ACRYLIC COPOLYMER FOR THE MANUFACTURE OF INTRAOCULAR LENSES

Abstract

The material according to the invention is a crosslinked acrylic copolymer for the manufacture of intraocular lenses (1). It is obtained from a mixture of monomers containing at least: - 2-phenoxyethyl acrylate (2PEA) and / or 2-phenoxy-(2-ethoxy)4-acrylate (4PEA); - phenoxyethyl methacrylate (MAPE) and / or benzyl methacrylate; - a hydroxylated acrylate and / or a hydroxylated methacrylate, the glass transition temperature (Tg) of which is below 20°C; - ethoxyethyl methacrylate (MAEE); and - a polyethylene glycol diacrylate and / or dimethacrylate comprising 3 to 5 ethoxyl groups. Figure for the abstract: Fig 1

Description

Title of the invention: ACRYLIC COPOLYMER FOR THE PRODUCTION OF INTR AO CUL ARY LENSES Technical field

[0001] The present invention relates to a new acrylic polymer material, perfectly suited for the production of intraocular lenses and whose mechanical properties are not very sensitive to the presence of water, despite a water uptake of between 5% and 6% at 35°C. This acrylic polymer material retains comparable mechanical properties, in particular in terms of its rigidity, whether in the dry state, in the operating room for example, or in the wet state, once implanted in the eye of a patient.

[0002] The invention also relates to a method of manufacturing this polymer material, as well as intraocular lenses made from such a polymer material. Prior art

[0003] Intraocular lenses are ophthalmic implants or prostheses that are surgically placed in the eye of patients suffering, for example, from cataracts, to replace their defective lens.

[0004] Once implanted in the eye, the intraocular lens replaces the patient's crystalline lens. It must therefore perform all the functions that were previously performed naturally by the crystalline lens. It must thus perform the optical functions of focusing light rays on the retina and accommodation, which are the main functions of the crystalline lens.

[0005] Due to their nature, which means that they are intended to be permanently implanted inside a human eye, the optical function that they must perform and their very restrictive fitting process, intraocular lenses are subject to numerous constraints and must simultaneously meet numerous criteria to be deemed satisfactory.

[0006] From an optical point of view, intraocular lenses must be made of a transparent material with a sufficient optical index, i.e. greater than 1.5, capable of focusing on the macula once the lens is in place, while having minimal bulk.

[0007] This material must allow high-precision machining to obtain the necessary optical quality.

[0008] On the other hand, the material used must be compatible with permanent implantation of the lenses in the human eye and must not be cytotoxic. It must not, over time, diffuse toxic products so as not to cause inflammation or necrosis.

[0009] Furthermore, in order for the lens to be fitted without difficulty, the material must be sufficiently flexible to be able to be folded, rolled up on itself and strongly stretched, without breaking, so as to pass through a very small incision in the eye. Once in the eye, it must then be able to unfold on its own, quickly and without remaining stuck to itself, in order to position itself correctly in the crystalline sac.

[0010] The choice of monomers used must not lead to the production of a polymer material which no longer meets one or more of these criteria.

[0011] An objective of the invention is to provide a new polymer material, which allows the production of soft intraocular lenses fulfilling all of these conditions.

[0012] Numerous intraocular lenses, of varied shape and composition, have been described in the prior art. Among these, lenses made of so-called "hydrophobic" plastic materials have been proposed, and in particular lenses made from acrylic polymers.

[0013] These “hydrophobic” materials are conventionally defined by a water uptake of less than 5% at 35°C. They have many advantages, including that of having specific characteristics which depend little on the quantity of water absorbed.

[0014] The flexibility of these materials depends on the temperature at which they are found. They have a glass transition temperature (Tg) below which they are hard and can be machined and above which they become soft, deformable and elastic.

[0015] For the production of intraocular lenses, a material must be chosen having a low glass transition temperature and a low modulus of elasticity above this temperature, so that the resulting lens is flexible enough to be rolled and stretched at operating room temperature, i.e. approximately 18 to 20°C.

[0016] Previous patent applications WO 2015 / 128555A1 and WO 2017 / 0814225 give examples of acrylic polymer materials suitable for the production of intraocular lenses.

[0017] However, if these materials are satisfactory when their water uptake at 35°C is significantly less than 5%, problems have been noted with materials for which this value is slightly greater than 5%.

[0018] It has been found that known acrylic polymer materials which have a water uptake of between 5 and 6% at 35°C exhibit significant variations in mechanical properties between their dry state at 20°C (ambient conditions corresponding substantially to those of an operating room), and their hydrated state at 35°C (conditions (corresponding substantially to those found in a human eye), which makes them difficult to use as intraocular lenses.

