FR2772033A1 - PROCESS FOR PRODUCING A TRANSPARENT POLYMERIC MATERIAL RESISTANT TO THE DEPOSITION OF PROTEINS, MATERIAL OBTAINED BY THIS PROCESS, CONTACT LENSES AND INTRAOCULAR IMPLANTS MADE OF THIS MATERIAL - Google Patents

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 of making a transparent polymeric material
resistant to protein deposition, material obtained by this process,
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 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 process for 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 sand hardened 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) 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 polymer materials are well known in the art and mention may be made, among the polymers which can be used in the process of the present invention, of polymers and copolymers based on alkyl (meth) acrylate, in particular on C1-C4 alkyl such as as methyl (meth) acrylate, hydroxy (alkyl) (meth) acrylates, in particular alkyl in
C4 such as hydroxyethylmethacrylate (HEMA) and hydroxypropylmethacrylate (HPMA), polyhydroxy (alkyl) (meth) acrylates such as polyhydroxyethylmethacrylates, N-vinyl lactams such as Nvinylpyrrolidone, 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 or propoxylated.

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

 Polydimethylsiloxane (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 (silbionet)).

 Oil A consists of mono and divinyl polydimethylsiloxanes and a platinum catalyst.

 This part contains approximately 3.10 × 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, there may be mentioned N- (3-sulfopropyl) -methacroyloxyethyl-N, N ammonium-betaine (SPE), N- (3 -sulfopropyl) -N-methacrylamidopropyl-N, N-dimethylammonium -betaine (SPP), 1- (3 -sulfopropyl) -2- vinyl-pyridinium-betaine (SPV), N-methacryloyloxyethyl-N, N- dimethyl-N, 2-ethylcarboxy-betaine, N- (3 -carboxypropyl) -N-methylaminoethylmethacrylate, N- (3-carboxypropyl) -N-methylamino- methacryloyloxyethyl-N, N-dimethylammonium-betaine (CPE), N- (3c arboxypropyl) aminoethylmethacrylate, and 2- (methacryloyl) ethyl- 2- (trimethylammonium) ethylphosphate.

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

 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 initiators or initiators of thermal polymerization 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 both of photocleavable type and 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 American patent US-A-4,791,213, the maximum absorption of which is 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 alkylamine or oxy alkylamine 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 1.102 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, 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 groups or photoinitiator fragments distributed homogeneously throughout 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 photoamorcour 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 nature of the network of the crosslinked silicone polymer of the matrix.

 However, whatever the fixing technique used, the photoinitiator groups remain fixed in the polysiloxane matrix even when the latter is subjected to extraction treatments with solvents. 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 represented below.
Constituent A
Constituent B

 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, hexachloroplatinic 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 2500C depending on the concentration and the type of catalyst used.

Preferred temperatures range from 50 "C to 1500C.

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 (silbione8) and the photoinitiator functionalized in the desired proportions.

 Oil A consists of mono- and divinyl PDMS and a platinum catalyst. This part contains around 3.10 x 10-4 vinyl functions per gram of RTV70 141 A and its number average molecular weight is 31200.

 Oil B is preferably a hydrogen methyl PDMS and contains 4.07 × 10 −3 SiH functions per gram of RTV70 141 B and its number average molecular mass 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 Sivinyl groups of the 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 in the UV field.

 Such photoinitiators can be functionalized by techniques known to those skilled in the art.

We can usefully refer 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 JMS "Photoinitiator with functional group" document
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.

où R' est indépendamment un atome d'hydrogène ou un groupe alkyle, de préférence un groupe allyle en C1-C6, et mieux encore un groupe méthyle, et
Arn est un groupement comportant une fonction

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-,

where R 'is independently a hydrogen atom or an alkyl group, preferably a C1-C6 allyl group, and better still a methyl group, and
Arn is a group with a function

Preferably Z represents the following divalent chains

 in which R "and R" 'independently of one another represent an alkyl group, preferably C1-C6, and in particular a methyl group, nl and n2 are integers from 1 to 6, n3 and n5 are integers from 0 to 4, n4 is 0 or 1, and n6 is an integer from 0 to 5.

à condition que Z comporte au moins deux atomes de carbone

Preferably, the Arn group is chosen from the groups corresponding to the formulas

provided that Z has at least two carbon atoms

 in which R1, R2, R3 and R4, 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 previously, as well as in the article "Functional polysiloxanes with benzophenone side groups: a photochemical application as radical polymerization 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 oil
PDMS at a concentration such that the weight fraction of the photoinitiator functional groups is equal to that used for conventional photoinitiators, typically from 0.05 to 5% by weight of photoinitiator functional 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 final silicone matrix. 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 dimethylamino-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, polyallcylene 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 may also contain other polymerizable comonomers, different from the zwitterionic monomers which, for example, are of the same nature as those used for obtaining 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 the 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) Treatment of lenses
Example 1
A VARIATIONS "progressive contact lens, marketed by the company ESSILOR, of optical power -3 diopters, made of a copolymer of a methyl methacrylate (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 molecular weight polyoxyethylene diacrylate
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 of raw material is evacuated by soaking the contact lens in a

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 are incubated
of the invention, in a solution simulating the lacrimal medium.

2) Measurements are carried out at regular intervals allowing
assess the amount of protein absorbed by the lenses
contact.

For this, measurements are made by spectrofluorimetry, that is to say that
a) the fluorescence of the proteins is caused by irradiation
contact lenses under UV at 280 nm,
b) the intensity I of the fluorescence emission is measured at
340 nm, the value of which is proportional to the amount of
protein absorbed by 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 VARIATIONS lens which has not undergone the treatment according to the invention and subjected at 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 (F1uka56834) 0.3 (Fluka 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 Phosphate Buffered salt (Polylabo)
(qs per 100 ml) HBSS: Hank's balanced salt (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), dicaproine (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 a solution C is prepared 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. It is left to stand overnight in the refrigerator and the pH is adjusted to 7.4 with a sodium hydroxide solution (1N).

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 PlexiglasB 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 Plexiglas "lens holder" 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 excitation slot = 5 mm
Transmission slot width = 2.5mm
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, proceed as follows on a series of lenses (3 to 5). Five consecutive measurements are made in spectrofluorimetry on the initial lens (stored in serum) with excitation 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 350C (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). An average characteristic of fouling for a given material is calculated.

Claims (20)

 1. A method of manufacturing a transparent polymer material having a low tendency to accumulate deposits, characterized in that it comprises:  a) immersing 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) the curing of 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, oleoxylated poly (alkylene glycol) (meth) acrylate, 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) arnnonnon-betaine, NN-dimethyl-N- methacrylamido -propyl-N- (3-sulfopropyl) ammonium-betaine, and 1- (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, dimethylsulfoxide, 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.