# US 10,371,865 B2 · Silicone hydrogels comprising polyamides

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- Number: US 10,371,865 B2
- Document ID: US10371865B2
- Status: Granted
- Kind: B2
- Application number: 15/609,074
- Filed: 2017-05-31
- Published: 2018-01-11
- Granted: 2019-08-06
- Earliest claimed: 2016-07-06
- Assignees: Johnson & Johnson Vision Care, Inc.
- Applicants: Johnson & Johnson Vision Care, Inc.
- Inventors: Azaam Alli; Alexander Guzman
- Web page: https://patentgrep.com/patent/US10371865B2

## CPC

- G02B 1/043: {Contact lenses}
- C08F 271/00: Macromolecular compounds obtained by polymerising monomers on to polymers of nitrogen-containing monomers as defined in group C08F26/00
- C08F 271/02: on to polymers of monomers containing heterocyclic nitrogen
- C08F 290/068: {Polysiloxanes}
- C08G 77/442: containing vinyl polymer sequences
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS

## Abstract

Described are silicone hydrogels that are more biocompatible than current ocular materials. The silicone hydrogels are formed from a reactive monomer mixture comprising: a mixture of hydroxyl substituted silicone containing components, at least one polyamide; and at least one hydrophilic monomer. The silicone hydrogels also display a desirable balance of properties, including clarity, oxygen permeability, wettability and desirable protein uptake.

## Claims

### Claim 1

A silicone hydrogel formed from a reactive monomer mixture comprising:
a) between about 1 and about 15 wt % at least one polyamide;
b) at least one first mono-functional, hydroxyl substituted poly(disubstituted siloxane) having 4 to 8 siloxane repeating units;
c) at least one second hydroxyl substituted poly(disubstituted siloxane) that is a mono-functional hydroxyl substituted poly(disubstituted siloxane)s having 10 to 200 siloxane repeating units;
d) about 5 to about 35 wt % of at least one hydrophilic monomer;
wherein the first hydroxyl substituted poly(disubstituted siloxane) and the second mono-functional hydroxyl substituted poly(disubstituted siloxane) are present in concentrations to provide a ratio of wt % of all first hydroxyl substituted poly(disubstituted siloxane) to wt % of all second hydroxyl substituted poly(disubstituted siloxane)s of 0.4-1.3.

### Claim 2 (depends on 1)

The silicone hydrogel of claim 1, wherein the first monofunctional hydroxyl substituted, poly(disubstituted siloxane) comprises compounds of Formula VII-1
wherein
Z is selected from O, N, S or NCH2CH2O, wherein when Z is O or S then R2 is not present;
R1 is independently H or methyl;
R2 is H or is a linear, branched, or cyclic alkyl group containing one to eight carbon atoms, any of which may be further substituted with at least one hydroxy group, amide, ether, and combinations thereof;
R3 and R4 are independently a linear, branched, or cyclic alkyl group containing one to eight carbon atoms, any of which may be further substituted with at least one hydroxy group, amide, ether, and combinations thereof;
n is 4-8; and
R5 is selected from straight or branched C1 to C8 alkyl groups, which may be optionally substituted with one or more hydroxyl, amide, ether, and combinations thereof.

### Claim 3 (depends on 1)

The silicone hydrogel of claim 1, wherein the second hydroxyl substituted, poly(disubstituted siloxane) comprises a compound of Formula VII-2:
wherein Z is selected from O, N, S or NCH2CH2O, when Z is O or S R2 is not present;
R1 is independently H or methyl;
R2 is H or is a linear, branched, or cyclic alkyl group containing one to eight carbon atoms, any of which may be further substituted with at least one hydroxy group, amide, ether, and combinations thereof;
R3 and R4 are independently a linear, branched, or cyclic alkyl group containing one to eight carbon atoms, any of which may be further substituted with at least one hydroxy group, and which may be optionally substituted with amide, ether, and combinations thereof;
n is the number of siloxane units and is from 10 to 200; and
R5 is selected from straight or branched C1 to C8 alkyl groups, which may be optionally substituted with one or more hydroxyl, amide, ether, and combinations thereof.

### Claim 4 (depends on 1)

The silicone hydrogel of claim 1, further comprising a di-functional hydroxyl-substituted poly(disubstituted siloxane) of Formula XI
wherein
wherein R1 is independently a hydrogen atom or methyl group;
R2 and R3 are independently a linear, branched, or cyclic alkyl group containing one to eight carbon atoms, any of which may be further substituted with at least one hydroxy group, amido, ether, amino, carboxyl, carbonyl groups and combinations thereof; or are selected from —(CH2CH2O)xOCH3 where x is from 1 to 20; and
n is from 1 to 200.

