# US 2021/0332174 A1 · Hydrogel compositions

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- Number: US 2021/0332174 A1
- Document ID: US20210332174A1
- Status: Published application
- Kind: A1
- Application number: 17/282,209
- Filed: 2019-09-30
- Published: 2021-10-28
- Earliest claimed: 2018-10-02
- Assignees: Ophtalmic Compagnie; Universite De Haute Alsace
- Applicants: Ophtalmic Compagnie; Université de Haute-Alsace
- Inventors: Jean-François STUMBÉ; Romain JAGU; Jean-François RUMIGNY; Sophie BISTAC; Fanny COUMES
- Web page: https://patentgrep.com/patent/US20210332174A1

## CPC

- C08F 220/20: of polyhydric alcohols or phenols {, e.g. 2-hydroxyethyl (meth)acrylate or glycerol mono-(meth)acrylate}
- C08F 283/08: on to polyphenylene oxides
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/52: Hydrogels or hydrocolloids
- C08F 290/062: {Polyethers}
- C08G 65/3328: {heterocyclic}
- C08G 65/33351: {acyclic}
- G02B 1/043: {Contact lenses}
- G02C 7/04: Contact lenses for the eyes (disinfection or sterilisation of contact lenses A61L12/00)
- A61L 2430/16: for reconstruction of eye parts, e.g. intraocular lens, cornea
- C08F 2810/20: leading to a crosslinking, either explicitly or inherently
- C08G 65/2609: {containing aliphatic hydroxyl groups}
- C08G 65/332: containing carboxyl groups, or halides, or esters thereof
- C08G 65/33348: {containing isocyanate group}
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02C: SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES (trial frames for testing the eyes A61B3/04; goggles or eyeshields not having the same features as spectacles A61F9/00)

## Abstract

A crosslinkable composition comprising: A) at least one polymerisable monomer or a mixture of polymerisable monomers or a mixture of polymerisable monomers and macromonomers bearing at least one polymerisable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrene or vinyl type; B) at least one polyol chosen from oligoglycerols, linear, branched and hyperbranched polyglycerols, or a mixture of hyperbranched polyglycerol and a polyol chosen from oligoglycerols, and linear, branched and hyperbranched polyglycerols, comprising, on average, more than 1 hydroxyl group functionalised with a group bearing a polymerisable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrene or vinyl type; C) a free radical initiator or a mixture of free radical initiators capable of initiating polymerisation by thermal, redox or photochemical means; and D) optionally, at least one additive.

## Claims

### Claim 1

A crosslinkable composition comprising:
A) at least one polymerizable monomer or a mixture of polymerizable monomers or a mixture of monomers and polymerizable macromonomers bearing at least one polymerizable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrenic or vinylic type;
B) at least one polyol selected from oligoglycerols, linear, branched and hyperbranched polyglycerols, or a mixture of hyperbranched polyglycerol and of a polyol selected from the oligoglycerols, and the linear, branched and hyperbranched polyglycerols, comprising on average more than 1 hydroxyl group functionalized with a group bearing a polymerizable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrenic or vinylic type;
C) a radical initiator or a mixture of radical initiators that are able to initiate polymerization by thermal, redox or photochemical routes; and
D) optionally at least one additive selected from antioxidants, agents for adjusting the physicochemical properties, agents for promoting, modulating and/or controlling permeability to oxygen, plasticizers, moistening agents, lubricants, viscosity modifiers, compatibilizers, colorants, filtering agents, antimicrobial agents, therapeutic agents and agents against bacterial biofilms.

### Claim 2

A crosslinked composition able to form a hydrogel polymer, resulting from the crosslinking:
A) at least one polymerizable monomer or mixture of polymerizable monomers or a mixture of monomers and polymerizable macromonomers bearing at least one polymerizable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrenic or vinylic type;
B) at least one polyol selected from oligoglycerols, linear, branched and hyperbranched polyglycerols or a mixture of hyperbranched polyglycerol and of a polyol selected from oligoglycerols and linear, branched and hyperbranched polyglycerols, comprising on average more than 1 hydroxyl group functionalized with a group bearing a polymerizable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrenic or vinylic type;
C) a radical initiator or a mixture of radical initiators capable of initiating polymerization by thermal, redox or photochemical routes; and
D) optionally at least one additive selected from antioxidants, agents for adjusting the physicochemical properties such as Young's modulus, elongation at break and breaking stress, agents for promoting, modulating and/or controlling permeability to oxygen, plasticizers, moistening agents, lubricants, viscosity lowering agents, compatibilizers, colorants, filtering agents, antimicrobial agents, therapeutic agents and agents against bacterial biofilms.

