WO1999029750A1

WO1999029750A1 - Method for making a transparent polymer material resistant to protein deposit, material obtained by said method, contact lenses and intraocular implants made of said material

Info

Publication number: WO1999029750A1
Application number: PCT/FR1998/002610
Authority: WO
Inventors: Isabelle Calderara; Corinne Grollier
Original assignee: Essilor International Compagnie Generale D'optique
Priority date: 1997-12-05
Filing date: 1998-12-03
Publication date: 1999-06-17
Also published as: FR2772033A1; JP2001525464A; EP1036102A1; NO20002840D0; NO20002840L

Abstract

The invention concerns a method for making a transparent polymer material with little tendency to accumulate deposit. The method consists in immersing a transparent polymer matrix in a solution in a solvent for swelling the polymer matrix of a composition comprising a zwitterion polymerizable monomer and an agent for cross-linking the monomer to cause the polymer matrix to swell and become impregnated with the composition, optionally removing the matrix from the solution and hardening the composition impregnated within the matrix, said hardening being carried out in the presence of a polymerization initiator initially present in the matrix or the swelling solution. The invention is useful for making contact lenses and intraocular implants.

Description

Method for manufacturing a transparent polymer material resistant to protein deposition, material obtained by this method, contact lenses and intraocular implants made of this material.

The invention relates generally to a method of manufacturing transparent, preferably hydrophilic, polymeric materials resistant to fouling by proteins, as well as the materials obtained by this method, contact lenses and intraocular implants. made from these materials.

It is known that contact lenses, when they are in the presence of the tear medium of the wearer's eye, exhibit a tendency to accumulate on their surfaces deposits due to the species present in this tear medium, such as proteins, lipids, etc. Such deposits thus formed on the surface of the lens greatly reduce visual acuity and the wearer's comfort. In some extreme cases, in the absence of lens maintenance, an inflammatory and immune reaction of the eye to protein deposits occurs and can cause giant papillary conjunctivitis. Furthermore, in the case of hydrophilic soft lenses, their disinfection by boiling still denatures the protein materials, which coagulate, which leads to the formation of white and opaque deposits.

It is therefore desirable to be able to have materials for contact lenses, which, by their nature, have a low tendency to accumulate deposits, in particular proteinaceous materials.

The documents EP-A-555,295 and EP-A-563,293 describe inter alia crosslinked polymers obtained by copolymerization of a zwitterionic monomer and a neutral diluent monomer. Contact lenses made from such copolymers have reduced fouling. The document WO 94/14897 describes mixtures of polymers comprising:

(A) a polymer carrying pendant zwitterionic groups, and (B) a polymer having the desirable mechanical and / or physical properties.

These materials are especially suitable for biomedical applications for the manufacture of articles coming into contact with blood, plasma, serum and / or a film of tears. In practice, in document WO 94/14897, the mixture of polymers is obtained by first preparing the polymer (A) and subsequently mixing it with the polymer (B).

When the polymer (B) is a thermosetting polymer, the simple techniques of mixing polymers are no longer applicable, and in this case it is then necessary to include the polymer (A) in admixture with monomers of the polymer (B) or a prepolymer of the polymer (B) before the final stage of formation of the crosslinked network.

Furthermore, document WO 94/14897 specifies that during the preparation of the polymer (A), when comonomers capable of producing crosslinking are present, the polymerization conditions are established so that crosslinking does not occur during the polymerization. Thus, for example, actinic radiation would not be used to prepare a polymer containing a monomer which can crosslink by exposure to such actinic radiation. The present invention therefore relates to a process for manufacturing a transparent polymer material having a low tendency to accumulate deposits and in particular such a process using actinic radiation.

The method of manufacturing a transparent polymer material having a low tendency to accumulate deposits according to the invention, comprises: a) immersing a transparent polymer matrix in a solution comprising a swelling solvent for the polymer matrix and a curable composition, the curable composition comprising: - a polymerizable monomer comprising at least one zwitterionic grouping; and

- a monomer crosslinking agent, for swelling the polymer matrix and impregnating it with said composition; b) optionally removing the polymer matrix, swollen and impregnated with said composition, from the solution; and c) the curing of said composition within the polymer matrix, this curing taking place in the presence of a polymerization initiator initially present in the matrix or the swelling solution. The invention also relates to a transparent polymer material having a low tendency to deposit build-up which comprises a transparent polymer matrix and an interpenetrating network of a polymer comprising zwitterionic groups, the interpenetrating network of the polymer comprising zwitterionic groups being obtained by the above method, as well as contact lenses and intraocular implants made of this transparent polymer material.