[0019] Indeed, when they are placed in a warm and humid environment, as is the case in a human eye, their rigidity decreases very sharply. These materials, which must be chosen with a low modulus of elasticity at 20°C and in the ambient dry state in order to be able to be rolled and stretched during their implantation, become very soft at 35°C in the humid state, their modulus of elasticity decreasing very sharply.

[0020] However, when implanted in a patient's eye, intraocular lenses must have sufficient rigidity to keep the lens bag taut by means of their haptics and to remain in place despite the patient's movements. The excessive flexibility of these materials in a warm and humid state can prevent them from fulfilling these holding functions satisfactorily.

[0021] Other polymer materials are also known which are used for the production of intraocular lenses, such as for example that developed by the company SANTEN ™ and marketed under the name ENVISTA ™, which have satisfactory rigidity in the wet state at 35° allowing them to be held well once implanted in the patient's eye.

[0022] However, these materials are so rigid in the ambient dry state that they cannot be implanted in the dry state under normal operating room conditions. They must therefore be packaged and stored in an aqueous solution in order to be used in a hydrated form and thus be flexible enough to be rolled and stretched.

[0023] But this packaging in an aqueous solution causes particularly heavy health constraints. Indeed, in addition to the lens which must be sterile, it is necessary to guarantee that the aqueous solution does not contain cytotoxic substances and that bacteria do not develop there, to limit the risks of inflammation of the eye.

[0024] An aim of the invention is to provide a new acrylic polymer material suitable for the production of intraocular lenses which can be implanted in the dry ambient state under the usual conditions of an operating room (approximately 20°C).

[0025] Another aim of the invention is to provide a new acrylic polymer material suitable for the production of intraocular lenses, the rigidity of which is less sensitive to the presence of water, despite a water uptake of between 5 and 6% at 35°C.

[0026] Thus, the decrease in the modulus of elasticity of the material according to the invention, when it passes from the ambient dry state at 20°C to the wet state at 35°C, remains limited. It can therefore have a sufficiently low modulus of elasticity in the ambient dry state to be compatible in the dry state with the lens implantation process, and soften only slightly when it is in the wet state in the eye of a patient and thus guarantee satisfactory maintenance in the lens bag.

[0027] For this, the invention provides a new acrylic polymer material, suitable for the production of intraocular lenses, which is a copolymer prepared from a mixture of monomers comprising at least:

[0028] - 2-phenoxy-ethyl acrylate (2PEA) and / or 2-phenoxy-(2-ethoxy)4-acrylate (4PEA); - phenoxyethyl methacrylate (MAPE) and / or benzyl methacrylate; - a hydroxylated acrylate and / or a hydroxylated methacrylate, the glass transition temperature (Tg) of which is less than 20°C, preferably less than 15°C and even more preferably less than 10°C; - ethoxyethyl methacrylate (EMAE); and - a polyethylene glycol diacrylate comprising 3 to 5 ethoxyl functions and / or a polyethylene glycol dimethacrylate comprising 3 to 5 ethoxyl functions.

[0029] According to one embodiment, the mixture of monomers comprises at least 80%, preferably at least 90%, by mass of acrylic and / or methacrylic monomers.

[0030] According to one embodiment, 2-phenoxy-ethyl acrylate (2PEA) and / or 2-phenoxy-(2-ethoxy)4-acrylate (4PEA) represents between 7 and 36%, preferably between 10 and 20% and more preferably between 11 and 15% by mass of the monomer mixture.

[0031] According to one embodiment, phenoxyethyl methacrylate (MAPE) and / or benzyl methacrylate represents between 15 and 45%, preferably between 25 and 40% and more preferably between 29 and 35% by mass of the monomer mixture.

[0032] According to one embodiment, the hydroxylated acrylate is 4-hydroxy-butyl acrylate (4HBA) or hydroxy-hexyl acrylate.

[0033] According to one embodiment, the hydroxylated methacrylate is a polyethylene glycol monomethacrylate comprising one to three ethoxyl functions or butanediol monomethacrylate.

[0034] According to one embodiment, the hydroxylated acrylate and / or the hydroxylated methacrylate represents between 20 and 40%, preferably between 25 and 35% and more preferably between 28 and 35% by mass of the monomer mixture.

[0035] According to one embodiment, the ethoxyethyl methacrylate (EAM) represents between 5 and 30%, preferably between 10 and 25% and more preferably between 15 and 20% by mass of the monomer mixture.

