ES2345595B1 - HYDROPHILE ACRYLIC SYSTEMS OF ELEVATE REFRACTION INDEX FOR PREPARATION OF INTRAOCULAR LENSES. - Google Patents

Abstract

High index hydrophilic acrylic systems of refraction for preparation of intraocular lenses.

The present invention describes the preparation of high refractive acrylic hydrophilic systems and Bactericidal properties for the manufacture of intraocular lenses Flexible (IOL) that can be inserted through small incisions The intraocular lenses molded from these materials can be made thinner or reduced in diameter with relationship to known flexible intraocular lenses, allowing reduce the incision necessary for their implantation. In addition, these systems have antiseptic properties against specific strains of the eye environment.

Description

High index hydrophilic acrylic systems of refraction for preparation of intraocular lenses.

This present invention relates to the Preparation of hydrophilic acrylic systems of high index of refraction suitable for the manufacture of intraocular lenses Flexible (IOL) that are used in minimally invasive surgery to Cataract treatment.

State of the art

Cataract surgery consists of lens removal when it becomes partially opaque or loses flexibility with age and is one of the most common in developed countries in people over 65, operation that is usually combined with lens implantation intraocular (IOL). The implantation of the lens allows to restore the refractive abilities of the eye.

Currently the use of soft lenses that can be folded and implanted through 3.5 mm incisions You can say that it is widespread due to the advantages that supposed. Lenses of this type have been manufactured from different materials among which it should be noted for its greater impact, the silicone lenses and acrylic lenses, and of these two types, the Acrylic lenses have some advantages, since they can bend in a more controllable way than silicone, and due to the high refractive index of acrylic materials, the lenses can get to be manufactured with thinner thicknesses. So, in the market You can find two types of soft acrylic lenses. Those that are formed by flexible materials but that present degrees of hydration below 1%, or those that are formed of poly (methacrylate) hydrogels 2-hydroxyethyl) (PHEMA) with degrees of hydration About 20% in water. Within the first type, they have been manufactured lenses based on acrylate copolymers of 2-phenethyl - methacrylate 2-phenethyl (PEA / PEMA) marketed under the name of Alcon Acrylsof®, or based on copolymers of ethyl acrylate - ethyl methacrylate - methacrylate 2,2,2-Trifluoroethyl (EA / EMA / TFEMA) marketed with the name of Allergan Clariflex®, with refractive indices of 1.55 and 1.47, respectively. Within the second type are PHEMA lenses that have a degree of hydration around of 38% and a refractive index of 1.41 (Alcon HydroSof®). These lenses have been modified by introducing other monomers hydrophobic acrylics to increase the refractive index, and in Some cases flexibility. This is how lenses of copolymers of HEMA with methyl methacrylate (HEMA / MMA) with a refractive index of 1.47 and degree of hydration of 20% marketed under the name ORC MemoryLens®, and copolymers of HEMA with 6-hydroxyhexyl methacrylate (HEMA / HEXMA) with a refractive index of 1.47 and a hydration of 18% (Storz Hydroview®).

Various materials for the preparation of intraocular lenses that attempt to reach a compromise between the degree of hydration and the refractive index have developed in recent years either by introducing hydrophobic monomers or by introducing hydrophilic monomers, and some of these Materials are patented. Hydrophobic comonomers of high refractive index that have been used in the preparation of intraocular lenses are methacrylates with aromatic groups (US Patent US5693095) that give rise to copolymers with a refractive index of 1.53 in the hydrated state or methacrylates with ethenylaromatic groups (US Patent US 2007010883) which give rise to copolymers with a refractive index of 1.52 to 1.55 once hydrated. Aromatic hydrophobic comonomers derived from aniline, benzylamine, phenol, phenylmethanol, phenylethanol, naphthol, benzylmercaptane and phenylethylmercaptan (US Pat. No. US2002037984) have also been used which give copolymers with a refractive index of 1.46 to 1.52 in the dry state, as well as comonomers hydrophobes derived from phenol and thiophenol (WO2007062864) and those derived from phenoxyethanol and thiophenoxyethanol (WO2007094664). High refractive hydrophilic comonomers that have been used in the preparation of soft intraocular lenses are those derived from functionalized phenylethanol in the para position of the aromatic ring (WO2006130402), those derived from N- benzyl- N- methylacrylamide (US Patent US 5717049 ) which give rise to copolymers having a refractive index of 1.42 to 1.49 in the hydrated state. US5480950 describes the use of hydrophilic comonomers of N- vinylpyrrolidone and 2,3, or 4-vinylpyridine together with diacrylic esters, which give rise to copolymers having a refractive index of 1.42 to 1.49 in the hydrated state, and US 5439950 describes the use of hydrophilic vinyl comonomers of heterocycles such as 4,6-divinylpyrimidine, 2,5-divinylpyrazine, 1.4 and 1.5-divinylimidazole which give copolymers having a refractive index of 1.40 to 1.60 in the hydrated state. .

On the other hand, post-surgical endophthalmitis remains one of the most important complications of cataract surgery. The bacterial adhesion that follows the implantation of the intraocular lens is one of its main causes. The adhesion is followed by bacterial proliferation until several layers of microcolonies are formed that constitute the basic structure of the subsequent biofilm . Once formed, the biofilm can survive the attack of antibiotics in concentrations of one hundred or a thousand times higher than those isolated by the same species can withstand so that, at this stage, the only way to attack the infection is to extract the infected infraocular lens. Therefore, preventing bacterial adhesion has been considered as the first step that must be taken to attack post-surgical infections. Of the polymer compositions described above for use as IOLs, none of them have bactericidal activity. In order to obtain compositions with this activity, some surface modifications have been carried out in commercial IOLs to give the surface of the lens bactericidal properties. Thus, PMMA IOLs with heparin have been superficially modified, marketed by Pharmacia Production BV that have demonstrated efficacy in reducing post-implantation bacterial adhesion (cf. AMA El-Asrar et al ., Intern Ophthalmol 21, 71-74, 1997 ). Hydrogel-like materials have also been superficially modified by electrostatic bonding of porphyrins to copolymers of HEMA with methacrylic acid or with 2-diethylamino ethyl methacrylate, with anionic or cationic pendant groups respectively (cf. C. Brady , et al ., J Phys Chem B 111, 527-534, 2007). Other developments have involved the coating of acrylic IOLs with copolymers of poly (2-methacryloxyethyl phosphoryl choline-co-n-butyl methacrylate) which has been effective in inhibiting the adhesion of both bacteria and fibroblasts (cf. M. Shigeta et al ., J Cataract Refract Surg 32, 859-866, 2006).