The transparent polymer matrices useful in the process of the present invention are all transparent polymer matrices formed by the polymer materials usually used for the manufacture of contact lenses and intraocular implants, in particular hydrophilic polymer materials and very particularly hydrophilic polymer materials of hydrogel type, generally previously shaped.

However, it is also possible in the context of the invention to use hydrophobic polymer matrices, in particular silicone

(polydiorgano siloxanes), for example polydimethylsiloxanes.

Obviously the polymeric material can consist of a mixture of these polymers and copolymers.

These polymeric materials are well known in the art and include among the polymers useful in the process of the present invention, polymers and copolymers based on (meth) acrylate, in particular C _j -C such as methyl (meth) acrylate, hydroxy (alkyl) (meth) acrylates, in particular of CC ₄ alkyl such as hydroxyethylmethacrylate (HEMA) and hydroxypropyl methacrylate (HPMA), polyhydroxy (alkyl ) (meth) acrylates such as polyhydroxyethylmethacrylates, N-vinyl lactams such as N-vinylpyrrolidone, vinyl monomers such as styrene, (alkylene glycol) (meth) acrylates such as ethylene glycol mono- or dimethacrylate and propylene glycol mono- or dimethacrylate, poly (alkylene glycol) (meth) alkoxylated acrylates such as poly (ethylene or propylene glycol) (meth) acrylates ethoxylated or propoxylated.

The silicone matrices which can be used are described in particular in patent EP 643,083 in the name of Essilor International.

Polymethylsiloxane (PDMS) matrices can be used in particular, prepared by hydrosilylation from siloxane prepolymers developed by the company Rhône-Poulenc under the reference RTV 70 141 A and B (silbione®).

Oil A consists of mono and divinyl polydimethylsiloxanes and a platinum catalyst. This part contains approximately 3.10 x 10 ⁴ vinyl functions per gram of RTV 70 141 A.

Oil B is a hydrogen methyl polydimethylsiloxane and contains approximately 4.07 x 10 ' ³ hydrogen silane functions per gram of RTV 70 141 B. The polymer matrices are obtained by mixing 10 parts of A and 1 part of B which are degassed and poured into polypropylene molds and then heated to obtain the molded product.

Preferably, in the process of the present invention, the transparent polymeric matrices are the hydrophilic or hydrophobic matrices which are preformed, in particular for the manufacture of contact lenses and intraocular implants.

The polymerizable zwitterionic monomers useful in the process of the present invention are any polymerizable monomer containing at least one zwitterionic group such as the zwitterionic monomers described in documents WO 94/14897, EP-A-555,295 and EP-A-563,293 .

Among the useful polymerizable zwitterionic monomers, those comprising ethylenic unsaturation are recommended.

Among these ethylenically unsaturated zwitterionic monomers, mention may be made of N- (3-sulfopropyl) -methacroyloxyethyl-N, N-dimethyl- ammonium-betaine (SPE), N- (3-sulfopropyl) -N-methacrylamido-propyl-N, N-dimethylammonium-betaine (SPP), l- (3-sulfopropyl) -2- vinyl-pyridinium-betaine ( SPV), N-methacryloyloxyethyl-N, N- dimethyl-N, 2-ethylcarboxy-betaine, N- (3-carboxypropyl) -N-methyl- aminoethylmethacrylate, N- (3-carboxypropyl) -N-methylamino- methacryloyloxyethyl-N, N-dimethylammonium-betaine (CPE), N- (3-carboxypropyl) aminoethylmethacrylate, and 2- (methacryloyloxy) ethyl- 2- (trimethylammonium) ethylphosphate.

The preferred polymerizable zwitterionic monomers are the sulfobetaines, and in particular the following compounds:

H ₂ C = CH ₂ - CH ₂ - SO ₃ ^υ (SPE)

(SPP); and

The concentration of polymerizable zwitterionic monomers in the impregnation solution according to the invention is generally between 5 and 95% by weight relative to the total weight of the solution, preferably between 25 and 75% by weight, and better still between 40 and 60% by weight.

