, α

,ω

-bis[(meth)acryloxy-2-hydroxypropyl-N-ethylaminopropyl]-terminated polydimethylsiloxane, α

,ω

-bis[(meth)acryloxy-2-hydroxypropyl-aminopropyl]-polydimethylsiloxane, α

,ω

-bis[allyloxy-2-hydroxypropyl-N-ethylaminopropyl]-terminated polydimethylsiloxane, α

,ω

-bis[vinyloxy-2-hydroxypropyl-N-ethylaminopropyl]-terminated polydimethylsiloxane, α

,ω

-bis[(meth)acryloxy-2-hydroxypropyl-oxycarbonylpropyl]-terminated polydimethylsiloxane, α

,ω

-bis[allyloxy-2-hydroxypropyl-oxycarbonylpropyl]-terminated polydimethylsiloxane, α

,ω

-bis[vinyloxy-2-hydroxypropyl-oxycarbonylpropyl]-terminated polydimethylsiloxane, α

,ω

-bis[(meth)acryloxy-2-hydroxypropyl-oxy-penylcarbonyloxyalkyl]-terminated polydimethylsiloxane, α

,ω

-bis[allyloxy-2-hydroxypropyl-oxy-pentylcarbonyloxyalkyl]-terminated polydimethylsiloxane, α

,ω

-bis[vinyloxy-2-hydroxypropyl-oxy-pentylcarbonyloxyalkyl]-terminated polydimethylsiloxane, α

,ω

-bis(allyloxy-2-hydroxypropyl-oxy(polyethylenoxy)propyl)-terminated polydimethylsiloxane, α

,ω

-bis(vinyloxy-2-hydroxypropyl-oxy(polyethylenoxy)propyl)-terminated polydimethylsiloxane, α

,ω

-bis[(meth)acryloxy-2-hydroxypropyl-oxy(polyethylenoxy)propyl]-terminated polydimethylsiloxane, a coupling product of C₂-C₄ hydroxyalkyl(meth)acrylate or C₂-C₄ hydroxyalkyl(meth)acrylamide or (meth)acrylic acid with α

,ω

-bis(hydroxyethoxypropyl)-polydimethylsiloxane through a di-epoxy compound, and combinations thereof.

10. The prepolymer of claim 9, wherein said at least one dimercaptan is selected from the group consisting of C₂-C₁₂ alkyl dimercaptans, ethylcyclohexyl dimercaptan, dipentene dimercaptan, benzenedithiol, methyl-substituted benzenedithiol, benzenedimethanethiol, glycol dimercaptoacetate, ethyl ether dimercaptan, triglycol dimercaptan, tetraglycol dimercaptan, and combinations thereof.

11. The prepolymer of claim 9, wherein said at least one dimercaptan comprises at least one hydroxy and/or carboxyl group.

12. The prepolymer of claim 7, wherein said at least one polysiloxane crosslinker is free of any hydroxy or carboxyl group, and wherein said at least one dimercaptan comprises at least one hydroxy and/or carboxyl group.

13. The prepolymer of claim 12, wherein said at least one dimercaptan is dimercaprol, dimercaptobutanol, dimercaptopentanol, dithiothreitol, dimercaptopropionic acid, dihydrolipoic acid, dimercaptosuccinic acid, or combinations thereof.

14. The prepolymer of claim 13, wherein said at least one dimercaptan is dimercaptopropionic acid, dihydrolipoic acid, dimercaptosuccinic acid, or combinations thereof.