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Description of the invention

The present invention provides the preparation of hydrophilic acrylic systems of high refractive index and Bactericidal properties for the manufacture of infraocular lenses flexible comprising mainly a monomer or mixtures of high refractive hydrophilic acrylic monomers that they belong to the methacrylate halide family of n-alkylammonium and one or more acrylic monomers hydrophilic acrylate or methacrylate family of n-hydroxyalkyl. You can also understand others acrylate or methacrylate monomers that modulate flexibility and other methacrylate monomers bearing azol groups. These systems can also include a certain amount of an agent of UV absorption, polymerizable or not, as substituted benzophenones and Benzotriazoles

The present invention is related to the Preparation of hydrophilic acrylic systems of high index of refraction and bactericidal properties for lens manufacturing Flexible acrylic infraoculars.

These polymeric systems or compositions they have the following characteristics:

1.- Its high refractive index makes may decrease the thickness or diameter of intraocular lenses in relation to flexible acrylic infraocular lenses known in the state of the art, allowing, in this way, decrease the incision necessary for the implantation of the same.

2.- Halide-derived acrylic systems of n-alkylammonium methacrylates present bactericidal properties from ammonium salt quaternary, with activity against strains frequently found in the eye socket

3.- Halide-derived acrylic systems of n-alkylammonium methacrylates act as UV light filters

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Thus, a first aspect of the present invention refers to a polymeric composition consisting of a system hydrophilic acrylic with high refractive index and character bactericidal, hereinafter composition of the invention, comprising at least one monomer of general formula (I) and belonging to the acrylate or methacrylate halide family of n-alkylammonium and at least one acrylic monomer hydrophilic

The acrylate or methacrylate monomers of n-alkylammonium used in the present invention They belong to the general formula (I):

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one

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where:

n is a value of 1 to 12, preferably n is a value of 2, 3, 4, 5, or 6, more preferably n is 2;

X is an anion which is selected from the group comprising a halogen or a sulfonate,

R_ {1} is a hydrogen or a methyl group;

R2 and R 3 are the same or different from each other, and represent a radical (C 1 -C 3) alkyl.

R_ {4} is a aryl radical, substituted or unsubstituted, or an acetyl radical, substituted or unsubstituted.

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The term "alkyl" refers, in the present invention, to aliphatic, linear or branched chains, having 1 to 3 carbon atoms, for example, methyl, ethyl, n-propyl, i-propyl. Preferably the alkyl group is a methyl.

The term "aryl" refers to the present invention to an aromatic carbocyclic chain, which has 6 to 18 carbon atoms, being able to be single or multiple ring, in the latter case with separate and / or condensed rings. A non-limiting example of aryl is a phenyl, naphthyl group, anthracenyl or pyrenyl. Aryl radicals can be optionally substituted by one or more substituents such as halogen, hydroxyl amino, amido, ester, acyl, ether, thiol, alkoxy or thiol.

The term "acyl" refers, in the present invention, to a carboxylic acid derivative by elimination of a hydroxyl group. Acid derivatives carboxylic have as general formula R 5 -CO-, where R 5 is an aryl group with the above meanings, such as for example, but not limited to phenyl, naphthyl, anthracenyl or pyrenyl. Preferably R 5 is a phenyl or naphthyl group.

By "halogen" is meant herein invention to a bromine, chlorine, iodine or fluorine atom. Preferably The halogen is bromine.

By "sulphonate" is meant in the present invention an ion containing the functional group -SO 3 -. Its general formula is R 6 SO 3 -, where R 6 refers to linear or branched (C 1 -C 6) alkyl, aryl, substituted or unsubstituted groups . Non-limiting examples of sulfonate are the mesylate (methanesulfonate) ( MsO ) ion, the triflate (trifluoromethanesulfonate) ( TfO ) ion, the tosylate (p-toluenesulfonate) ( TsO ) ion or the nonafluorobutanesulfonate (ONf) ion.

A preferred embodiment of the composition of The invention comprises the monomers of formula (I) selected from the list comprising methacrylate bromide of 2- (N-benzyl, N, N-dimethylammonium) ethyl, methacrylate 2- (N-methylenenaphthyl, N, N-dimethylammonium) ethyl, methacrylate 2- (N-methylene pirenyl, N, N-dimethylammonium) ethyl, methacrylate 2- (N-Methylenacetophenyl, N, N-Dimethylammonium) ethyl methacrylate 2- (N-Methylenaketonephthyl, N, N-dimethylammonium) ethyl or any of its combinations.

In another preferred embodiment of the composition of the invention, the hydrophilic acrylic monomer is an acrylate and / or n-hydroxyalkyl methacrylate, or any of its combinations

Hydrophilic acrylate and / or monomers n-hydroxyalkyl methacrylates used in the Present invention belong to the general formula (II):

2

where:

n is a value of 0 to 4, preferably n is 2

m is a value of 0 to 1, preferably m is 0; Y

R_ {1} is a hydrogen or a methyl group.

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In a more preferred embodiment the monomer of formula (II) is 2-hydroxyethyl methacrylate (HEMA)

In another preferred embodiment of the composition of the invention, further comprising at least one acrylate monomer or methacrylate of general formula (III) that can modulate the flexibility of the final composition:

3

where:

n is 1 or 2,

R_ {1} is a hydrogen or a methyl group; Y

R2 is select from the list comprising a hydrogen, an alkyl (C 1 -C 6), aryl or an alkoxy.

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The term "alkoxy" refers, in the present invention, to a group of general formula R 7 -O-, where R 7 is an alkyl group with the above meanings and preferably refers to groups (C 1 -C 6) alkyl, linear or branched, or a aryl group with the previous meanings. As a group example alkoxy, but not limited to, are methoxy, ethoxy, propoxy, butoxy, phenoxy or naphthyloxy.

In a preferred embodiment, R2 of the general formula (III) is an alkyl, selected from the list that It comprises methyl, ethyl, propyl or butyl.

In another preferred embodiment, R2 of the General formula (III) is a phenyl or naphthyl.

In another preferred embodiment of the composition of the invention, the monomer of formula (III) is methacrylate of 2-ethoxyethyl, benzyl methacrylate, methacrylate 2-phenoxyethyl or any combination thereof.

In another preferred embodiment of the composition of the invention, further comprising at least one monomer of methacrylate carrier of azol groups, of general formula (IV),

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4

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where:

n is a value from 1 to 6, preferably n is a value of 1, 2, 3 or 4, more preferably n is 2, that is, the monomer of formula (IV) is methacrylate of (benzothiazolylthio) ethyl.

