Chain-extended polysiloxane crosslinkers with dangling hydrophilic polymer chains

• US 8,835,525 B2
• Filed: 10/05/2011
• Issued: 09/16/2014
• Est. Priority Date: 10/06/2010
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Kuyu, Selma, Smith, Dawn Alison, Huang, Jinyu, Chang, Frank, Scott, Robert, Medina, Arturo Norberto, Shankernarayanan, Manivakkam J.
• Primary Examiner(s): Schnizer, Richard
• Assistant Examiner(s): Pipic, Alma
• Application Number:
  US13/253,177
• Publication Number:
  US 20120088844A1
• Time in Patent Office: 1,077 Days
• Field of Search: 523/107, 525/479
• US Class Current: 523/107
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C08G 77/20 containing silicon bound to unsaturated aliphatic groups C08G77/045 takes precedence
• CPC Class Codes: C08G 77/38 Polysiloxanes modified by chemical after-treatment C08G77/045 takes precedence
• CPC Class Codes: C08G 77/42 Block-or graft-polymers containing polysiloxane sequences polymerising aliphatic unsaturated monomers on to a polysiloxane C08F283/12
• CPC Class Codes: C08G 77/442 containing vinyl polymer sequences
• CPC Class Codes: C08G 77/46 containing polyether sequences
• CPC Class Codes: C08L 83/10 Block- or graft-copolymers containing polysiloxane sequences obtained by polymerising a compound having a carbon-to-carbon double bond on to a polysiloxane C08L51/08, C08L53/00
• 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
• CPC Class Codes: G02B 2207/109 Sols, gels, sol-gel materials

Abstract

The invention provide a class of linear chain-extended polysiloxane crosslinkers which comprises two terminal ethylenically unsaturated groups, at least two polysiloxane segments, and dangling hydrophilic polymer chains each covalently attached to a divalent organic radical separating each pair of adjacent polysiloxane segments. 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 linear chain-extended polysiloxane crosslinker, comprising:

(1) two terminal ethylenically unsaturated groups;

(2) at least two polysiloxane segments; and

(3) at least one dangling hydrophilic polymer chain covalently attached to a divalent organic radical separating said at least two polysiloxane segments,

wherein the linear chain extended polysiloxane crosslinker is as set forth by formula (I)

2. The chain-extended polysiloxane crosslinker of claim 1, wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₁′

, R₂′

, R₃′

, R₄′

, R₅′

, R₆′

, R₇′

, and R₈′

are methyl.

3. The chain-extended polysiloxane crosslinker of claim 1, wherein t1, t2 and t3 in formula (I) are an integer of 1, wherein the chain-extended polysiloxane crosslinker is obtained by a process including the steps of:

(1) obtaining a bridging linker having a pendant, linear or 3-arm, hydrophilic polymer chain and two first reactive functional groups by

(a) reacting a mercaptan having one sole thiol group and two first reactive functional groups, other than thiol groups, with a mono-ethylenically-functionalized hydrophilic polymer, under Michael Addition or thiol-ene reaction conditions,

(b) reacting a mono-thiol terminated, linear or Y-shape, hydrophilic polymer with a vinylic monomer having two first reactive functional groups, other than thiol groups, under Michael Addition or thiol-ene reaction conditions, or

(c) polymerizing a mixture including a chain transfer agent having one sole thiol group and at least two first reactive functional groups, at least about 60% by weight of one or more hydrophilic vinylic monomers and from 0 to about 40% by weight of one or more vinylic monomers selected from the group consisting of N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)-silylpropyl](meth)acrylamide, N-[tris(dimethyl-phenylsiloxy)-silylpropyl](meth)acrylamide, N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)-2-methyl acrylamide, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methyl acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]acrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)-2-methyl acrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methyl acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide, N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl acrylamide, N-[2-hydroxy-3-(3-(t-butyldimethyl-silyl)propyloxy)propyl]acrylamide, N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy) propyl]-2-methyl acrylamide, N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide, 3-methacryloxy propylpentamethyldisiloxane, tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane), (3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane, 3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane, N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silyl carbamate, 3-(trimethylsilyl)propylvinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane, 3-[tris(trimethylsiloxy)silyl]propylvinyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, t-butyldimethyl-siloxyethyl vinyl carbonate, trimethylsilylethyl vinyl carbonate, trimethylsilylmethyl vinyl carbonate, t-butyl (meth)acrylate, cyclohexylacrylate, isobornyl methacrylate, a polysiloxane-containing vinylic monomer having 3 to 8 silicone atoms, and combinations thereof;