Any conventional crosslinking agent can be used in the impregnating solutions of the invention. These agents are generally bifunctional compounds and in particular di (meth) acrylate compounds. The crosslinking agents recommended in the process of the present invention are poly (oxyalkylene) dimethacrylates, in particular poly (oxyethylene) dimethacrylates.

In general, the concentration of crosslinking agents in the impregnating solutions of the process of the invention is between 0.1 and 5% by weight relative to the total weight of the impregnating solution.

The initiators or initiators of polymerization of the impregnation solution according to the invention can be initiators of thermal polymerization or of photopolymerization or else a mixture of these two types of initiators of polymerization.

The thermal polymerization initiators or initiators used in the impregnation solutions according to the invention are generally peroxides or azo compounds such as benzoyl peroxide, 2,2'-azobis (2-methylpropionitrile) or methyl ether of benzoyl.

Preferably, the impregnation solutions of the process of the invention comprise a photo-initiator. These photo-initiators are all compounds producing free radicals under irradiation, either by itself or by cooperation with another proton-donating compound. That is to say that the photo-initiators used, or photopolymerization initiators, can be as well of photocleavable type as of photo-activatable type, with however a preference for those which are active to initiate the photopolymerization of the monomer for irradiation wavelengths in the visible or near UV range.

A photocleavable photoinitiator (or photoinitiator) comprises one or more compounds which function by directly generating one or more free radicals which initiate polymerization, while a photoclivable photoinitiator is formed of a system producing such radicals by a photoassisted redox reaction between a light absorbing compound and a hydrogen or electron donor, both present in the system. It is of course also possible to use mixtures of two types of photoinitiators. Examples of photocleavable compounds known per se are chosen from alkoxyacetophenone derivatives, benzoin ether, phosphine-oxides, benzoyloxime derivatives.

Examples of known photoactivatable photoinitiators include a free radical-producing absorber chosen from benzophenones, benzyles, xanthones, anthrones, thioxanthones, fluorenones, suberones, acridones, in association with, as a proton donor, an ethers compound, alcohols, amines, amino acids, or organometallic compounds. One can in particular use photoinitiators constituted by xanthones carrying an ionic radical such as those of the family described in the American patent US-A-4,791

213, the maximum absorption of which lies in the range from 390 to 405 nm.

In practice, the preferred photo-initiators used in the implementation of the process of the invention are chosen from thioxanthones and benzophenones carrying an alkyl amine or oxyalkylamine radical, in the form of an amine salt.

The concentration of photo-initiators in the impregnation solution is advantageously between 10 ^"5 M and 0.5 M, and in particular of the order of 10 ^{" 4} to 10 ^"2 M, in particular when it is a question of water soluble thioxanthones.

In combination, advantageously used as electron donors, an ethanolamine such as dimethyldiethanolamine

(MDEA) or triethanolamine (TEA), in a concentration of the order of 10 ^"2

M, preferably between 1.10 ^"2 and 5.10 ^{" 2} M. In another embodiment of the invention, the photoinitiators can be fixed photoinitiators, in particular in the case of silicone-based polymeric materials, such as described in international application PCT / FR 97/01147.

More particularly, the polymer matrix can be formed from a material based on crosslinked silicone polymer, that is to say one whose polymer network is three-dimensional, and whose characteristic is to include photoinitiator groups dispersed and fixed within of the silicone matrix.

In this embodiment, the crosslinked silicone matrix comprises photoinitiator groups or fragments distributed in a manner homogeneous in all its volume and up to the very heart of the matrix.

The photoinitiator groups can be fixed by the following techniques:

According to a first technique, the photoinitiator groups are fixed to the silicone matrix by a covalent chemical bond.

To this end, a photoinitiator is prepared functionalized by a silyl group SiH or by an unsaturated C = C double bond.

This double bond can be of vinyl, (meth) acrylic or allylic type. The photoinitiator compound is introduced into a crosslinkable liquid composition comprising:

. an oil A of a polysiloxane monomer or oligomer carrying Si-Vinyl groups;

. an oil B of a polysiloxane monomer or oligomer carrying Si-H groups;

. a metal catalyst for the hydrosilylation reaction.