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In another preferred embodiment of the composition of the invention, further comprising a UV absorbing agent, which it can be polymerizable or not, preferably of the family of substituted benzophenones and benzotriazoles. These agents of UV absorption are compounds that absorb light of a wavelength less than 400 nm. This compound is incorporated into the mixture of monomers and gets trapped in the polymer matrix once it has been polymerization occurred. It is preferable to use a compound that apart from absorbing UV light it is also polymerizable, of this way the risk of leaching of the UV agent in the medium will be avoided Long-term biological.

A second aspect of the present invention is refers to a procedure for obtaining the composition of the invention comprising the following steps (from now on method of the invention):

i)

consists of mixing the monomers of the general formula (I) with the monomers of general formula (II) and optionally, monomers of general formula (III) and / or (IV) and / or absorption agents UV, with a radical polymerization initiator,

ii)

the reaction mixture from step (i) is deoxygenated,

iii)

it is then heat treated temperature between 45ºC and 70ºC, for the necessary time until achieve total conversion, and

iv)

subsequently the material is subjected to a post-cure at a temperature between 60ºC and 80ºC for a time between 24 and 96 hours. The post cured is a heat treatment at a temperature higher than the reaction with in order to react the residual monomer and eliminate some rest of reaction.

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In a preferred embodiment of the procedure of the invention, the compounds that are mixed in i) are one or several of the halide methacrylate monomers of n-alkylammonium of Formula (I) in an amount between 1-30% -p to maximize the refractive index and bactericidal power, one or more monomers acrylic hydrophilic of formula (II) in an amount comprised between 40-60% -p, one or more acrylic monomers of formula (III) in an amount between a 5-20% -p, and optionally, one or more monomers carriers of azol groups of formula (IV) in an amount between 1-30% -p and / or agents of UV absorption in a proportion preferably between 0.1-5% -p (by weight of the final composition).

In another embodiment of the procedure of the invention, the radical polymerization initiator is the azobisisobutyronitrile (AIBN) in a proportion between 0.3 and 2% in composition weight.

In another embodiment of the procedure of the invention, the reaction mixture of step (ii) is deoxygenated with nitrogen stream

In another preferred embodiment of the process of the invention, the mixture of step (ii) is subjected to heat treatment of 50-70 ° C for 16-24 hours and then post-curing at a temperature between 60-80 ° C for
24 h

In this way, by adding the mixture of reaction of step (ii) on cylindrical molds with subsequent demoulding in step iv) of the process of the invention, They can get small cylinders or rods. Starting at rods can be processed numerous discs that each have a thickness of approximately 4 mm. Although you can get disks from thicknesses between 0.5 and 4 mm depending on the volume of reaction used. These discs are suitable for manufacturing of flexible intraocular lenses, for implantation in the Cataract treatment with minimally invasive surgery.

Therefore, a third aspect of the present invention refers to the use of the composition of the invention as hydrophilic acrylic systems of high refractive index and bactericidal properties, for the manufacture of flexible lenses intraocular

Throughout the description and the claims the word "comprises" and its variants not they intend to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and features of the invention will be partly detached of the description and in part of the practice of the invention. The following examples and figures are provided by way of illustration, and are not intended to be limiting of the present invention.

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Brief description of the figures

Fig. 1. Shows the UV absorption spectra of bromides of ethylammonium methacrylates derived from anthracenyl, naphthyl, acetonephthyl and pyrenyl together with the spectrum of the methacrylate carrier of the benzothiazole group.

Fig. 2. Shows the results of the MTT test. *: Statistical analysis with respect to TMX (p <0.05). **: Analysis statistical regarding the HEMA / EEMA 80:20 material (p <0.05).

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Examples of realization Example 1 Synthesis of Monomers Synthesis of monomers belonging to the general formula (I)

The monomers of general formula (I) are prepared by an alkylation process of 2- (N, N-dimethylamino) ethyl methacrylate monomer (DMAEMA) or 2- (N, N-diethylamino) ethyl methacrylate monomer (DEAEMA) with the halide of the corresponding radical R2, under mild conditions. The preparation of the monomer when R 1 is a methyl radical and R 2 is an aryl radical is described in Lu et al. (cf. G. Lu, D, Wu, R. Fu., Reactive & Functional Polymers 67, 355-366, 2007). The preparation of the monomer when R 1 is a methyl radical and R 2 is a naphthyl or anthracenyl radical is described in European patent application EP0500321A1. The preparation of the monomer when R 1 is a methyl radical and R 2 is a ketoaryl radical is prepared as described in Sarker et al. (cf. AM Sarker, et al ., Macromolecules 32, 5203-5209, 1999). This process is extensible to the other monomers collected in Formula (I).

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Synthesis of 2- (N-benzyl, N, N-dimethyl ammonium) ethyl methacrylate bromide (hereinafter MON.BENCILO):

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5

It was synthesized as follows:

i) was dissolved to dissolve methacrylate of 2- (N, N-dimethylamino) ethyl (DMAEMA) in ether diethyl and triethylamine at 0 ° C temperature,

ii) under a nitrogen atmosphere, was added drop by drop a stoichiometric amount of benzyl bromide, to the solution of (i) and allowed to react for 16 hours at stirring room temperature, and

iii) was isolated by filtration obtaining a white powder that was washed with diethyl ether, dried under vacuum until heavy constate and was characterized by nuclear magnetic resonance of proton (1 H-NMR) and carbon (13 C-NMR). Quantitative performance

1 H-NMR (300 MHz, D 2 O, 45 ° C) δ (ppm): 7.84 (s, 5H, Ar ), 6.42 (s, 1H, COCH 3 = C Ha H), 6.04 (s, 1H, OCOCH_ {3} =
C Hb H), 4.96 (t, 2H, J = 4.4 Hz, N + C H 2 ), 4.87 (s, 2H, ArC H2 ), 4.05 (t, 2H, J = 4.4 Hz, CO 2 C H 2 ), 3.4 (s, 6H, N Me 2 ). 2.20 (s, 3H, OCOC H {3}).

13 C-NMR (75 MHz, D 2 O, 45 ° C) δ (ppm): 169.1, 135.9, 133.7, 131.6, 129.9, 128.4, 127.5, 70.0, 63.3, 59.0, 51.0, 17.9.

Theoretical refractive index, n_ {D} 20 = 1,517.