(2) reacting the bridging linker with at least one di-functional polysiloxane having one sole polysiloxane segment and two terminal second reactive functional groups, in the presence or absence of a coupling agent under coupling reaction conditions, to form an intermediary chain-extended polysiloxane polymer having two terminal first or second reactive functional groups, at least two polysiloxane segments, and at least one dangling hydrophilic polymer chain attached to an organic linkage linking a pair of adjacent polysiloxane segments; and

(3) ethylenically functionalizing the intermediary chain-extended polysiloxane polymer by using an ethylenically functionalizing vinylic monomer having a third reactive functional group, other than ethylenically unsaturated group, capable of reacting with the first or second reactive functional groups in the presence or absence of a coupling agent to form a covalent linkage, thereby forming the chain-extended polysiloxane crosslinker,

wherein, the first reactive functional group is selected from the group consisting of amino group of —

NHR′

with R′

as defined above, hydroxyl group, carboxyl group, and combinations thereof, and the second and third reactive functional groups independent of each other are selected from the group consisting of hydroxyl groups, amino groups, carboxyl groups, isocyanate groups, epoxy groups, aziridine group, azlactone group, acid chloride, and combinations thereof.

4. The chain-extended polysiloxane crosslinker of claim 3, wherein the mercaptan is selected from the group consisting of mercaptoglycerol, 2-mercapto-pyrimidine-4,6-diol, 4-amino-5-mercapto-pentanoic acid, 2-mercapto-4-amino-6-hydroxypyrimidine, 2-mercapto-succinic acid, 3-mercapto-2-(methylamino)propanoic acid, 2-mercapto-4,5-dihydro-1H-imidazole-4,5-diol, 3-mercaptotyramine, mercaptopropanediol, 2-mercaptomethylglutaric acid, 3-mercapto-DL-valine hydrochloride, and combinations thereof;

wherein the vinylic monomer having two first reactive functional groups is selected from the group consisting of N,N-2-(meth)acrylamidoglycolic acid, glycerol (meth)acrylate,

2-hydroxy-3-aminopropyl (meth)acrylate, 1-hydroxy-2-aminopropyl (meth)acrylate, 1-amino-2-hydroxypropyl (meth)acrylate, glutaconic acid, itaconic acid, citraconic acid, mesaconic acid, maleic acid, fumaric acid, and combinations thereof wherein said at least one di-functional polysiloxane is selected from the group consisting of a di-epoxypropoxypropyl-terminated polysiloxane, a di-hydroxyethoxypropyl-terminated polysiloxane, a di-hydroxyl(polyethylenoxy)propyl-terminated polysiloxane, dicarboxydecyl-terminated polysiloxane, a dicarboxypropyl-terminated polysiloxane, a di-caprolactone terminated polysiloxane, a di-N-ethylaminopropyl terminated polysiloxane, di-aminopropyl terminated polysiloxane, a di-succinic acid anhydride terminated polysiloxane, and combinations thereof.

5. The chain-extended polysiloxane crosslinker of claim 1, wherein in formula (I) t1, t2 and t3 are zero, wherein the chain-extended polysiloxane crosslinker is obtained by a process including the steps of:

(1) obtaining a bridging linker having a pendant linear or 3-arm hydrophilic polymer chain and two first reactive functional groups selected from the group consisting of amino, hydroxyl, carboxyl, isocyanate groups, and combinations thereof by

(a) reacting a C₂-C₂₀ compound having three first reactive functional groups with a linear or 3-arm hydrophilic polymer having one sole terminal second reactive functional group in the presence or absence of a coupling agent under coupling reaction conditions, or

(b) reacting a C₂-C₂₀ compound having three first functional groups reactive with an organic bromide with an atom transfer radical polymerization (ATRP) product obtained from a mixture including an organic bromide as ATRP initiator, at least about 60% by weight of one or more hydrophilic vinylic monomers and from 0 to about 40% by weight of one or more vinylic monomers selected from the group consisting of N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide, N-[tris(dimethylpropylsiloxy)-silylpropyl](meth)acrylamide, N-[tris(dimethyl-phenylsiloxy)-silylpropyl](meth)acrylamide, N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)-2-methyl acrylamide, N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methyl acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]acrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)-2-methyl acrylamide, N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methyl acrylamide, N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide, N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl acrylamide, N-[2-hydroxy-3-(3-(t-butyldimethyl-silyl)propyloxy)propyl]acrylamide, N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy) propyl]-2-methyl acrylamide, N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide, 3-methacryloxy propylpentamethyldisiloxane, tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane), (3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane, 3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane, N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silyl carbamate, 3-(trimethylsilyl)propylvinyl carbonate, 3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane, 3-[tris(trimethylsiloxy)silyl]propylvinyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, t-butyldimethyl-siloxyethyl vinyl carbonate, trimethylsilylethyl vinyl carbonate, trimethylsilylmethyl vinyl carbonate, t-butyl (meth)acrylate, cyclohexylacrylate, isobornyl methacrylate, a polysiloxane-containing vinylic monomer having 3 to 8 silicone atoms, and combinations thereof;