### Claim 3 (depends on 1)

The composition as claimed in claim 1, in which the functionalized hyperbranched polyglycerol is obtained from a hyperbranched polyglycerol having a molecular weight between 546 and 100 000 g/mol, and has a degree of branching (DB) between 0.3 and 1.0.

### Claim 4 (depends on 1)

The composition as claimed in claim 1, in which the hyperbranched polyglycerol is a polyglycerol dendrimer or a hyperbranched polyglycerol with a degree of branching between 0.3 and 1.0, or a mixture of hyperbranched polyglycerol and of oligoglycerols or of linear polyglycerols.

### Claim 5 (depends on 1)

The composition as claimed in claim 1, in which the polymerizable C═C function on the functionalized hyperbranched polyglycerol is selected from the acrylic, methacrylic, maleic, fumaric, itaconic, citraconic or vinylic groups of structure:
in which R1 represents H or methyl; R2 represents H, linear or branched C1-6alkyl, or —C(═O)OR2A in which R2A represents H or linear or branched C1-6alkyl optionally substituted with one or more hydroxyl groups, and R3 represents H, linear or branched C1-20 alkyl.

### Claim 6 (depends on 1)

The composition as claimed in claim 1, in constituent B), the polymerizable C═C function of the acrylate or methacrylate type is selected from acrylic acid, methacrylic acid, alkyl (meth)acrylates and derivatives thereof, such as 2-hydroxyethylmethacrylate (HEMA), 2-hydroxyethylacrylate (HEA), methylmethacrylate (MMA), methacrylamide, N,N-dimethyl-diacetoneacrylamide, 2-phosphatoethylmethacrylate, mono-, di-, tri-, tetra-, penta-polyethylene glycol acrylates or methacrylates, N-(3-methacrylamidopropyl)-N,N-dimethylamine, N-(3-methacrylamidopropyl)-N,N,N-trimethylamine, N-(3-acrylamido-3-methylbutyl)-N,N-dimethylamine, N-methacrylamide, 3-hydroxypropyl methacrylate, propyl methacrylate, propyl acrylate, butyl methacrylate, butyl acrylate, pentyl acrylate, pentyl methacrylate, N-(1,1-dimethyl-3-oxobutyl)acrylamide, 2-ethyl-2-(hydroxy-methyl)-1,3-propanediol trimethacrylate, butyl(meth)acrylate, 2-hydroxybutyl methacrylate, 3-hydroxy-2-naphthyl methacrylate, N-(formylmethyl)acrylamide, 2-ethoxyethyl methacrylate, 4-t-butyl-2-hydroxycyclohexyl methacrylate, the isocyanatoalkyl(meth)acrylates such as 2-isocyanatoethylmethacrylate, 2-isocyanatoethyl acrylate, and a compound selected from 4-[(a)-phenyl diazenyl]phenyl-2-methacrylate (4-[(E)-phenyldiazenyl]phenyl-2-methacrylate) and 4-[(a)-phenyl diazenyl]phenyl-2-methacrylate (4-[(E)-phenyldiazenyl]phenyl-2-methacrylate).

### Claim 7 (depends on 6)

The composition as claimed in claim 6, in which the polymerizable C═C function is an isocyanatoalkyl(meth)acrylate.

### Claim 8 (depends on 7)

The composition as claimed in claim 7, in which the isocyanatoalkyl(meth)acrylate is selected from 2-isocyanatoethylmethacrylate and 2-isocyanatoethylacrylate or a mixture thereof.