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Synthesis of 2- (N-methylenenaphthyl, N, N-dimethylammonium) ethyl methacrylate bromide (hereinafter MON.NAFTILO):

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6

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The synthesis of the MON.NAFTILO monomer comprises the following stages:

i) began to dissolve 2-bromomethylnaphthalene in hexane at temperature environment and,

ii) under a nitrogen atmosphere, was added drop by drop a solution of a stoichiometric amount of methacrylate 2- (N, N-dimethylamino) ethyl (DMAEMA) at solution of (i) for 10 min and allowed to react for 16 hours at room temperature under stirring, and

iii) a white powder was isolated by filtration that washed with hexane, dried under vacuum until constant weighing and characterized by proton and carbon nuclear magnetic resonance. Quantitative performance

1 H-NMR (300 MHz, D 2 O, 45 ° C) δ (ppm): 8.1-8.25 (m, 4H, Ar ), 7.83 (t, 2H, J = 3.7 Hz, Ar ), 7.72 (d, 1H, J = 8.4 Hz, Ar ), 6.35 (s, 1H, COCH 3 = C Ha H), 5.98 (s, 1 H, OCOCH 3 = C Hb H), 4.84 (s , 2H, N + C H 2 ), 4.80 (s, 2H, ArC H 2 ), 3.94 (t, 2H, J = 4.4 Hz, CO 2 C H 2 ), 3.32 (s, 6H, N Me_ {2}), 2.13 (s, 3H, OCOC H {3}).

13 C-NMR (75 MHz, D 2 O, 45 ° C) δ (ppm): 168.9, 135.7, 134.2, 134.1, 133.2, 129.5, 129.0, 128.7, 128.3, 127.8, 124.8, 69.9, 63.2, 58.9, 51.1, 17.9.

Theoretical refractive index, n_ {D} 20 = 1,577.

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Synthesis of 2- (N-methylenanthracenyl, N, N-dimethylammonium) ethyl methacrylate bromide (MON.ANTRAC):

7

includes the following stages:

i) was dissolved to dissolve methacrylate of 2- (N, N-dimethylamino) ethyl (DMAEMA) in dichloromethane at 0 ° C temperature,

ii) under a nitrogen atmosphere, was added drop by drop a solution of a stoichiometric amount of 2-bromomethylantracene at the solution of (i) during 5 min and allowed to react for 16 hours at room temperature in agitation, and

iii) a yellowish powder was isolated by filtration which was washed with diethyl ether, dried under vacuum until constant heavy and was characterized by nuclear magnetic resonance of proton and carbon. Yield 86%.

1 H-NMR (300 MHz, CDCl 3) δ (ppm): 8.82 (d, 2H, J = 9.0 Hz, Ar ), 8.43 (s, 1H, Ar ), 7.89 (d, 2H , J = 8.3 Hz, Ar ), 7.62 (t, 2H, J = 7.2 Hz, Ar ), 7.4 (dd, 2H, J = 6.7, 8.3 Hz, Ar ), 6.24 (s, 2H, ArC H2 ), 6.05 (s, 1H, COCH 3 = C Ha H), 5.52 (t, J = 1.27 Hz, 1H, OCOCH 3 = C Hb H), 4.67 (s, 4H, J = 2.3, N <+> C H 2 , CO 2 C H 2 ), 3.22 (s, 6H, N Me 2 ), 1.81 (s, 3H, OCOC H 3 ).

13 C-NMR (75 MHz, CDCl 3) δ (ppm): 166.2, 134.9, 133.1, 132.2, 131.0, 129.2, 128.3, 127.3, 125.3, 124.7, 117.5, 63.8, 61.1, 58.3, 50.8, 18.2.

Theoretical refractive index, n_ {D} 20 = 1,625.

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Synthesis of 2- (N-methylene pirenil, N, N-dimethylammonium) ethyl methacrylate bromide monomer (MON.PIRENI-
THE):

8

includes the following stages:

i) was dissolved to dissolve methacrylate of 2- (N, N-dimethylamino) ethyl (DMAEMA) in dichloromethane at 0 ° C temperature,

ii) under a nitrogen atmosphere, was added drop by drop a solution of a stoichiometric amount of 2-Bromomethylpyrene to the solution of (i) for 10 min and allowed to react for 16 hours at room temperature in agitation, and

iii) a yellowish powder was isolated by filtration which was washed with diethyl ether, dried under vacuum until constant heavy and was characterized by nuclear magnetic resonance of proton and carbon. Yield 89%.

1 H-NMR (300 MHz, CDCl 3) δ (ppm): 8.82 (d, 1H, J = 9.4 Hz, Ar ), 8.30 (d, 1H, J = 7.9 Hz, Ar ), 7.97-8.11 (m, 2H, Ar ), 7.83-7.93 (m, 3H, Ar ), 7.71 (d, 1H, J = 8.7 Hz, Ar ), 7.60 (m, 1H, Ar ), 6.05 (s, 2H , ArC H 2 ), 6.03 (s, 1H, COCH 3 = C Ha H), 5.50 (s, 1H, OCOCH 3 = C Hb H), 4.65 (s, 2H, N + } C H 2 ), 4.42 (s, 2H, CO 2 C H 2 ), 3.39 (s, 6H, N Me 2 ), 1.80 (s, 3H, OCOC H 3 ) .

13 C-NMR (75 MHz, CDCl 3) δ (ppm): 166.1, 135.4, 134.8, 134.2, 134.1, 132.6, 132.4, 131.8, 130.5, 130.3, 130.2, 129.9, 129.6, 128.8, 127.3, 126.6, 126.2, 126.0, 125.9, 124.2, 123.6, 123.3, 119.6, 66.0, 62.5, 58.1, 50.1, 18.1.

Theoretical refractive index, n_ {D} 20 = 1,693.

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Synthesis of 2- (N-acetophenyl, N, N-dimethylammonium) ethyl methacrylate bromide monomer (MON.ACETOFENI-
THE):

9

includes the following stages:

i) began to dissolve 2-Bromoacetophenone in hexane at temperature ambient,

ii) under a nitrogen atmosphere, was added drop by drop a stoichiometric amount of methacrylate of 2- (N, N-dimethylamino) ethyl (DMAEMA) at solution of (i) and allowed to react for 16 hours at stirring room temperature, and

iii) a white powder was isolated by filtration that washed with hexane, dried under vacuum until constant weighing and characterized by proton and carbon nuclear magnetic resonance. Quantitative performance

1 H-NMR (300 MHz, CDCl 3) δ (ppm): 8.01 (dd, 2H, J = 7.16, 1.32 Hz, Ar ), 7.56 (dt, 2H, J = 7.35, 1.18 Hz , Ar ), 7.41 (dt, 1H, J = 8.1, 1.36 Hz, Ar ), 5.87 (s, 2H, Ar CH2CO ), 5.83 (s, 1H, COCH3 = C Ha H), 5.35 (s, 1H, OCOCH 3 = C Hb H), 4.60 (t, 2H, J = 2.3, N + C H 2 ), 4.41 (t, 2H, J = 2.3 Hz, CO_ {2 C H 2 ), 3.72 (s, 6H, N Me 2 ), 1.71 (s, 3H, OCOC H 3 ).