During crosslinking carried out thermally, by hydrosilylation reaction, the photoinitiator compound is grafted onto the polysiloxane network via a covalent Si-C bond. According to a second fixing technique, a long-chain photoinitiator compound is used. This chain is preferably a polysiloxane chain on which the photoinitiator group (s) is (are) grafted. This photoinitiator compound is, in the same way as in the previous technique, introduced into the liquid mixture of polysiloxane precursors.

During the crosslinking of the mixture, the polysiloxane chain of the photoinitiator compound is physically immobilized within the crosslinked silicone polymer matrix obtained.

In this case, unlike the previous technique, there is no chemical bond between the photoinitiator compound and the silicone matrix, but a simple physical retention, due in particular to the three-dimensional character of the network of the crosslinked silicone polymer of the matrix.

However, whatever the fixing technique used, the photoinitiator groups remain fixed in the matrix of polysiloxane even when it is subjected to solvent extraction treatments. In other words, it is not possible to separate, by extraction with solvents, the photoinitiator groups from the matrix, whether these are grafted to the polymer forming the matrix or simply carried by a long chain compound physically immobilized at the within the matrix.

Thus, at the end of the hydrosilylation reaction, a material based on crosslinked silicone polymer is obtained comprising a matrix of crosslinked silicone polymer in which are distributed photoinitiator groups capable of generating free radicals by light irradiation.

The liquid silicone compositions used to obtain the silicone polymer matrix are preferably two-component polydimethylsiloxane oils, the essential constituent units of which are shown below:

Constituent A -

CH ₃ ÇH ₃

Constituent B - (Si -

CH ₃ H

These silicone oils are crosslinked using a hydrosilylation catalyst. Such catalysts are well known to those skilled in the art.

These are, for example, platinum, hexachloroplatmic acid, platinum-hydrocarbon complexes, and rhodium complexes.

Platinum-based catalysts are generally used at concentrations from 10 ppm to 500 ppm, preferably from 50 to 300 ppm. Reaction temperatures vary from room temperature to 250 ° C depending on the concentration and the type of catalyst used. Preferential temperatures vary from 50 ° C to 150 ° C.

Constituents A and B are used in proportions such that their mixture contains from 0.8 to 1.9 SiH bonds per 1 Si- bond.

Vinyl.

Preferably, the polydimethylsiloxane polymer (PDMS) is prepared by mixing two siloxane prepolymers developed by Rhône-Poulenc under the reference RTV70 141 A and B (silbione®) and the photoinitiator functionalized in the desired proportions.

Oil A consists of mono- and divinyl PDMS and a platinum catalyst. This part contains approximately 3, 10 x 10 ^{~ 4} vinyl functions per gram of RTV70 141 A and its number average molecular mass is 31200. Oil B is preferably a hydrogenomethyl PDMS and contains 4.07 x 10 ^"3 SiH functions per gram of RTV70 141 B and its number average molecular weight is 1770.

To obtain the polymer, 10 parts by weight of oil A and 1 part by weight of oil B and the photoinitiator are mixed, then crosslinking is carried out as mentioned previously.

The photoinitiator compounds by means of which the photoinitiator groups can be introduced into the crosslinkable liquid compositions described above comprise, on the one hand, a functional group intended to react with the SiH or Si-vinyl groups of PDMS oils, and, on the other hand, a photoinitiator group.

Such compounds can be obtained by functionalizing conventional photoinitiators, namely: any compound producing free radicals under irradiation, either by itself or by cooperation with another compound donating protons or electrons.

This means that the photoinitiators used, or photopolymerization initiators, can be both of photocleavable type and of photoactivatable type, with however a preference for those which are active to initiate the photopolymerization of the monomer for wavelengths d irradiation in the UV field. Such photoinitiators can be functionalized by techniques known to those skilled in the art.