[0036] According to one embodiment, the polyethylene glycol diacrylate comprising from 3 to 5 ethoxyl functions is triethylene glycol diacrylate, and the polyethylene glycol dimethacrylate comprising from 3 to 5 ethoxyl functions is triethylene glycol dimethacrylate.

[0037] According to one embodiment, the polyethylene glycol diacrylate comprising from 3 to 5 ethoxyl functions and / or polyethylene glycol dimethacrylate comprising 3 to 5 ethoxyl functions represents between 3 and 6% and preferably between 3.5 and 6% by mass of the monomer mixture.

[0038] According to one embodiment, the mixture of monomers further comprises one or more polyethylene glycol dimethacrylates comprising from 10 to 30 ethoxyl functions.

[0039] According to a variant of this embodiment, the polyethylene glycol dimethacrylate(s) comprising from 10 to 30 ethoxyl functions represents up to 2% and preferably up to 1% by mass of the monomer mixture.

[0040] According to one embodiment, the mixture of monomers further comprises cinnamic alcohol or a transfer agent, preferably cinnamic alcohol.

[0041] In this case, the cinnamic alcohol is preferably found in an amount of between 0.1% and 5%, more preferably between 0.2% and 2% by mass of the monomer mixture and even more preferably in an amount representing approximately 0.5% by mass of the monomer mixture.

[0042] According to one embodiment, the monomer mixture further comprises a UV-absorbing monomer, preferably in an amount of between 0.1 and 2% by mass of the monomer mixture and more preferably in an amount representing approximately 1% by mass of the monomer mixture.

[0043] The invention also teaches a method of manufacturing such an acrylic polymer material. This method comprises the following steps:

[0044] . a mixture of monomers is produced containing at least:

[0045] - 2-phenoxy-ethyl acrylate (2PEA) and / or 2-phenoxy-(2-ethoxy)4-acrylate (4PEA); - phenoxyethyl methacrylate (MAPE) and / or benzyl methacrylate; - a hydroxylated acrylate and / or a hydroxylated methacrylate, the glass transition temperature (Tg) of which is less than 20°C, preferably less than 15°C and even more preferably less than 10°C; - ethoxyethyl methacrylate (EMAE); and - a polyethylene glycol diacrylate comprising 3 to 5 ethoxyl functions and / or a polyethylene glycol dimethacrylate comprising 3 to 5 ethoxyl functions;

[0046] . at least one initiator compound is added to said mixture; . the said mixture is polymerized by radical means, in a single polymerization step, so as to obtain by this polymerization a crosslinked copolymer.

[0047] The invention finally provides an intraocular lens made of an acrylic polymer material as set out above. Brief description of the figures

[0048] Other characteristics and advantages of the invention will appear on reading the detailed description which follows, in particular the role, the preferential nature and the quantity of each of the monomers and other constituents of the mixture making it possible to obtain the material according to the invention.

[0049] To facilitate the reader's understanding, this description is accompanied by the following attached drawings as an example:

[0050] [Fig.l]

[0051] [Fig.2] Figures 1 and 2 are schematic views of two examples of intraocular lenses that can be made from the material according to the invention; Detailed description of the invention

[0052] In this patent application, the glass transition temperature (Tg) of a monomer will be defined as that of the corresponding homopolymer, measured by the method and under the conditions defined by the international standard ISO 6721-1.

[0053] In the same way, the elastic modulus of a polymer will be defined as that measured by the method and under the conditions defined by the international standard ISO 6721-1.

[0054] Finally, the percentage of water uptake of a polymer at 35°C will be defined as that measured by the method and under the conditions defined by the international standard ISO 10339.

[0055] In Figures 1 and 2, lenses 1 are shown which conventionally comprise a central optical part 2, substantially in the form of a disc and with a bi-convex profile. This corrective optical part 2 must be positioned perpendicularly and centrally with respect to the optical axis of the eye.

[0056] From this optical part 2 extend lateral extensions called haptics 3, the role of which is to stretch the walls of the crystalline sac and to ensure correct positioning of the lens relative to them.

[0057] In [Fig.l], there are two of these haptics 3. They are arranged diametrically opposite each other and have the shape of a curved arm, each going in an opposite direction.

[0058] The lens of [Fig.2] comprises four haptics 3 in the form of a ring pierced with a central orifice 4. These haptics 3 are regularly distributed around the periphery of the optical part 2.