13 C-NMR (75 MHz, CDCl 3) δ (ppm): 190.9, 166.1, 134.8, 134.7, 133.9, 128.9, 128.4, 127.0, 66.8, 62.5, 58.1, 53.0, 17.9.

Theoretical refractive index, n_ {D} 20 = 1,521.

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Synthesis of 2- (N- acetone- ethyl, N, N-dimethylammonium) ethyl methacrylate bromide monomer (MON.ACETONAF-
LINDEN):

10

includes the following stages:

i) began to dissolve 2- (bromoacetyl) naphthalene in hexane at room temperature,

ii) under a nitrogen atmosphere, was added drop by drop a stoichiometric amount of methacrylate of 2- (N, N-dimethylamino) ethyl (DMAEMA) at solution of (i) for 10 min and allowed to react for 16 hours at room temperature under stirring, and

iii) a white powder was isolated by filtration that washed with hexane, dried under vacuum until constant weighing and characterized by proton and carbon nuclear magnetic resonance. Quantitative performance

1 H-NMR (300 MHz, CDCl 3) δ (ppm): 8.84 (s, 1H, Ar ), 7.93 (d, 1H, J = 8.1 Hz, Ar ), 7.85 (dd, 1H , J = 1.37, 8.6 Hz, Ar ), 7.71 (d, 2H, J = 8.8 Hz, Ar ), 7.50 (dt, 1H, J = 1.1, 7.0 Hz, Ar ), 7.39 (dt, 1H, J = 1.1 , 7.0 Hz, Ar ), 6.0 (s, 2H, 2H, Ar CH2CO ), 5.79 (s, 1H, COCH3 = C Ha H), 5.25 (s, 1H, OCOCH_3 = C Hb H), 4.60 (t, 2H, J = 2.3, N + C H 2 ), 4.39 (t, 2H, J = 2.3 Hz, CO 2 C H 2 ), 3.73 (s, 6H, N Me_ {2}), 1.65 (s, 3H, OCOC H {3}).

13 C-NMR (75 MHz, CDCl 3) δ (ppm): 190.9, 166.1, 135.8, 134.6, 132.1, 131.5, 131.1, 130.0, 129.3, 128.6, 127.5, 127.0, 122.7, 66.8, 62.6, 58.1, 53.1, 17.9.

Theoretical refractive index, n_ {D} 20 = 1,577.

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Synthesis of monomers belonging to the general formula (IV)

The monomers of general formula (IV) are prepared by reacting methacryloyl chloride with the alcohol of the corresponding benzothiazolylthio alkyl in the presence of triethylamine, as described in US Pat. US7045558, for the monomer when n is equal to 2. This obtaining procedure is extensible to the rest of the monomers which are collected in Formula (IV).

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Synthesis of 2- (benzothiazolylthio) ethyl methacrylate (MON.BENZOT):

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eleven

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It was synthesized in two stages. The first stage comprises the following Steps:

i) began to dissolve 2-mercaptobenzothiazole (1 eq), KOH (1.5 eq) and Kl (0.5 eq) in a mixture water: ethanol 1: 1 at reflux

ii) to this mixture was added chloroethanol (1.5 eq) and allowed to react for 16 hours while maintaining reflux,

iii) a white powder was isolated by evaporation of ethanol, dichloromethane extraction and purification by silica gel chromatography with hexane: ethyl acetate (7: 3) which was identified as 2- (benzothiazolylthio) ethanol by resonance Proton and carbon nuclear magnetic. Yield 90%.

1 H-NMR (300 MHz, CDCl 3) δ (ppm): 7.87 (dt, 1H, J = 0.47, 8.1 Hz, Ar ), 7.76 (dt, 1H, J = 0.56, 7.9 Hz , Ar ), 7.44 (dt, 1H, J = 1.27, 7.35 Hz, Ar ), 7.33 (dt, 1H, J = 0.56, 7.35 Hz, Ar ), 4.21 (s, 1H, O H ), 4.09 (t, 2 H, J = 4.8 Hz, C H 2 OH), 3.54 (t, 2H, J = 5.27 Hz, C H 2 S).

13 C-NMR (75 MHz, CDCl 3) δ (ppm): 167.8, 153, 135.8, 126.7, 125, 121.8, 121.5, 63, 37.

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The second stage consisted of obtaining the methacrylic ester and includes the following steps:

i) began to dissolve 2- (benzothiazolylthio) ethanol with Et 3 N in dichloromethane at 0 ° C,

ii) under a nitrogen atmosphere, was added drop by drop a stoichiometric amount of methacryloyl chloride to the solution of (i) for 30 min and allowed to react for 3 hours at 0 ° C stirring temperature, and

iii) a clear oil was isolated by extraction with dichloromethane and was identified as methacrylate 2- (benzothiazolylthio) ethyl by nuclear magnetic resonance of proton and carbon Yield 85%.

1 H-NMR (300 MHz, CDCl 3) δ (ppm): 7.85 (d, 1H, J = 8.1 Hz, Ar ), 7.73 (d, 1H, J = 7.9 Hz, Ar ), 7.40 (dt, 1H, J = 1.17, 7.30 Hz, Ar ), 7.28 (dt, 1H, J = 1.08, 7.44 Hz, Ar ), 6.11 (s, 1H, COCH 3 = C Ha H), 5.54 ( q, 1H, J = 1.51 Hz, OCOCH 3 = C Hb H), 4.53 (t, 2H, J = 6.40 Hz, C H 2 CO 2), 3.66 (t, 2H, J = 6.40 Hz, SC H 2 ), 1.92 (t, 3H, J = 1.04 Hz, OCOC H 3 ).

13 C-NMR (75 MHz, CDCl 3) δ (ppm): 166.9, 165.4, 152.9, 135.8, 135.2, 126.0, 129.5, 124.2, 121.5, 120.9, 62.7, 31.7, 18.1.