### Claim 9 (depends on 1)

The composition as claimed in claim 1, in which constituent A) is selected from:
acrylic acid or methacrylic acid as well as alkyl (meth)acrylates and derivatives thereof, such as 2-hydroxyethylmethacrylate (HEMA), 2-hydroxyethylacrylate (HEA), methylmethacrylate (MMA), methacrylamide, N,N-dimethyl-diacetoneacrylamide, 2-phosphatoethylmethacrylate, mono-, di-, tri-, tetra-, penta-polyethylene glycol acrylates or methacrylates, N-(3-methacrylamidopropyl)-N,N-dimethylamine, N-(3-methacrylamidopropyl)-N,N,N-trimethylamine, N-(3-acrylamido-3-methylbutyl)-N,N-dimethylamine, N-methacrylamide, 3-hydroxypropyl methacrylate, propyl methacrylate, propyl acrylate, butyl methacrylate, butyl acrylate, pentyl acrylate, pentyl methacrylate, N-(1,1-dimethyl-3-oxobutyl)acrylamide, 2-ethyl-2-(hydroxy-methyl)-1,3-propanediol trimethacrylate, butyl(meth)acrylate, 2-hydroxybutyl methacrylate, 3-hydroxy-2-naphthyl methacrylate, N-(formylmethyl)acrylamide, 2-ethoxyethyl methacrylate, 4-t-butyl-2-hydroxycyclohexyl methacrylate, or the isocyanatoalkyl(meth)acrylates such as 2-isocyanatoethylmethacrylate, 2-isocyanatoethyl acrylate, 4-[(a)-phenyl diazenyl]phenyl-2-methacrylate (4-[(E)-phenyldiazenyl]phenyl-2-methacrylate) or 4-[(a)-phenyl diazenyl]phenyl-2-methacrylate (4-[(E)-phenyldiazenyl]phenyl-2-methacrylate),
the maleate and fumarate monomers, such as maleic acid, maleic anhydride, dimethyl maleate, diethyl maleate, or the higher maleate esters in which the alkyl chain contains 3 to 20 carbon atoms as well as fumaric acid, dimethyl fumarate, diethyl fumarate or the higher fumarate esters in which the alkyl chain contains 3 to 20 carbon atoms,
the itaconate monomers; such as itaconic acid, itaconic anhydride, dimethyl itaconate, or the higher itaconate esters in which the alkyl chain contains 3 to 20 carbon atoms,
the citraconate monomers; such as citraconic acid, citraconic anhydride, dimethyl citraconate, or the higher citraconate esters in which the alkyl chain contains 3 to 20 carbon atoms,
the (meth)acrylic monomers that may contain silicone or silane functions; for example tris(trimethylsiloxy)silylpropyl methacrylate, bis(trimethylsiloxy)methylsilylpropyl methacrylate, pentamethyldisiloxanepropyl methacrylate, tris(trimethylsiloxy) silylpropyloxyethyl methacrylate, tris(trimethylsiloxy)-silylpropyl methylacryloxyethylcarbamate, tris(trimethylsiloxy)silylpropylglycerol methacrylate, phenyltetramethyl-disiloxanylethyl acrylate, 3-methacryloxypropylbis(trimethylsiloxy)methylsilane, methyl-di(trimethylsiloxy)methacryloxymethyl silane, (3-methacryloxy-2-hydroxypropyloxy) propyl bis(trimethylsiloxy)methylsilane, 3-acryloxypropyl tris(trimethylsiloxy)silane, 3-acryloxypropyltrichlorosilane, 3-methacryloxypropyl dimethyl ethoxysilane, 3-methacryloxypropyl methyl diethoxysilane, methacryloxypropylbis(trimethylsiloxy)methylsilane, tristrimethylsilyloxysilylpropyl methacrylate, bis(methacryloxypropyl) tetramethyldisiloxane, acryloxymethyltrimethylsilane, p-(t-butyldimethylsiloxy)styrene, 1,3-bis(3-methacryloxypropyl)tetrakis(trimethylsiloxy)disiloxane, 3 trimethylsilylpropargylmethacrylate, 3-(trimethoxysilyl)propyl acrylate,
vinyl monomers, which may contain silicone or silane functions; for example vinyl(chloromethyl)dimethoxysilane, vinylethoxysiloxane-propylethoxysiloxane, vinyltris(1-methoxy-2-propoxy)silane, vinyltris(2-methoxyethoxy)silane, vinyltrimethoxysilane, vinyltriisopropoxysilane, vinyltriethoxysilane, vinyltrichlorosilane, vinyl tri-t-butoxysilane, o-(vinyloxybutyl)-n-triethoxysilylpropyl carbamate, vinylmethyldimethoxysilane, vinylmethyldiethoxysilane, vinyldimethylethoxysilane, 3-[tris(trimethylsiloxy)silyl] propylvinyl carbamate, triethoxysilylpropyl maleic acid or 1,3,5-trivinyl-1,1,3,5,5-pentamethyltrisiloxane,
fluorinated acrylic and methacrylic monomers, such as dihydroperfluorooctyl acrylate, 1,1-dihydroperfluorobutyl acrylate, trihydroperfluoroalkyl acrylate, tetrahydroperfluoroalkylacrylate, tris(trimethylsilyloxy)propyl methacrylate, perfluoro hexylethylthiocarbonylaminoethyl methacrylate, trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, hexafluorobutyl methacrylate, trifluoroethyl methacrylate,
organosilane prepolymer compounds, such as □□ω-bismethacryloxy-propyl polydimethylsiloxane, polydimethylsiloxanes with vinylic termination(s), diphenylsiloxane-dimethylsiloxane copolymers with a vinylic termination, trifluoropropylmethylsiloxane copolymers with vinylic termination(s), diethylsiloxane-dimethylsiloxane copolymers with vinylic termination(s), ethylsiloxane-dimethylsiloxane copolymers with vinylic termination(s), ethylene-siloxane copolymers with vinylic termination(s), tris(polydimethylsiloxy)silylpropyl methacrylate, polysiloxanylalkyl (meth)acrylates, methacryloxypropyl with polydimethylsiloxane termination, 1,3-divinyl-1,1,3,3-tetramethyldisiloxane, 2-(divinylmethylsilyl)ethyltriethoxysilane, or 1,3-divinyl-1,3-diphenyl-1,3-dimethyldisilane,
fluorinated/silane or chlorinated/silane mixed compounds, such as fluoro-methacryloxypropyl tris(trimethylsiloxy) silane, 3-acryloxy propyl methyl dichlorosilane, 3-acryloxypropyltrichlorosilane, 3-methacryloxypropyl trichlorosilane,
the silane/isocyanate compounds such as 3-isocyanatopropyltriethoxysilane, and
vinyl monomers, such as N-vinyl lactams; for example N-vinyl pyrrolidone (NVP)), N-vinyl-N-methyl acetamide (VMA), N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, N-2-hydroxyethyl vinyl carbamate, N-carboxy-alanine N-vinyl ester, preferably CH3C(O)N(CH3)-CH═CH2 (N-vinyl-N-methyl acetamide (VMA)).