[0059] The haptics 3 are connected to the central optical part 2 by a junction zone 5 forming a hinge which generates a spring effect by elastic return of the material to unfold the lens when it is implanted in the eye of a patient.

[0060] In the examples shown, the haptics 3 are made in one piece with the part optics 2 of the lens 1. This type of lens is called a “monobloc lens”. The material according to the invention is particularly suitable for producing such intraocular lenses 1, although other configurations are possible.

[0061] The polymer material according to the invention is preferably obtained by radical polymerization from a mixture of acrylic or methacrylic monomers for the most part, that is to say comprising one or more groups of acrylic or methacrylic type or derivatives thereof.

[0062] Preferably, the monomer mixture even comprises more than 80%, or even more than 90%, by mass of acrylic or methacrylic monomers.

[0063] According to the invention, the monomer mixture comprises one or more arylalkoxy-acrylates in the form of 2-phenoxy-ethyl acrylate (commonly called 2PEA), or 2-phenoxy-(2-ethoxy)4-acrylate (usually called 4PEA) or a mixture of the two.

[0064] These arylalkoxy-acrylates preferably represent between 7 and 36%, preferably between 10 and 20% and even more preferably between 11 and 15% by mass of the mixture of monomers.

[0065] The monomer mixture also comprises one or more arylalkoxy-methacrylates in the form of phenoxy-ethyl methacrylate (commonly called MAPE), or benzyl methacrylate, or a mixture of the two.

[0066] These arylalkoxy-methacrylates preferably represent between 15 and 45%, preferably between 25 and 40% and even more preferably between 29 and 35% by mass of the monomer mixture. A preferred value is for example close to 33%.

[0067] These arylalkoxy-acrylates and arylalkoxy-methacrylates are hydrophobic monomers which make it possible to obtain a final polymer with a high optical index. They also make it possible to increase the glass transition temperature (Tg) of the resulting polymer to increase its rigidity.

[0068] The monomer mixture also contains at least one hydroxylated acrylate or hydroxylated methacrylate or a mixture of the two.

[0069] These hydroxylated monomers increase the surface tension and the affinity of the surface with water of the resulting polymer, which reduces the stickiness of the material in the presence of water. They also make it possible to reduce the phenomenon of "glistening".

[0070] In order to be able to obtain the indicated properties of low sensitivity to the presence of water, these hydroxylated monomers must be chosen with a relatively low glass transition temperature (Tg), i.e. less than 20°C, preferably less than 15°C and even more preferably less than 10°C, or even negative.

[0071] For example, the monomer solution does not contain hydroxyethyl methacrylate (HEMA), because its Tg is close to 100°C.

[0072] The hydroxylated acrylate used is for example 4-hydroxy-butyl acrylate (4HBA) or hydroxy-hexyl acrylate.

[0073] The hydroxylated methacrylate used may be, for example, a polyethylene glycol monomethacrylate comprising one to three ethoxyl functions or butanediol monomethacrylate.

[0074] Preferably, the hydroxylated acrylate and / or the hydroxylated methacrylate together represent between 20 and 40%, preferably between 25 and 35% and more preferably between 29 and 35% by mass of the monomer mixture.

[0075] With such proportions of these hydroxylated monomers in the mixture before polymerization, the resulting polymer material has a suitable surface tension and does not whiten upon prolonged contact with water at 35°C.

[0076] The monomer mixture also contains ethoxyethyl methacrylate (EAEM) in a proportion preferably between 5 and 30%, preferably between 10 and 25% and more preferably between 15 and 20% by mass of the monomer mixture.

[0077] This monomer is a chain extender whose function is to create distance between the aromatic monomers of the network which are highly hindered by their aryl function, which reduces the overall steric hindrance of the polymer chain.

[0078] It thus improves the deformability of the resulting polymer and its resistance to rupture, without generating additional water uptake.

[0079] The mixture also contains crosslinking compounds which make it possible to obtain a three-dimensional macromolecular network after polymerization. These are difunctional monomers of the ethoxylated diol diacrylate and / or ethoxylated diol dimethacrylate type, used alone or as a mixture.

[0080] These crosslinking compounds contain ethoxyl functions so as not to increase the glass transition temperature of the final material and simultaneously to maintain a level of hydrophilicity homogeneous with the rest of the composition.

[0081] The ethoxylated diol diacrylates used are polyethylene glycol diacrylates comprising 3 to 5 ethoxyl functions, for example triethylene glycol diacrylate (Tridia) or tetraethylene glycol diacrylate (Tetradia) or a mixture of the two.