Theoretical refractive index, n_ {D} 20 = 1,623.

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Example 2 Determination of UV absorption of synthesized monomers in Example 1

All UV spectra are recorded in dichloromethane (10-4M) on a Perkin Elmer UV / VIS spectrometer Spectrometer Lambda 16. It is obtained that anthracenyl monomers and naphthyl absorb UV light in the range between 220 and 300 nm and the acetone-ethyl and benzothiazole monomers in the range between 220 and 320 nm, which means that these four monomers can act as UV-B light filters. The pyrene monomer presents absorption in the range between 220 and 380 nm, covering the entire UV-A light range considered as harmful to the retina, so that this monomer acts as UV light filter If this monomer is incorporated into the formulation of IOL in the proper amount would avoid having to use additional UV absorption agents. The UV spectra of the cited monomers are shown in figure 1.

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Example 3 Copolymer systems for flexible IOLs containing bromide methacrylate 2- (N-benzyl, N, N-dimethylammonium) ethyl

Copolymeric systems were prepared based on 2-hydroxyethyl methacrylate (HEMA), of formula:

12

and methacrylate bromide from 2- (N-benzyl, N, N-dimethylammonium) ethyl (MON.BENCILO) in the presence of one or more voluminosote monomers formula (III) such how:

- 2-ethoxyethyl methacrylate (EEMA), of formula:

13

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- 2-phenoxyethyl methacrylate (FEMA), of formula:

14

- and benzyl methacrylate (BMA), of formula:

fifteen

from the compositions in the power indicated in Table I. The disks are obtained by copolymerization reaction of the monomers in bulk. Be poured the corresponding monomer mixtures into molds polypropylene cylinders and 0.3% -p of azobisisobutyronitrile (AIBN) as radical initiator. The reaction medium with nitrogen and the mold was closed with a plug. It was then heated at 70 ° C for 16 h. Once this is finished time the samples that were subjected to a post-cure at 70 ° C for 24 h. Finally, the discs were dried under vacuum until constant heavy. With this procedure 14.5 mm copolymer discs of diameter and thicknesses between 0.5 and 4 mm depending on the reaction volume used.

TABLE I System feed compositions synthesized

16

The degree of hydration of these systems is determined using a borate buffer solution of pH = 7.3 whose composition is shown in Table II.

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TABLE II Borate buffer composition of pH = 7.3

17

Three samples of each of the different systems prepared in the buffer solution and incubated at 37 ° C to simulate physiological conditions. The sample at different times, its surface was dried carefully with filter paper and weighed to a constant weight. TO that time the percentage of the degree of hydration is calculated (H) by the following equation.

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18

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where P H is the weight of the hydrated sample once equilibrium is reached; P_ {S} is the initial weight of the dry sample.

The refractive index of these materials is determined with an ABBE refractometer (ZEISS 133988) at a length of 589 nm wave using a sodium lamp, both in the dry samples as in hydrated samples once reached balance. The measurements were made at 20 ° C (n_ {20}).

The flexibility of the systems was studied by determining the transition temperature measurement vitreous (T g) of the copolymers in the dry state. These measures are performed on a differential scanning calorimeter (Perkin Elmer DSC7 connected to a TAC 7 / DX analyzer). To do this, they deposited 15 mg of the dried sample inside an aluminum capsule sealed and heated at a constant speed of 10ºC / min with a flow of N2 of 50 ml / min in the temperature range of -10 to 200 ° C The temperature calibration of the device was carried out with indium and zinc patterns. Glass transition temperature (T_ {g}) was taken as the midpoint of the transition of the heat capacity observed on the thermogram corresponding to second sweep At least two samples from each were analyzed composition.

The percentage values of the degree of hydration are shown in Table III along with the values of the refractive indices taken from the dry and hydrated sample and from glass transition temperatures.

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TABLE III Values of degree of hydration (H), index of refraction (n_ {20}) and glass transition temperature (T g) of the copolymers obtained with the feeds of the Table I

19

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The surface wettability characteristics of the materials were evaluated by contact angle measurements on a G10 goniometer (KRÜS) and using the resting drop method (Sessile Drop). For this purpose, the contact angle of a polar liquid (distilled water, γL = 72.8 mJ / m2) and a nonpolar liquid (diiodomethane, γL = 51.8 mJ /) were taken m2) applying between 8-10 drops of 5 µl of each liquid on the surface of each sample. The surface tension was determined using the Owens method (cf. DK Owens, RC Wendt. J Appl Polym Sci 13, 1741-1747, 1969).

TABLE IV Values of contact angles in water (\ theta H 2 O) and diiodomethane (2 CH 2 I 2), and energy surface of the solid (γ S) with its polar components (γ S) and dispersive (γ S), for the copolymers containing the MON.BENCILO monomer

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twenty-one

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Example 4 Copolymer systems for flexible IOLs containing bromide of methacrylate 2- (N-methylenenaphthyl, N, N-dimethylammonium) ethyl and 2- (benzothiazolylthio) ethyl methacrylate

Copolymeric systems based on 2-hydroxyethyl methacrylate (HEMA), 2- (N-methylene naphthyl, N, N-dimethylammonium) ethyl (MON.NAFTILO) methacrylate and 2- (benzothiazolylthio) ethyl methacrylate (MON .WELL-
ZOT), in the presence of one or more monomers of formula (III) such as 2-ethoxyethyl methacrylate (EEMA), 2-phenoxyethyl methacrylate (FEMA) or benzyl methacrylate (BMA), from the compositions in the power shown in Table V.

TABLE V System feed compositions synthesized

2. 3

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The copolymerization and purification reaction of the materials obtained were made as described in the Example 3. Similarly, the determinations of the degree of hydration, refractive index of dry and hydrated materials, glass transition temperature as well as its properties superficial, were performed according to the protocols described in the Example 3. The results obtained are shown in Tables VI and VII.