### Claim 10 (depends on 1)

The composition as claimed in claim 1, in which the initiator is at least one UV, thermal and/or redox initiator, selected from:
a photochemical initiator selected from the group comprising 2-hydroxy-4-acryloyloxyethoxy benzophenone, 2-hydroxy-4-(2-hydroxy-3-methacrylyloxy) propoxybenzophenone; benzophenone, acetophenone, acetonaphthoquinone, methyl ethyl ketone, valerophenone, hexanophenone, C-phenylbutyrophenone, p-morpholinopropiophenone, dibenzosuberone, 4-morpholinobenzophenone, 4-morpholinodeoxybenzoin, p-diacetylbenzene, 4-aminobenzophenone, para-methoxyacetophenone, 3-methylanthraquinone, tert-butylanthraquinone, the esters of anthraquinone, benzaldehyde, 9-acetylphenanthrene, 2-acetylphenanthrene, 10-thioxanthenone, 3-acetylphenanthrene, 3-acetylindole, 9-fluorenone, 1-indanone, 1,3,4-triacetylbenzene, thioxanthen-9-one, xanthen-9-one, 2,4-dimethylthioxanthone, 2,4-diethylthioxanthone, 2,4-diisopropylthioxanthone, 2,4-dichlorothioxanthone, benzoin, benzoin isobutyl ether, benzoin tetrahydropyranyl ether, benzoin methyl ether, benzoin ethyl ether, benzoin butyl ether, benzoin isopropyl ether, chloroxanthenone, 7-H-benzoin methyl ether, benzodeanthracen-7-one, 1-naphthaldehyde, 4,4′-bis(dimethylamino)benzophenone, 4-phenylbenzophenone, 4-chlorobenzophenone, 4,4′-bis(dimethylamino)benzophenone, 1-acetonaphthone, 2-acetonaphthone, 1-benzoylcyclohexan-1-ol, 2-hydroxy-2,2-dimethylacetophenone, 2′2-dimethoxy-2-phenylacetophenone, 2,2-diethoxy-2-phenylacetophenone, 1,1-dichloroacetophenone, 1-hydroxyacetophenone, acetophenone dimethyl acetal, o-methoxybenzophenone, triphenylphosphine, tris-o-tolylphosphine, benzaanthracene-7,12-dione, 2,2-diethoxyacetophenone, the benzyl acetals such as benzyl dimethyl acetal, 2-methyl-1-4-(methylthio)phenyl-2-morpholinopropan-1-one, the anthraquinones such as 2-methylanthraquinone, 2-ethylanthraquinone, 2-tert-butylanthraquinone, 1-chloroanthraquinone, 2-amylanthraquinone, 2,3-butanedione,
a photoinitiator selected from the group comprising esters of phenylglyoxalic acid, and combinations thereof with one another or with promoters of photopolymerization such as benzoic acid or amines,
a thermal initiator selected from the group comprising 2,2-azobis(2,4-dimethylpentanenitrile), 2,2′-azobisisobutyronitrile, 1,1′-azobis(cyclohexanecarbonitrile), 2,2′-azobis(2-methylpropionitrile), potassium peroxodisulfate, dibenzoyl peroxide, cyclohexanone peroxide, di-tert-butyl peroxide, acetyl cyclohexylsulfonyl peroxide, diisopropyl percarbonate, tert-butyl peroctoate or benzpinacol, di-t-butyl peroxide, cumene hydroperoxide, dicumyl peroxide, t-butyl perbenzoate, and hydroxylated N-oxide amine, such as 2,2,6,6-tetramethylpiperidine-N-oxyl and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl,
a redox initiator system selected from the group comprising oxidants such as AIBN, the peroxides such as hydrogen peroxide, benzoyl peroxide, t-butyl-hydroperoxide, p-mentane hydroperoxide, ammonium persulfate, sodium persulfate, potassium persulfate, reducing agents such as ascorbic acid, sodium bisulfite, N,N,N′,N′-tetramethylethylene diamine formaldehyde sodium sulfoxylate, the Fe2+, Cr2+, Zn2+, V2+, Ti3+, CO2+, Cu+ metal salts such as iron sulfate, and the N,N-dialkylanilines such as N,N-dimethyl-p-toluidine.