[0082] The ethoxylated diol dimethacrylates used are polyethylene glycol dimethacrylates comprising 3 to 5 ethoxyl functions, for example triethylene glycol dimethacrylate (Tridima) or tetraethylene glycol dimethacrylate (Tetradima) or a mixture of the two.

[0083] Preferably, the monomer mixture contains only dimethacrylates of polyethylene glycol as crosslinker.

[0084] When the monomer mixture contains both polyethylene glycol diacrylates and polyethylene glycol dimethacrylates as crosslinker, the relative proportion between the two in the monomer mixture is preferably close to % acrylates to ¾ methacrylates.

[0085] Advantageously, the mixture of monomers may also contain one or more polyethylene glycol dimethacrylates comprising from 10 to 30 ethoxyl functions, defined by CAS number 41637-38-1.

[0086] These monomers are present in small quantities in the mixture and preferably represent up to 2%, preferably up to 1% by mass of the monomer mixture.

[0087] These monomers act as surfactants whose function is to limit the self-adhesive nature of the polymer surface when it is folded back on itself. Indeed, thanks to their numerous ethoxyl functions, they create nano-reliefs on the surface of the polymer which reduce the adhesive force of the smooth surface of the hydrophobic acrylic polymer. An intraocular lens made from this material can thus deploy quickly when released into a patient's eye without its haptics remaining stuck to the central optical part of the lens.

[0088] In order to improve the ability of this material to deform without breaking at the lens application temperatures, without making it sticky, the monomer mixture may also contain a transfer agent, for example of the thiol type or preferably cinnamic alcohol, which acts as a terminating agent during radical polymerization.

[0089] By locally interrupting the formation of the three-dimensional mesh during polymerization, such compounds lead to the formation of localized pendant chains. The resulting mesh is thus looser and capable of stretching further without breaking for a high crosslinking rate and elasticity.

[0090] To obtain a satisfactory result, a quantity of cinnamic alcohol of between 0.1% and 5%, more preferably between 0.2% and 2%, and preferably substantially equal to 0.5%, by mass of the monomer mixture is preferably used.

[0091] Preferably, the monomer mixture further comprises a UV-absorbing monomer in order to protect the patient's eye, preferably in an amount of between 0.1 and 2% by mass of the monomer mixture and more preferably in an amount representing approximately 1.5% by mass of the monomer mixture.

[0092] This is for example 2-[3-(2H-benzotriazol 2 yl)-4-hydroxyphenyl]ethyl-methacrylate, or a derivative of tetrahydroxy-benzophenone in particular 2,2,4,4 tetrahydroxy-benzophenone.

[0093] Any other monomer or any other polymerizable or non-polymerizable constituent imaginable by those skilled in the art, of any function, may be added to the mixture, as long as its presence does not modify the general properties of the resulting polymer material in a way that makes it unsuitable for the production of intraocular lenses.

[0094] In addition to these monomers, the initial mixture may contain a certain number of additional compounds of a different nature, for example necessary for the proper progress of the reaction.

[0095] It thus comprises one or more initiator compounds, used to initiate the polymerization reaction, such as a peroxide in particular.On peut citer à titre d’exemple le tert-amyl-peroxy-2-ethyl-hexyl-carbonate également appelé TAEC, le tert-butyl peroxy-2-ethylhexanoate, le l,l-ditertio-butyl-peroxy-3,3,5-trimethylcyclohexane, le 1,1-ditertio-butyl-peroxycyclohexane, le tertio-butyl-peroxy-3,3,5-trimethylhexanoate, le tertiobutyl-peroxy-isopropylcarbonate, le dicumyl-peroxide, le tert-bu-tylcumyl-peroxide, le di-tert-amyl-peroxide, le tert-butyl-3-isopropenyl-cumyl-peroxide, le dioctananoyl-peroxide, le didecanoyl-peroxide, le tert-butyl-peroxy-2-ethylhexanoate, le tert-amyl-peroxy-2-ethylhexanoate, le tert-butyl-peroxy-3,5,5-trimethylhexanoate, 2,5-dimethyl-2,5-di(benzoylperoxy)hexane, le tert-amyl-peroxyacetate, le tert-butyl-peroxypivalate, le tert-amyl-peroxypivalate, le tert-butyl-peroxybenzoate, le tert-amyl-peroxybenzoate; le tertio-butyl-peroxy-2-ethylhexyl carbonate, le tertio-amyl peroxy-2-ethylhexyl carbonate, ou le tertio-butyl-peroxy-isobutyrate. .