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TABLE VI Values of degree of hydration (H), index of refraction (n_ {20}) and glass transition temperature (T_ {g}) of the systems obtained with the feeds of the Table V

24

TABLE VII Contact angles in water (H H 2 O) and diiodomethane (CH CH 2 I 2) and energy values surface of the solid (γ S) with its components polar (γ S) and dispersive (γ S), of the systems that contain the monomer MON.NAFTILO

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25

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Example 5 Copolymer systems for flexible IOLs containing bromide of methacrylate 2- (N-acetophenyl, N, N-dimethylammonium) ethyl, methacrylate bromide 2- (N-acetonaphthyl, N, N-dimethylammonium) ethyl and 2- (benzothiazolylthio) ethyl methacrylate

Copolymeric systems were prepared based on 2-hydroxyethyl methacrylate (HEMA) in the presence of one or more of the monomers, methacrylate bromide 2- (N-acetophenyl, N, N-dimethylammonium) ethyl (MON.ACETOFENILO), methacrylate bromide 2- (N-acetonaphthyl, N, N-dimethylammonium) ethyl (MON.ACETONAFTILO) and 2- (benzothiazolylthio) ethyl methacrylate (MON.BENZOT), and of one or more monomers of formula (III) such such as 2-ethoxyethyl methacrylate (EEMA) or 2-phenoxyethyl methacrylate (FEMA). The compositions in the feed of the prepared systems are indicated in Table VIII.

TABLE VIII System feed compositions synthesized copolymers

27

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The copolymerization and purification reaction of the materials obtained was performed as described in the Example 3. Equally the determinations of the degree of hydration as well as the index of refraction of materials in the dry state and hydrated were carried out according to the protocols described in the Example 3. The results obtained are shown in Table IX.

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TABLE IX Values of degree of hydration (H) and index of refraction (n_ {20}) of the systems obtained with the Table VIII feeds

28

29

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Example 6 Bactericidal activity of monomers synthesized in the Example 1

The bactericidal activity of the monomers was determined by the Agar Diffusion Method described by Brauer et al. (cf. AW Bauer, WM Kirby, JC Sherris, M. Turck. Am J Clin Pathol 45, 493-496, 1966) using two different trials. The Staphylococcus epidermidis (RA 231) and Pseudomonas aeruginosa (B6) strains were used as a model culture. The culture was preserved by storing at -80 ° C in glycerin / water mixtures (20% v / v). Solutions of each monomer were prepared in 2M concentration in water for n-alkylammonium methacrylate bromides and in DMSO for benzothiazole methacrylate. Water and DMSO were used as targets of bactericidal activity. The culture medium that was heart and brain broth, BHI, (Laboratorios Difco, USA). All experiments were performed in triplicate.

First, the culture was proceeded in 5 ml of BHI medium for a whole night at 37 ° C, thus obtaining a stationary culture After that time, using a colorimeter (Boecos-22 Spectrophotometer, Germany) the absorbance of stationary culture at 600 nm. To adjust the value from the number of viable bacteria the number of units is determined suspension colony forming (UCF) with different optical densities, using standardized counting techniques on half-agar plates. To determine the number of UCF 1/10, 1/100 and 1/1000 dilutions of the cultures were prepared stationary Approximately 1.5 ml of them were taken and added over a hot mixture of medium of agar culture (2%) previously sterilized in autoclave. Before the mixture solidifies, each mixture of medium of culture-agar spread on three Petri dishes and they were always solidified inside a cabin of laminar flow to avoid contamination.

For the plate-well test , agar plates with culture medium containing a concentration of the bacterial strain of 1.5 x 10 8 suspension colony forming units (UCF) were first prepared. 1.5 ml aliquots of the cell culture were mixed with 150 ml of the corresponding sterilized and molten medium, distributed in Petri dishes and allowed to solidify at room temperature. 6 wells were drilled in each plate which were filled with 40 µl of the monomer solutions. All plates were incubated at 37 ° C for 24 and 48 h. For the antibiogram assay agar plates were prepared with BHI culture medium as described above, but without the addition of the bacterial strain. When the plates were cold and the hardened agar was spread on the surface of different plates for each crop, with the help of a sterile spatula, 1/10 dilutions of the previously prepared cultures. Subsequently, 6 special disks for antibiograms (Schleicher & Schüll), soaked with the solutions to be tested, were deposited on the surface. After this, the plates were closed and grown for 24 and 48 h at 37 ° C. The inhibitory activity of each compound was determined based on the presence of inhibition halo in the vicinity of the wells or discs that indicate the absence of colony formation. The results of this experiment are expressed as mean diameter of the halo in millimeters. The size of the halos measured at 24 h for the different monomers including the 4 mm of the well and the 9 mm of the discs, are collected in Table X. At 48 h of incubation the same results are obtained. It can be seen that all monomers have antimicrobial activity against S. epidermidis and P. aeruginosa , however the monomers of n-alkylammonium methacrylate bromides have a markedly higher activity than the monol carrier monomer. Within n-alkylammonium methacrylate bromides, naphthyl and acetophenyl derivatives have a slightly higher activity against P. aeruginosa compared to that of benzyl monomer. In addition, a good correlation is observed in the results obtained in both types of trials. In the plate-well test, n-alkylammonium methacrylate bromides produce double inhibition halo.

TABLE X Halos of inhibition at 24 h for monomers derived from benzyl, naphthyl and acetophenyl and benzothiazole obtained by the Agar Diffusion Method

30

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Example 6 Biocompatibility of copolymer systems

The cytotoxicity from any extract of the materials was analyzed by cell cultures using the MTT assay. For this test, human fibroblasts (FBH) grown at 37 ° C were used. The culture medium was Dulbecco's Modified Eagle's Medium Eagle (MEM) modified with HEPES and enriched with 10% fetal bovine serum (FBS), 200 mM L-glutamine, 100 units / ml penicillin and 100 µg / ml streptomycin . The culture medium was changed at selected time intervals. As a negative control of the test, Thermanox® (TMX) is used, a 1% v / v solution of Triton X-100 (TRITON) is used as a positive control of the test and HEMA disks are tested as a control of the materials developed for IOLs -EEMA 80:20, which is the composition of the commercial lens of AJL Ophthalmics. The ratio of materials tested is shown in Table XI.

TABLE XI Composition of the materials used in the test biocompatibility

31

10 mm diameter and 1 mm thick discs of the materials to be tested and Thermanox® (TMX) were submerged in 5 ml of MEM. They were then placed in an oven at 37 ° C, He extracted the medium at different times (6 h, 1, 2, 3 and 7 days) and replaced with another 5 ml of fresh medium. All extracts are obtained under sterile conditions. The fibroblasts were seeded at a density of 8 x 10 4 cells / ml in complete medium in a 96-well sterile culture plate and incubated at confluence. Then, the medium was replaced with the corresponding eluted extracts from the samples, with exudates of TMX and by a 1% v / v solution of triton X-100 in culture medium. The plates were incubated at 37 ° C in a humidified air atmosphere with 5% CO2 for 24 hours. A solution of MTT, 5 mg / ml in a solution was prepared of phosphate buffer (PBS) tempered and filtered before use, obtaining the mother solution. This, in turn, was diluted to 10% in fresh medium, obtaining the working solution. They were added 100 µl of this solution to each of the wells to give a final concentration of 0.5 mg / ml, and the plates were incubated at 37 ° C for 4 h. The contents of the wells were extracted and added 100 µL of dimethylsulfoxide (DMSO) to all wells in order to dissolve the MTT taken by the cells. after one 20s stirring at high intensity, absorbance was measured with a Biotek ELX808IU plate reader using a wavelength of 570 nm test and a reference wavelength of 630 nm. The results were normalized with respect to Thermanox® (TMX = 100%) and the statistical study of the analysis of variance was carried out (ANOVA) of them with respect to the TMX and with respect to the material HEMA-EEMA (p <0.05). The test results are shown in Figure 2. It can be seen that leachate from All materials for IOLs do not produce toxic effects on the medium, allowing the cell viability of the cultures made in your presence reach values close to 100% in all the cases.