### Claim 5 (depends on 1)

The silicone hydrogel of claim 1, wherein the first mono-functional hydroxyl-substituted poly(disubstituted siloxane) and the second hydroxyl-substituted poly(disubstituted siloxane) are present in the reactive monomer mixture in a total concentration between about 40 and about 70 wt %.

### Claim 6 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide comprises a cyclic polyamide, an acyclic polyamide, or a mixture of a cyclic polyamide and an acyclic polyamide.

### Claim 7 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide is an acyclic polyamide.

### Claim 8 (depends on 1)

The silicone hydrogel of claim 1, wherein the first or second monofunctional hydroxyl substituted, poly(disubstituted siloxane) comprises a monofunctional hydroxyl substituted, poly(dimethylsiloxane) of any of Formulae VIIa-IXb:
wherein R1 is methyl or H; n is between 4 and 30; wherein Z is selected from O, N, S or NCH2CH2O, when Z is O or S R2 is not present;
R2 is independently selected from the group consisting of a linear, branched, or cyclic alkyl group containing one to eight carbon atoms, any of which may be further substituted with at least one hydroxy group, and which may be optionally substituted with amide, ether, and combinations thereof;
n1 and n2 are independently between 4 to 100;
n3 is 1-50;
R5 is selected from straight or branched C1 to C8 alkyl groups, which may be optionally substituted with one or more hydroxyl, amide, ether, polyhydroxyl groups selected from straight or branched C1 to C8 groups having a formula of CfHg(OH)h wherein f=1-8 and g+h=2f+1 and cyclic C1 to C8 groups having a formula of CfHg(OH)h wherein f=1-8 and g+h=2f−1, and combinations thereof;
a is 4-8 for the first hydroxyl-containing silicone component and between 4-100 for the second hydroxyl-containing silicone component.

### Claim 9 (depends on 1)

The silicone hydrogel of claim 1 wherein the second hydroxyl substituted, poly(disubstituted siloxane)s comprises mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminated mono-n-butyl terminated polydimethylsiloxane (OH-mPDMS) having fifteen siloxane repeating units.

### Claim 10 (depends on 1)

The silicone hydrogel of claim 1, wherein the hydrophilic monomer comprises a reactive group selected from the group consisting of (meth)acrylates, (meth)acrylamides, styrenes, N-vinyllactams, N-vinylamides, O-vinylcarbamates, O-vinylcarbonates, vinyl ethers, vinyl esters, vinyls, allyls and combinations thereof.

### Claim 11 (depends on 1)

The silicone hydrogel of claim 1 further comprising at least one charged monomer.

### Claim 12 (depends on 1)

The silicone hydrogel of claim 1, wherein the hydrophilic monomer is present in the reactive monomer mixture in an amount between about 15 to about 35 wt %.

### Claim 13 (depends on 1)

The silicone hydrogel of claim 1, wherein the hydrophilic monomer is selected from hydrophilic amide monomers.

### Claim 14 (depends on 13)

The silicone hydrogel of claim 13, wherein the reactive monomer mixture comprises less than about 30 wt % hydrophilic amide monomers.

### Claim 15 (depends on 1)

The silicone hydrogel of claim 1, wherein the hydrophilic monomer is selected from the group consisting of N,N-dimethylacrylamide, acrylamide, ethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether (DEGVE), N-vinyl pyrrolidone (NVP), 1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone, N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-methyl acetamide (VMA), N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, allyl alcohol, N-vinyl caprolactam, N-2-hydroxyethyl vinyl carbamate, N-carboxy-ß-alanine N-vinyl ester; N-carboxyvinyl-β-alanine (VINAL), N-carboxyvinyl-α-alanine and mixtures thereof.

### Claim 16 (depends on 1)

The silicone hydrogel of claim 1, wherein the hydrophilic monomer is selected from N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, N-vinyl acetamide, and 1-methyl-5-methylene-2-pyrrolidone.

### Claim 17 (depends on 1)

The silicone hydrogel of claim 1, wherein the hydrophilic monomer comprises N-vinylpyrrolidone, N,N-dimethylacrylamide, or mixtures thereof.

### Claim 18 (depends on 1)

The silicone hydrogel of claim 1, wherein the silicone hydrogel has an oxygen permeability (Dk) of at least about 80 barrers.

### Claim 19 (depends on 11)

The silicone hydrogel of claim 11, wherein the charged monomer comprises at least one ionic moiety selected from the group consisting of anions, cations, zwitterions, betaines, and mixtures thereof.

### Claim 20 (depends on 19)

The silicone hydrogel of claim 19, wherein the charged monomer comprises at least one polymerizable group.

### Claim 21 (depends on 19)

The silicone hydrogel of claim 19, wherein the charged monomer comprises at least one carboxylic acid group.

### Claim 22 (depends on 21)

The silicone hydrogel of claim 21, wherein the charged monomer comprises at least one carboxylic acid monomer selected from the group consisting of (meth)acrylic acid, furmaric acid, maelic acid, itaconic acid, crotonic acid, cinnamic acid, vinylbenzoic acid, monoesters of furmaric acid, maelic acid, and itaconic acid, and mixtures thereof.