Reference may usefully be made to the teaching of the following documents: - US Pat. No. 4,507,187 describing the manufacture of a photoinitiator of the aroyoyl formate type functionalized with alkenic or acetylenic groups;

- US Patents 4,477,326 and US 4,587,276 describing the obtaining of photoinitiators of the benzoin type functionalized with allylic groups;

- US patent 4536265 describing the production of acetophenones with olefinic or acetylenic functionality; and

- the document "Photoinitiator with functional group" JMS - Pure Appl - Chem A 31 (3) pp 305-318 (1994) - KOLAR, GRUBE, GREBER, which describes photoinitiators functionalized by a silyl group, namely 2-hydroxy (or 2-methoxy) -2-methyl-1- (4-dimethylsilyl) phenyl-propane-1 -one.

Among the photoinitiators which can be fixed in polymeric materials, in particular silicone, those corresponding to the formula are more particularly recommended:

in which :

R represents a hydrogen atom or a methyl group, Z is a divalent hydrocarbon chain containing from 1 to 10 carbon atoms, which can be interrupted by 1 to 3 atoms chosen from -O-, R '

- Si -, where R 'is independently a hydrogen atom or an R' alkyl group, preferably a C _j -C ₆ alkyl group, and better still a methyl group, and A _m is a group comprising a function

o

Preferably Z represents the following divalent chains

O

(CH ₂ ) _n , -, - CH ₂ O ₂ CH ₂ -, - CH ₂ n ₃ c O-} '—n (CH _j ) -

R "

- CH.CH, - 0— If -

R "'

in which R "and R '" independently of one another represent an alkyl group, preferably C _j -Cg, and in particular a methyl group, n _j and n ₂ are integers from 1 to 6, n ₃ and n ₅ are integers from 0 to 4, n ₄ is 0 or 1, and n ₆ is an integer from 0 to 5.

Preferably, the group A _m is chosen from the groups corresponding to the formulas:

O-RHO provided that Z has

O at least two carbon atoms

in which R _j , R ₂ , R ₃ and R ₄ , which may be identical or different, are chosen from hydrogen and alkyl groups having from 1 to 6 carbon atoms, preferably a methyl group.

Long-chain photoinitiators obtained by reacting one of the above-mentioned photoinitiators with a polysiloxane oil, preferably with a linear chain, can also be used by hydrosilylation reaction. Preferably, the polysiloxane oil is a PDMS oil whose molecular mass is between 132 and 50,000 g / mole, preferably between 250 and 10,000 g / mole.

Obtaining such photoinitiators is described in the article by KOLAR, GRUBE, GREBER, mentioned above, as well as in the article "Functional polysiloxanes with benzophenone side groups: a photochemical application as radical polymerisation macro-initiators Lydie Pouliquen, Xavier Coqueret, Alain Lablache-Combier, Claude Loucheux. Makromol. Chem. 113, 1273-1282 (1992).

The long chain photoinitiator is introduced into the PDMS oil at a concentration such that the fraction by weight of the groups functional photoinitiators is equal to that used for conventional photoinitiators, typically from 0.05 to 5% by weight of functional photoinitiator groups preferably from 0.05 to 2% by weight. When photoactivatable photoinitiators are used, the hydrogen or electron donor compound can be introduced into the swelling solution used in the first step of the hydrophilization process.

The donor compound can also be attached to the network of the PDMS matrix, that is to say introduced into the mixture of siloxane prepolymers, insofar as the donor compound has been previously functionalized.

In this case, the donor compound will be attached to the network of the silicone matrix by a covalent bond.

One can also fix this functionalized donor compound on a polysiloxane chain by hydrosilylation reaction and thus obtain a donor compound with a long polysiloxane chain, preferably PDMS, which, introduced into the mixture of siloxane prepolymers, will be physically retained in the silicone matrix. final. For the preparation of the long poly-siloxane chain donor compound, the same polysiloxane oil is used as that defined for the preparation of the long polysiloxane photoinitiator compound.

An example of a donor or co-initiator compound is ethyl dimethyl-amino-4 benzoate (DMABE).

A functionalized co-initiator which can be used is 4-dimethylvinylsilane-N, N-dimethylaniline

In general, the amount of co-initiator used depends on the amount of photoinitiator used. Concentrations are used in co-initiating units chosen from the same concentration ranges as the photoinitiators.

In the process of the invention, the step of curing the composition within the polymer matrix c) is preferably a step of photopolymerization of the impregnation composition.