Claims (29)

1. Polymeric composition comprising at least a monomer of general formula (I) and at least one acrylic monomer hydrophilic, 33

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where:

n is a value of 1 to 12;

X is an anion which is selected from the group comprising a halogen or a sulfonate,

R_ {1} is a hydrogen or a methyl group;

R2 and R 3 are the same or different from each other, and represent a radical (C 1 -C 3) alkyl.

R_ {4} is a aryl radical, substituted or unsubstituted, or an acetyl radical, substituted or unsubstituted.

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2. Composition according to claim 1, wherein n is a value from 2 to 6. 3. Composition according to any of the claims 1 or 2, wherein R1 is a methyl. 4. Composition according to any of the claims 1 to 3, wherein R 2 and / or R 3 is a methyl or a ethyl. 5. Composition according to any of the claims 1 to 4, wherein R 4 is selected from the list that it comprises phenyl, naphthyl, anthracenyl, pyrenyl, acetoaryl, acetonaphthyl, acetoantracenyl, acetopirenyl or acetocoumarin. 6. Composition according to any of the claims 1 to 5, wherein the monomers of formula (I) are selected from the list comprising methacrylate bromide of 2- (N-benzyl, N, N-dimethylammonium) ethyl, methacrylate 2- (N-methylenenaphthyl, N, N-dimethylammonium) ethyl, methacrylate 2- (N-methylene pirenyl, N, N-dimethylammonium) ethyl, methacrylate 2- (N-Methylenacetophenyl, N, N-dimethylammonium) ethyl, methacrylate 2- (N-Methylenaketonephthyl, N, N-dimethylammonium) ethyl or any of its combinations. 7. Composition according to any of the claims 1 to 6, wherein the hydrophilic acrylic monomer is of general formula (II): 3. 4

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where:

n is from 0 to 4,

m is from 0 to 1; Y

R_ {1} is a hydrogen or a methyl group.

8. Composition according to claim 7, wherein n is 2 and / or m is 0. 9. Composition according to any of the claims 7 or 8, wherein R1 is methyl. 10. Composition according to any of the claims 7 to 9, wherein the monomer of formula (II) is the 2-hydroxyethyl methacrylate (HEMA). 11. Composition according to any of the claims 1 to 10, further comprising at least one monomer of general formula (III),

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35 where:

n is 1 or 2,

R_ {1} is a hydrogen or a methyl group; Y

R2 is select from the list comprising a hydrogen, an alkyl (C 1 -C 6) or an alkoxy or an aryl.

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12. Composition according to claim 11, where R1 is a methyl. 13. Composition according to any of the claims 11 or 12, wherein R2 is a group that is selected from the list comprising methyl, methoxy, ethyl, ethoxy, propyl, propoxy, butyl, butoxy, phenyl, phenoxy, naphthyl or naphthyloxy. 14. Composition according to any of the claims 11 to 13, wherein the monomer of formula (III) is the 2-ethoxyethyl methacrylate, benzyl methacrylate, 2-phenoxyethyl methacrylate or any of its combinations 15. Composition according to any of the claims 1 to 14, further comprising at least one monomer of general formula (IV),

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36

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where:

n is from 1 to 6.

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16. Composition according to claim 15, where the monomer of formula (II) is methacrylate of (benzothiazolylthio) ethyl. 17. Composition according to any of the claims 1 to 16, further comprising an absorption agent UV 18. Composition according to claim 17, where the UV absorbing agent is a compound that contains benzophenones or benzotriazoles. 19. Procedure for obtaining a composition according to claims 1 to 18, comprising the following stages:

i)

the monomers of general formula (I) are mixed with the monomers of general formula (II) in the presence of an initiator of radical polymerization,

ii)

the reaction mixture of the step is deoxygenated (i),

iii)

The mixture obtained in step (ii) is subjected to heat treatment at a temperature between 45ºC and 70ºC, during the time necessary to reach the total conversion,

iv)

subsequently the material of step (iii) is submitted at a post-cure at a temperature between 60 ° C and 80 ° C for a time between 24 and 96 h.

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20. Method according to claim 19, in which in step (i) monomers of general formula (III) is added and / or general formula (IV). 21. Procedure according to any of the claims 19 or 20, wherein in step (i) a UV absorption agent. 22. Procedure according to any of the claims 19 to 21, wherein the components that are mixed in (i) are monomers that belong to the general formula (I) in a amount between 1-30% by weight, monomers belonging to the general formula (II) in an amount between 40-60% by weight and / or monomers which belong to formula (III) in an amount between 5-20% by weight of the final composition. 23. Method according to claim 22, where the components that are mixed in (i) also comprise monomers belonging to the general formula (IV) in an amount comprised between 1-30% by weight of the composition final. 24. Procedure according to any of the claims 22 or 23, wherein the components that are mixed in (i) also comprises at least one UV absorbing agent in a proportion of between 0.1-5% by weight with respect to the final composition 25. Procedure according to any of the claims 19 to 24, wherein the polymerization initiator radical is azobisisobutyronitrile, AIBN, in a proportion between 0.3 and 2% by weight of the composition. 26. Procedure according to any of the claims 19 to 25, wherein in step (ii) the mixture of reaction is deoxygenated with nitrogen stream. 27. Procedure according to any of the claims 19 to 26 wherein in step (iii) the treatment Thermal is 50-70ºC for 16-24 hours. 28. Procedure according to any of the claims 19 to 27, wherein the post cure step (iv) of the samples is performed at a temperature between 60-80 ° C for a time of 24 h. 29. Use of the composition according to any of claims 1 to 18, for the manufacture of flexible lenses intraocular