[0096] This or these compounds are added to the mixture in very small quantities, the mixture comprising for example between 0.3 and 2% by mass of initiator compound.

[0097] In order to make this description more complete, an example of a process for obtaining an acrylic polymer material according to the invention will now be described.

[0098] To carry out the desired polymerization, we begin by mixing together all the monomers necessary for the reaction.

[0099] Advantageously, when they are in the liquid state, the monomers are soluble in each other and simple stirring is sufficient to produce a homogeneous mixture of them.

[0100] Other useful compounds, which are not monomers, may be added to the mixture. This is, for example, a transfer agent.

[0101] To trigger the polymerization reaction, the necessary initiator compound(s) are then added to this mixture.

[0102] The polymerization is then carried out by radical means, in a single step.

[0103] This is a mass polymerization, without solvent and with all the reagents present from the start, with an appropriate dosage to obtain the final polymer with all the desired properties, in a single operation.

[0104] For this, small quantities of the monomer mixture are advantageously placed in molds and heated to a temperature of between 60 and 120°C depending on the peroxide chosen, for a duration of, for example, between 2 and 6 hours.

[0105] Once the reaction is complete and after cooling, the polymer is demolded.

[0106] The molds are preferably chosen so as to obtain, after demolding, polymer blocks of generally cylindrical shape of low height, of the “token” or “puck” type. Such a shape is perfectly suited to subsequent machining of these polymer blocks in order to obtain intraocular lenses.

[0107] Of course, direct molding of intraocular lenses is also possible with a mold adapted to the chosen polymerization temperature range.

[0108] The polymer pallets are then purified, in order to remove unreacted monomers and impurities and residual products originating in particular from the synthesis of each of the monomers used. This purification can preferably be carried out by leaching.

[0109] After this purification step, a polymer material is obtained which has the properties indicated in the present application.

[0110] The polymer material discs are then ready to be machined, at a temperature below the glass transition temperature of the polymer, to produce the intraocular lenses according to the invention.

[0111] In order to fully describe the invention, several examples of acrylic polymer material according to the invention are detailed below.

[0112] These materials were all obtained by radical polymerization, from the following monomer mixtures, the quantities of which are expressed as mass percentages of the monomer mixture before polymerization.

[0113] From these materials intraocular lenses have been produced. Examples

[0114] [Tables 1] MONOMERS: (% by mass) Formula 1 Formula 2 Formula 3 Formula 4 2 phenoxy-ethylacrylate (2PEA) 7% 35.8% 28% 8.5% phenoxy-ethyl methacrylate (MAPE) 35% 18% 25% 33% 4-hydroxy-butyl-acrylate (4HBA) 32% 33% 30% 32% ethoxy-ethyl methacrylate (MAEE) 20% 7% 10% 20% triethylene glycol dimethacrylate 4% 4.5% 4.5% 4.5% cinnamic alcohol 0.5% 0.5% 0.5% 0.5% anti-UV compound 1.5% 1.2% 1.2% 1.5%

[0115] [T ables 2] MONOMERS: (% by mass) Formula 5 Formula 6 Formula 7 Formula 8 2 phenoxy-ethylacrylate (2PEA) 12% 12.4% 14.8% 14.3% phenoxy-ethyl methacrylate (MAPE) 32.6% 32.5% 32.5% 32.5% 4-hydroxy-butyl-acrylate (4HBA) 31.5% 31.4% 28.6% 28.6% ethoxy-ethyl methacrylate (MAEE) 18.3% 17.8% 18.2% 18.2% triethylene glycol dimethacrylate 3.6% 3.9% 3.9% 4.4% cinnamic alcohol 0.5% 0.5% 0.5% 0.5% anti-UV compound 1.5% 1.5% 1.5% 1.5%

[0116] [Tables3] MONOMERS: (% by mass) Formula 9 Formula 10 Formula 11 2 phenoxy-ethylacrylate (2PEA) 11.3% 11.9% 11.8% phenoxy-ethyl methacrylate (MAPE) 34.8% 29.5% 29.5% 4-hydroxy-butyl-acrylate (4HBA) 29.5% 34.4% 34.5% ethoxy-ethyl methacrylate (MAEE) 18% 17.8% 16.3% triethylene glycol dimethacrylate 4.4% 4.4% 5.9% cinnamic alcohol 0.5% 0.5% 0.5% anti-UV compound 1.5% 1.5% 1.5%

[0117] For each of the formulas of the examples, the polymerization reaction was triggered by the addition of 1.5% of TAEC and 1.5% of dicumyl peroxide.