The irradiation can be carried out by any light source emitting in the range of sensitivity of the photo-initiator used. It may be a mercury arc lamp, for preferred photosensitization compositions.

The impregnating solution contains a swelling solvent for the polymer matrix, which is preferably also capable of solubilizing the zwitterionic monomer. If desired, an additional solvent can be included to facilitate dissolution of the zwitterionic monomer.

As preferred solvent, for a hydrophilic matrix, mention may be made of water, alcohols, polyalkylene glycols such as ethylene glycol and methyl sulfoxide.

In the case where the polymer matrix is a hydrophobic material and more particularly a silicone, ethylene glycol and / or chloroform are preferably used as swelling solvent.

The impregnation solution can also contain other polymerizable comonomers, different from the zwitterionic monomers. which, for example, are of the same nature as those used to obtain the matrix, this in order to improve the mechanical properties of the final material and / or to increase the compatibility between the polymer network constituting the matrix and the network of zwitterionic polymer. The duration of the step of immersing the matrix in the impregnation solution is variable depending on the nature of the polymer matrix, but must be sufficient to allow swelling and impregnation of the matrix. Generally, this immersion step a) is between 5 and 30 minutes. As indicated previously, the curing step c) of the composition impregnated within the polymer matrix can be carried out thermally or photochemically. When thermal curing is used, thermal initiators are used in the impregnation solution, preferably thermal initiators which can be used at low temperature and in particular peroxides such as perkadox® or trigonox®. Preferably, however, the curing step is a photopolymerization step. In this case, the irradiation time generally varies from 1 minute to 1 hour.

The following examples illustrate the present invention. In these examples, unless otherwise indicated, all the percentages and parts are expressed by weight.

Examples of implementation of the invention

1) Lens treatment

Example 1

A VARIATIONS® progressive contact lens, sold by the company ESSILOR, with an optical power of -3 diopters, made of a copolymer of a methylmethacrylate (MMA) / N-vinylpyrrolidone (NVP) mixture is swelled in a solution. aqueous containing: 50% by weight of sulfobetaine SPV [1- (3-sulfopropyl) -2-vinyl-pyridinium-betaine], sold by the company RASCHIG.

0.2% by weight of polyoxyethylenediacrylate of molecular mass 400 (SARTOMER® 344 from the company CRAY-VALLEY).

0.1% by weight of thioxanthone QTX®.

0.1% by weight of methyldiethanolamine (MDEA).

for a period of 10 minutes.

The lens is then removed from the swelling solution and wiped with Joseph paper. (A simple draining may suffice if necessary). The contact lens is placed between two quartz blades maintained under slight pressure. Alternatively, a hemispherical support can be used.

The lens is then subjected to a homogeneous irradiation of a 200 watt HBO mercury vapor UV lamp for 30 minutes. Then, the excess raw material is removed by soaking the contact lens in a buffered solution for 30 minutes. The soaking solution is then discarded and replaced with a new buffered solution and the lens is left to soak again for 30 minutes.

Example 2

A contact lens of the FOCUS® brand with a power of -3 diopters, marketed by the company CIBA GEIGY, in VIFILCON® A material consisting of a HEMA (hydroxyethylmethacrylate) / NVP / MAA (methacrylic acid) copolymer, is treated with the same way and with the same solution as in Example 1.

For Examples 1 and 2, it can be seen, after examining the contact lenses at the end of the treatment, that they are not deformed and that their optical properties are not modified. 2) Determination of the anti-protein efficacy

The effectiveness of the anti-protein treatments is then measured as follows: 1) The contact lenses treated according to the method of the invention are incubated in a solution simulating the lacrimal medium. 2) Measurements are made at regular intervals to assess the amount of protein absorbed by the contact lenses. For this, measurements are carried out by spectrofluorimetry, that is to say that: a) the fluorescence of the proteins is caused by irradiation under UV at 280 nm of the contact lenses, b) the intensity is measured I of the fluorescence emission at 340 nm, the value of which is proportional to the amount of protein absorbed by the contact lenses.

The results of these measurements are collated in Figures 1 and 2.

FIG. 1 represents the intensity I (as a function of the incubation time) of the fluorescence emission of the lens of example 1 and of a VARIATION® lens which has not undergone the treatment according to the invention and subjected to the same incubation test.