### Claim 11 (depends on 1, 2)

A hydrogel obtainable by:
hydration/swelling, from water or an aqueous solution, of a crosslinked composition as claimed in claim 2, or,
polymerization of the crosslinkable composition as claimed in claim 1, in the presence of a water-miscible protic or aprotic solvent, and then exchange of the solvent with an excess of water or an aqueous solution, or
by polymerization of the crosslinkable composition as claimed in claim 1, in the presence of water or an aqueous solution.

### Claim 12 (depends on 2)

A method for preparing a crosslinked composition as defined in claim 2 consisting of reacting, in the presence or absence of aprotic solvent, preferably in the absence of solvent:
A) at least one polymerizable monomer or mixture of polymerizable monomers or a mixture of monomers and polymerizable macromonomers bearing at least one polymerizable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrenic or vinylic type
B) at least one polyol selected from oligoglycerols and linear, branched and hyperbranched polyglycerols, or a mixture of hyperbranched polyglycerol and of a polyol selected from oligoglycerols and linear, branched and hyperbranched polyglycerols, comprising on average more than 1 hydroxyl groups functionalized with a group bearing a polymerizable C═C function of the acrylate, methacrylate, maleate, fumarate, itaconate, citraconate, styrenic or vinylic type;
C) a radical initiator or a mixture of radical initiators that are able to initiate polymerization by thermal, redox or photochemical routes; and
D) optionally at least one additive selected from antioxidants, agents for adjusting the physicochemical properties such as Young's modulus, elongation at break and breaking stress, promoters of permeability to oxygen, plasticizers, moistening agents, lubricants, viscosity modifiers, compatibilizers, colorants, filtering agents, antimicrobial agents, therapeutic agents and agents against bacterial biofilms.

### Claim 13 (depends on 12)

The method as claimed in claim 12, in which the functionalized hyperbranched polyglycerol is present at a rate from 0.1 to 99.99% by weight of the total weight of constituents A) to D), or in which the initiator is present at a rate from 0.02 to 5% by weight of the total weight of constituents A) to D).

### Claim 14 (depends on 12)

The method as claimed in claim 12, further comprising a step of molding the crosslinked composition.

### Claim 15 (depends on 12)

An article obtainable by the method as claimed in claim 12.

### Claim 16 (depends on 15)

The article as claimed in claim 15, which is selected from a contact lens or intraocular lens, a patch, an implant or a dressing.

### Claim 17 (depends on 1)

The use of a composition or of a hydrogel as claimed in claim 1 for manufacturing a medical device, or as a vector of a compound of interest selected from therapeutic active ingredients, vitamins, nutrients, decontaminating agents or lubricants, or in biomedical, cosmetic, or health-related applications.

### Claim 18

The use of a hyperbranched polyglycerol comprising on average more than one group, preferably at least 2 hydroxyl groups functionalized with a group bearing a polymerizable C═C function, as crosslinking agent, comonomer or principal monomer for manufacturing a contact lens or intraocular lens.