[0118] After polymerization at 120°C for a period of 3 hours, acrylic polymer materials were obtained having, in the ambient dry state, an optical index respectively equal to 1.522 for formula 1, 1.531 for formula 2, 1.522 for formula 3, 1.523 for formula 4, 1.527 for formula 5, 1.528 for formula 6, 1.529 for formula 7, 1.529 for formula 8, 1.526 for formula 9, 1.524 for formula 10 and 1.527 for formula 11.

[0119] After cooling, demolding and purification, intraocular lenses, with a vergence of 20 D, were machined from the polymer material discs obtained with these different formulas.

[0120] The vergence of an intraocular lens is a parameter well known to those skilled in the art, expressed in diopters (D), which reflects the thickness in the curved central part of the lens and is easily calculated from the thickness of the mold used.

[0121] Intraocular lenses of 20D vergence were also obtained by direct molding from formulas 5 to 11, by placing these monomer mixtures to carry out the polymerization in molds of a shape corresponding to the final lens targeted and of a material compatible with the polymerization temperature. In this way, after cooling, demolding and purification, intraocular lenses are obtained which do not need to be machined.

[0122] For this purpose, a mixture of TAEC and tert-butyl peroxy-2-ethylhexanoate (CAS 3006-82-4) was used as initiator compounds instead of the mixture of TAEC and dicumyl peroxide, in order to lower the polymerization temperature. With such peroxides, the polymerization temperature can be kept below 100°C, which ensures that the polypropylene molds do not deform. used.

[0123] In order to demonstrate the surprising and particularly advantageous properties of the polymer materials according to the invention, the elastic moduli of several formulas above were measured under different conditions: at 20°C in the ambient dry state, at 35°C in the hydrated state and at 65°C in the hydrated state. The measured values ​​were compared with the elastic moduli of the prior art material marketed under the name ENVISTA™ measured under the same conditions.

[0124] The measurements in the ambient dry state at 20°C were carried out with dry materials in equilibrium with the quantity of humidity present in the air at 20°C, under normal ambient conditions of humidity and pressure.

[0125] The measurements at 35°C or 65°C in the hydrated state of the materials were carried out with materials which were immersed in water at 35°C for a period of 48 hours before carrying out the measurement.

[0126] The material sample to be tested is then placed in the measuring device where its temperature is kept at 35°C or brought to 65°C. All elastic moduli were measured at a frequency of 1Hz in accordance with ISO 6721-1.

[0127] The measured data have been grouped in the table below.

[0128] [Tables4] Material tested Modulus of elasticity in MPa, dry ambient at 20°C Modulus of elasticity in MPa, hydrated at 35°C Modulus of elasticity in MPa, hydrated at 65°C ENVISTA™ 282.71 8.27 1.10 Formula 5 35.11 1.3 0.55 Formula 6 42.51 1.5 0.97 Formula 8 87.24 1.47 1.08 Formula 9 85.45 1.78 1.11 Formula 10 47.43 1.5 1.16 Formula 11 81.78 1.83 1.62

[0129] On reading these results, it can be seen that the moduli of elasticity at 20°C in the ambient dry state of the formulas according to the invention tested are significantly lower than that of the ENVISTA™ material of the prior art measured under the same conditions.

[0130] Under these conditions, which correspond substantially to those of an operating room, all the materials in accordance with the invention tested have a modulus of between 30 and 90 Mpa. In the ambient dry state, they can therefore be rolled without difficulty and placed in an injector without deteriorating. They can then be injected into the eye of a patient without the pushing force required to eject them from the injector being too great, for example greater than 20 N. The surgeon can therefore easily and comfortably implant an intraocular lens made from these materials in a dry ambient state under operating room conditions.

[0131] On the contrary, with a modulus of elasticity greater than 280 MPa, the prior art ENVISTA™ material is extremely rigid in the ambient dry state. It is impossible to roll an intraocular lens made from this material in the ambient dry state to place it in an injector without risking damage. Furthermore, it would also not be possible to inject it manually into a patient's eye, as the necessary pushing force is far too great.

[0132] In order to be implanted, intraocular lenses made from ENVISTA™ material must therefore be hydrated to lower their modulus of elasticity, this material having a modulus of elasticity of 42.75 MPa in the hydrated state at 20°C. This requires them to be packaged and stored in an aqueous medium, which has numerous drawbacks as explained in the introduction.