FIG. 2 represents the intensity I of the fluorescence emission as a function of the incubation time of the lens of Example 3 and of a FOCUS® lens which has not undergone the treatment according to the invention and subjected to the same incubation test.

It can be seen in FIGS. 1 and 2 that the lenses treated according to the method of the invention exhibit reduced fouling with respect to the proteins. The polymeric materials incorporating zwitterions obtained by the process of the invention have good mechanical properties generally superior to those of the copolymers and are more homogeneous.

The solution simulating tears and its detailed preparation method are given below. The composition is as follows (in grams / liter)

Proteins: 5

=> Lysozyme (Sigma L6876) 2

=> Mucine (Sigma M1778) 1

=> Lactoferrin (Fluka 61324) 1

= Glycoprotein (Sigma G3643) 0.5

=> IgG (Fluka 56834) 0.3

=> Albumin (bovine, Sigma A3803) 0.2

Fat: 0.08

=> Cholesteryl linoleate (Sigma C0289) 0.024

=> Linalyl acetate (Aldrich L280-7) 0.02

=> Triolein (Sigma T7140) 0.016

=> Propyl oleate (Sigma) 0.012

=> Dicaproin (Sigma D5274) 0.0032

= »Undecylenic acid (Sigma U3252) 0.0032

=> Cholesterol (Sigma C8667) 0.0016

PBS buffer: Buffered phosphate knows (Polylabo)

(qs per 100 ml) HBSS: Hank's balanced knows (Sigma H1387)

with a PBS / HBSS 19/1 weight ratio.

Procedure for preparing the solution

Solution A is prepared by mixing the following constituents:

Propyl oleate (0.3 g), triolein (0.4 g), dicaproin (0.08 g), lynalyne acetate (0.5 g), then stirred.

A solution B is then prepared with 0.408 g of solution A; 0.012 g of cholesterol; 0.18 g of cholesteryl linoleate.

The mixture is stirred while slightly raising the temperature (30-35 ° C) for good dissolution. Then prepare a solution C from 8 mg of solution B, 100 mg of mucin; 0.32 mg of undecylenic acid, which is dissolved in 3 ml of buffer.

Finally, the final solution is prepared by dissolving the proteins one by one in a few ml of buffer solution, then they are incorporated into solution C and diluted with buffer. The mixture is left to stand overnight in the refrigerator and the pH is adjusted to 7.4 with a sodium hydroxide solution (IN).

Finally, the volume is made up to 100 ml by adding buffer.

This solution can be stored for 1 month in the refrigerator.

Experimental protocol for measuring a lens in spectrofluorimetry

1. Cuvette used for the measurement.

The tank is a Plexiglas® tank with a quartz slide. The lens is placed on a glass half-ball having the radius of curvature and the diameter of the lens bonded to a "lens-holder" Plexiglas® strip. The lens placed on this half-ball is positioned perfectly, in the same way as on an eye.

The coverslip, with the lens on the glass half-ball, is placed in the tank and finally the tank is filled with serum. The spectrofluorimeter measurement can then be performed.

2. Spectrofluorimeter.

The spectrofluorimeter is a Perkin Elmer LS-50B. The following parameters have been optimized to obtain good detection without signal saturation and minimal noise: Width of the excitation slot = 5 mm Width of the emission slot = 2.5 mm Scanning speed = 120 nm min. For the measurement of proteins, the excitation is made at 280 nm.

The intensity of the fluorescence emission is measured at 340 nm. 3. Experimental protocol.

To measure lenses by spectrofluorimetry, we proceed as follows on a series of lenses (3 to 5):

. Five consecutive measurements in spectrofluorimetry are carried out on the initial lens (stored in serum) while exciting at 280 nm. The lens is rinsed in 5 ml of serum, placed on the glass half-ball in the tank by means of tweezers. The coverslip is introduced into the tank, then the tank is filled with serum. The lens is rinsed in serum between each measurement and then randomly repositioned on the glass half-ball.

. The intensities of the spectra at 340 nm are noted and the average initial value is deduced therefrom. . The lens is incubated in 1 ml of teardrop model with stirring in an oven at 35 ° C (eye temperature), for several hours or several days.