(2) reacting the bridging linker with at least one di-functional polysiloxane having one sole polysiloxane segment and two terminal third reactive functional groups, in the presence or absence of a coupling agent under coupling reaction conditions, to form an intermediary chain-extended polysiloxane polymer having two terminal first or third reactive functional groups, at least two polysiloxane segments, and at least one dangling hydrophilic polymer chain attached to an organic linkage linking a pair of adjacent polysiloxane segments; and

(3) ethylenically functionalizing the intermediary chain-extended polysiloxane polymer by using an ethylenically functionalizing vinylic monomer having a fourth reactive functional group other than ethylenically unsaturated group capable of reacting with the first or third reactive functional groups in the presence or absence of a coupling agent to form a covalent linkage, thereby forming the chain-extended polysiloxane crosslinker, wherein the second, third and fourth reactive functional groups independent of one another are selected from the group consisting of hydroxyl groups, amino groups, carboxyl groups, epoxy groups, isocyanate groups, azlactone group, acid chloride, and combinations thereof.

6. The chain-extended polysiloxane crosslinker of claim 3, wherein the ethylenically-functionalizing vinylic monomer is 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, alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, 2-(1-aziridinyl)ethyl (meth)acrylate, 3-(1-aziridinyl) propyl (meth)acrylate, 4-(1-aziridinyl) butyl (meth)acrylate, 6-(1-aziridinyl) hexyl (meth)acrylate, 8-(1-aziridinyl) octyl (meth)acrylate), glycidyl (meth)acrylate, vinyl glycidyl ether, allyl glycidyl ether, (meth)acrylic acid halide groups, C₁ to C₆ isocyanatoalkyl (meth)acrylate, 2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-vinyl-4-methyl-4-ethyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one, 2-vinyl-4,4-dibutyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one, 2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one, 2-vinyl-4,4-diethyl-1,3-oxazolin-5-one, 2-vinyl-4-methyl-4-nonyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-phenyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one, 2-vinyl-4,4-pentamethylene-1,3-oxazolin-5-one, 2-vinyl-4,4-dimethyl-1,3-oxazolin-6-one, and combinations thereof.

7. The chain-extended polysiloxane crosslinker of claim 5, wherein the ethylenically-functionalizing vinylic monomer is 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, alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxyl-4-phenyl butadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, 2-(1-aziridinyl)ethyl (meth)acrylate, 3-(1-aziridinyl) propyl (meth)acrylate, 4-(1-aziridinyl) butyl (meth)acrylate, 6-(1-aziridinyl) hexyl (meth)acrylate, 8-(1-aziridinyl)octyl (meth)acylate, glycidyl (meth)acrylate, vinyl glycidyl ether, allyl glycidyl ether, (meth)acrylic acid halide groups, C₁ to C₆ isocyanatoalkyl (meth)acrylate, 2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-vinyl-4-methyl-4-ethyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one, 2-vinyl-4,4-dibutyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one, 2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one, 2-vinyl-4,4-diethyl-1,3-oxazolin-5-one, 2-vinyl-4-methyl-4-nonyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-phenyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one, 2-vinyl-4,4-pentamethylene-1,3-oxazolin-5-one, 2-vinyl-4,4-dimethyl-1,3-oxazolin-6-one, and combinations thereof.

8. The chain-extended polysiloxane crosslinker of claim 1, wherein is a linear or 3-arm hydrophilic polymer chain that comprises at least about 80% by weight of one or more hydrophilic monomeric units selected from the group consisting of ethyleneoxide units, (meth)acrylamide units, C₁-C₃ alkyl (meth)acrylamide units, di-(C₁-C₃ alkyl) (meth)acrylamide units, N-vinylpyrrole units, N-vinyl-2-pyrrolidone units, 2-vinyloxazoline units, 4-vinylpyridine units, mono-C₁-C₄ alkoxy, mono-(meth)acryloyl terminated polyethyleneglycol units having a molecular weight of 600 Daltons or less, di(C₁-C₃ alkyl amino)(C₂-C₄ alkyl) (meth)acrylate units, N—

C_1-C₄ alkyl-3-methylene-2-pyrrolidone units, N—

C₁-C₄ alkyl-5-methylene-2-pyrrolidone units, N-vinyl C₁-C₆ alkylamide units, N-vinyl-N—

C₁-C₆ alkyl amide units, and combinations thereof.

9. The chain-extended polysiloxane crosslinker of claim 8, wherein is a linear hydrophilic polymer chain.

10. The chain-extended polysiloxane crosslinker of claim 8, wherein is a 3-arm hydrophilic polymer chain.