### Claim 23 (depends on 21)

The silicone hydrogel of claim 21, wherein the charged monomer comprises mixture of anionic and cationic monomer.

### Claim 24 (depends on 21)

The silicone hydrogel of claim 21, wherein the charged monomer is selected from the group consisting of (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopropanoic acid (ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA), 2-(methacryloyloxy)ethyl trimethylammonium chloride (Q Salt), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), 1-propanaminium, N-(2-carboxyethyl)-N, N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-, inner salt (CBT, carboxybetaine), 1-propanaminium, N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-, inner salt (SBT, sulfobetaine), 3,5-Dioxa-8-aza-4-phosphaundec-10-en-1-aminium, 4-hydroxy-N,N,N-trimethyl-9-oxo-, inner salt, 4-oxide (9CI) phosphobetaine(PBT), 2-methacryloyloxyethyl phosphorylcholine, 3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS), 3-((3-acrylam idopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS), 3-((3-methacrylam idopropyl)dimethylammonio)propane-1-sulfonate (MAMPDAPS), 3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS), methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS), and mixtures thereof.

### Claim 25 (depends on 21)

The silicone hydrogel of claim 21, wherein the charged monomer is selected from the group consisting of (meth)acrylic acid, N-[(ethenyloxy)carbonyl]-β-alanine (VINAL), 3-acrylamidopropanoic acid (ACA1), 5-acrylamidopropanoic acid (ACA2), and mixtures thereof.

### Claim 26 (depends on 11)

The silicone hydrogel of claim 11, wherein the at least one charged monomer comprises up to about 5 wt %, based on the total weight of the reactive monomer mixture.

### Claim 27 (depends on 11)

The silicone hydrogel of claim 11, wherein the charged monomer is selected from acrylic acid, methacrylic acid, and mixtures thereof.

### Claim 28 (depends on 1)

The silicone hydrogel of claim 1 wherein the polyamide comprises an acyclic polyamide selected from the group consisting of PVMA, PNVA, and poly[N-vinyl N-alkyl acetamide]s wherein the N-alkyl group is selected from the group consisting of linear and branched alkyl groups containing between one and five carbon atoms, and copolymers and mixtures thereof.

### Claim 29 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide comprises poly(N-vinyl-N-methyl acetamide), poly(N-vinyl acetamide), polydimethylacrylamide, or a mixture of two or more thereof.

### Claim 30 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide comprises a copolymer.

### Claim 31 (depends on 30)

The silicone hydrogel of claim 30, wherein the copolymer comprises repeating units selected from the group consisting of N-vinyl amides, acrylamides, hydroxyalkyl(meth)acrylates, alkyl(meth)acrylates, N-vinylpyrrolidone, N,N-dimethylacrylamide, 2-hydroxyethylmethacrylate, vinyl acetate, acrylonitrile, hydroxypropyl methacrylate, 2-hydroxyethyl acrylate, methyl methacrylate, butyl methacrylate, methacryloxypropoyl tristrimethylsiloxysilane, siloxane substituted acrylates or methacrylates, and mixtures thereof.

### Claim 32 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide comprises repeating units of Formula I or Formula II
wherein X is a direct bond, —(CO)—, or —(CO)—NHRe—, wherein Re is a C1 to C3 alkyl group;
Ra is selected from H, straight or branched, substituted or unsubstituted C1 to C4 alkyl groups;
Rb is selected from H, straight or branched, substituted or unsubstituted C1 to C4 alkyl groups, amino groups having up to two carbon atoms, amide groups having up to four carbon atoms, and alkoxy groups having up to two carbon atoms;
Rc is selected from H, straight or branched, substituted or unsubstituted C1 to C4 alkyl groups, ethoxy, hydroxyethyl, and hydroxymethyl;
Rd is selected from H, straight or branched, substituted or unsubstituted C1 to C4 alkyl groups ethoxy, hydroxyethyl, and hydroxymethyl;
wherein the number of carbon atoms in Ra and Rb taken together is 8 or less, and wherein the number of carbon atoms in Rc and Rd taken together is 8 or less.

### Claim 33 (depends on 32)

The silicone hydrogel of claim 32, wherein the polyamide is a copolymer comprising at least about 80 mole % of the repeating units from Formula I or Formula II.

### Claim 34 (depends on 32)

The silicone hydrogel of claim 32, wherein Rb is selected from straight or branch unsubstituted C1 to C4 alkyl groups.

### Claim 35 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide comprises between about 3 and 15 wt % of the reactive monomer mixture, based upon all reactive components.

### Claim 36 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide comprises between about 3 and 12 wt % of the reactive mixture based upon all reactive components.