. The lens is rinsed in serum (100 ml) with stirring for 15 minutes. . Five new measurements of the fouled lens are carried out in spectrofluorimetry, exciting at 280 nm, in the same way as on the blank lens (rinsing and repositioning). . The intensity of the peak at 340 nm is noted for each measurement from which the initial average intensity is subtracted (blank spectrum). We calculate an average characteristic of fouling for a given material.

Claims

1. A method of manufacturing a transparent polymer material with a low tendency to accumulate deposits, characterized in that it comprises: a) the immersion of a transparent polymer matrix in a solution comprising a swelling solvent and a curable composition, the curable composition comprising: a polymerizable monomer comprising at least one zwitterionic group; and a monomer crosslinking agent, for swelling the polymer matrix and impregnating it with said composition; b) optionally removing the polymer matrix, swollen and impregnated with said composition, from the solution; and c) curing said composition within the polymer matrix, this curing being carried out in the presence of a polymerization initiator initially present in the matrix or in the swelling solution.

2. Method according to claim 1, characterized in that the transparent polymer matrix is a hydrophilic or hydrophobic matrix.

3. Method according to claim 2, characterized in that the polymer matrix is a polymer or copolymer based on alkyl (meth) acrylate, hydroxy (alkyl) (meth) acrylate, polyhydroxy (alkyl) (meth) acrylate), N-vinyl lactam, vinyl monomers, (alkylene glycol) (meth) acrylate, poly (alkylene glycol)

oleoxylated (meth) acrylate, of polyorganosiloxane, or mixtures thereof.

4. Method according to any one of claims 1 or 3, characterized in that the concentration of monomers comprising at least one zwitterionic group in the impregnation solution is between 5 and 95% by weight, preferably 25 to 75% by weight, and better still from 40 to 60% by weight, relative to the total weight of the solution.

5. Method according to any one of claims 1 to 4, characterized in that the concentration of the crosslinking agent is between 0.1 and 5% by weight relative to the total weight of the impregnation solution.

6. Method according to any one of the preceding claims, characterized in that the polymerizable monomer comprising at least one zwitterionic group is a sulfobetaine.

7. Method according to claim 5, characterized in that the polymerizable monomer comprising at least one zwitterionic group is chosen from N, N-dimethyl N-methacryloxyethyl N- (3-sulfopropyl) ammonium-betaine, NN-dimethyl-N -methacrylamido -propyl-N- (3-sulfopropyl) ammonium-betaine, and l- (3-sulfopropyl) -2- vinyl-pyridinium-betaine.

8. Method according to any one of the preceding claims, characterized in that the crosslinking agent is chosen from poly (oxyethylene) dimethacrylates.

9. Method according to any one of the preceding claims, characterized in that the swelling solvent for the transparent polymer matrix is chosen from water, alcohols, polyalkylene glycols, dimethyl sulfoxide, and mixtures thereof.

10. Method according to any one of the preceding claims, characterized in that the step of immersing the polymer matrix in the impregnation solution has a duration of 5 to 30 minutes.

11. Method according to any one of the preceding claims, characterized in that the polymerization initiator is a thermal polymerization initiator, a photopolymerization photoinitiator or a mixture of the two.

12. The method of claim 11, characterized in that the polymerization initiator is a photoinitiator and the curing step c) of the composition within the polymer matrix is a photopolymerization step.

13. The method of claim 12, characterized in that the irradiation time of the photopolymerization step is between 1 minute and 1 hour.

14. Method according to claim 11, characterized in that the polymerization initiator is a photocleavable or photoactivatable photoinitiator.

15. The method of claim 14, characterized in that the photoinitiator is fixed in the polymer matrix.

16. Method according to claim 15, characterized in that the polymer matrix is a silicone.

17. Method according to any one of the preceding claims, characterized in that the polymer matrix is a contact lens or an intraocular implant.

18. Transparent polymer material having a low tendency to deposit accumulation, characterized in that it comprises a transparent polymer matrix and an interpenetrating network of a polymer comprising zwitterionic groups, the interpenetrating network of the polymer comprising zwitterionic groups being obtained by the process according to any one of Claims 1 to 16.

19. Contact lens made of the material according to claim 18.

20. Intraocular implant made of the material according to claim 19.