### Claim 37 (depends on 1)

The silicone hydrogel of claim 1, wherein the polyamide comprises a cyclic polyamide.

### Claim 38 (depends on 37)

The silicone hydrogel of claim 37, wherein the cyclic polyamide comprises polyvinylypyrrolidone (PVP) in an amount up to about 15 wt. %.

### Claim 39 (depends on 1)

The silicone hydrogel of claim 1, wherein the reactive monomer mixture further comprises at least one additional constituent selected from the group consisting of a diluent, a UV absorbing compound, a medicinal agent, an antimicrobial compound, a pharmaceutical compound, a nutraceutical compound, a photochromic compound, a reactive tint, a pigment, a copolymerizable dye, a nonpolymerizable dye, a release agent, a copolymer, and combinations thereof.

### Claim 40 (depends on 1)

The silicone hydrogel of claim 1 further comprising at least one hydroxylalkyl (meth)acrylate monomer.

### Claim 41 (depends on 40)

The silicone hydrogel of claim 40 wherein said hydroxyalkyl (meth)acrylate monomer is selected from the group consisting of 2-hydroxyethyl (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 1-hydroxypropyl-2-(meth)acrylate, 2-hydroxy-2-methyl-propyl (meth )acrylate, 3-hydroxy-2,2-dimethyl-propyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, glycerol (meth)acrylate, polyethylene glycol monomethacrylate, and mixtures thereof.

### Claim 42 (depends on 40)

The silicone hydrogel of claim 40 wherein said hydroxyalkyl (meth)acrylate monomer is selected from the group consisting of 2-hydroxyethyl methacrylate, glycerol methacrylate, 2-hydroxypropyl methacrylate, hydroxybutyl methacrylate, 3-hydroxy-2,2-dimethyl-propyl methacrylate, and mixtures thereof.

### Claim 43 (depends on 40)

The silicone hydrogel of claim 40 wherein said hydroxyalkyl (meth)acrylate monomer is selected from the group consisting of 2-hydroxyethyl methacrylate, 3-hydroxy-2,2-dimethyl-propyl methacrylate, hydroxybutyl methacrylate or glycerol methacrylate.

### Claim 44 (depends on 1)

A contact lens comprising the silicone hydrogel of claim 1.

### Claim 45 (depends on 44)

The contact lens of claim 44, wherein the lysozyme uptake is at least about 50 μg/lens.

### Claim 46 (depends on 44)

The contact lens of claim 44, wherein the lipid uptake is less than about 15 μg/lens.

### Claim 47 (depends on 44)

The contact lens of claim 44, wherein the lipid uptake is less than 10 μg/lens.

### Claim 48 (depends on 45)

The contact lens of claim 45, wherein the PQ1 uptake is less than about 20%.

### Claim 49 (depends on 47)

The contact lens of claim 47, wherein the PQ1 uptake is less than 10%.

### Claim 50 (depends on 44)

The contact lens of claim 44, wherein the lysozyme uptake is at least about 100 μg/lens, the lipid uptake is less than 10 μg/lens, and the PQ1 uptake is less than 10%.

### Claim 51 (depends on 44)

The contact lens of claim 44, wherein the dynamic contact angle is less than about 60°.

### Claim 52 (depends on 44)

The contact lens of claim 44, wherein the Dk is greater than about 80 barrers, wherein the lysozyme uptake is greater than about 50 μg/lens, wherein the lipid uptake is less than about 10 μg/lens; wherein the PQ1 uptake is less than about 15%;
and wherein the contact angle is less than about 50°.

### Claim 53 (depends on 44)

The contact lens of claim 44 comprising lipid uptake of less than about 10μg/lens and an advancing contact angle of less than about 70°.

### Claim 54 (depends on 1)

The silicone hydrogel of claim 1, wherein the reactive monomer mixture further comprises at least one additional silicone-containing compounds without hydroxyl functionality.

### Claim 55

A silicone hydrogel formed from a reactive monomer mixture comprising:
a) between about 1 and about 15 wt % at least one polyamide;
b) at least one hydroxyl silicone-containing monomer;
c) at least one hydroxyl substituted poly(disubstituted siloxane) selected from the group consisting of monofunctional poly(disubstituted siloxane) having 4 to 8 siloxane repeating units, and monofunctional hydroxyl substituted poly(disubstituted siloxane)s having 10 to 200 siloxane repeating units, and mixtures thereof;
d) about 5 to about 25 wt % at least one hydrophilic monomer;
wherein the first hydroxyl substituted poly(disubstituted siloxane) and the second monofunctional hydroxyl substituted poly(disubstituted siloxane) are present in concentrations to provide a ratio of wt % of all first hydroxyl substituted, linear poly(disubstituted siloxane) to wt % of all one second hydroxyl substituted poly(disubstituted siloxane)s of 0.4-1.3.