[0133] In the hydrated state at 35°C, which corresponds to conditions close to those encountered in a human eye, the elastic moduli measured for the materials according to the invention tested are between 1.3 and 1.83 Mpa. They are therefore slightly lower than that of the ENVISTA™ material which is equal to 8.27 Mpa under the same conditions, but with a comparable order of magnitude resulting in similar behavior. In addition, all the materials according to the invention tested have an elastic modulus greater than 1 in the hydrated state at 35°C which guarantees satisfactory hold of the lens once implanted and ensures firm centering inside the crystalline sac.

[0134] The values ​​of the elastic moduli were also measured in the hydrated state at 65°C, in order to simulate the behavior of these materials after a long time under the conditions of a human eye. Indeed, in application of the principle of time-temperature equivalence and the Williams-Landel-Ferry law well known to those skilled in the art, the value of the elastic modulus of a plastic material measured at 65°C and 1 Hz corresponds substantially to the value of the modulus of this material measured at 35°C after more than 277 hours under constant stress. This measurement of the moduli in the hydrated state at 65°C under 1 Hz therefore makes it possible to evaluate the long-term behavior of intraocular lenses implanted in the eye of a patient and thus to simulate their aging.

[0135] As can be seen from the table, all the materials according to the invention tested have a modulus of elasticity, measured in the hydrated state at 65°C and 1 Hz, between 0.55 and 1.62 Mpa and for most of them close to 1 to 1.15 Mpa. These values ​​correspond approximately to that of 1.10 MPa measured for the ENVISTA™ material under the same conditions. The materials according to the invention tested therefore have a long-term behavior similar to that of the prior art ENVISTA™ material. Furthermore, although the moduli measured at 65°C have slightly decreased compared to those measured at 35°C, these remain of the same order and are sufficient to ensure the lens is held in position and centered satisfactorily in the crystalline bag.

Claims

Claims

1. Acrylic polymer material, suitable for the production of intraocular lenses, characterized in that it is a crosslinked copolymer, prepared from a mixture of monomers containing at least: - 2-phenoxyethyl acrylate (2PEA) and / or 2-phenoxy-(2-ethoxy)4-acrylate (4PEA); - phenoxyethyl methacrylate (MAPE) and / or benzyl methacrylate; - a hydroxylated acrylate and / or a hydroxylated methacrylate, the glass transition temperature (Tg) of which is less than 20°C, preferably less than 15°C and even more preferably less than 10°C; - ethoxyethyl methacrylate (MAEE); and - a polyethylene glycol diacrylate comprising 3 to 5 ethoxyl functions and / or a polyethylene glycol dimethacrylate comprising 3 to 5 ethoxyl functions.

2. Acrylic polymer material according to claim 1 characterized in that the mixture of monomers comprises at least 80%, preferably at least 90%, by mass of acrylic and / or methacrylate monomers.

3. Acrylic polymer material according to claim 1 or 2 characterized in that the 2-phenoxy-ethyl acrylate (2PEA) and / or the 2-phenoxy-(2-ethoxy)4-acrylate (4PEA) represents between 7 and 36%, preferably between 10 and 20% and more preferably between 11 and 15% by mass of the monomer mixture.

4. Acrylic polymer material according to any one of the preceding claims, characterized in that the phenoxyethyl methacrylate (MAPE) and / or the benzyl methacrylate represents between 15 and 45%, preferably between 25 and 40% and more preferably between 29 and 35% by mass of the mixture of monomers.

5. An acrylic polymer material according to any one of the preceding claims characterized in that the hydroxylated acrylate is 4-hydroxy-butyl acrylate (4HBA) or hydroxy-hexyl acrylate.

6. Acrylic polymer material according to any one of the preceding claims, characterized in that the hydroxylated methacrylate is a polyethylene glycol monomethacrylate comprising one to three ethoxyl functions or butanediol monomethacrylate.

7. Acrylic polymer material according to any one of the preceding claims, characterized in that the hydroxylated acrylate and / or the hydroxylated methacrylate represents between 20 and 40%, preferably between 25 and 35% and more preferably between 28 and 35% by mass of the mixture of monomers.

8. Acrylic polymer material according to any one of the preceding claims, characterized in that the ethoxyethyl methacrylate (EMAE) represents between 5 and 30%, preferably between 10 and 25% and more preferably between 15 and 20% by mass of the mixture of monomers.

9. Acrylic polymer material according to any one of the preceding claims, characterized in that the polyethylene glycol diacrylate comprising from 3 to 5 ethoxyl functions is triethylene glycol diacrylate, and in that the polyethylene glycol dimethacrylate comprising from 3 to 5 ethoxyl functions is triethylene glycol dimethacrylate.

10. Acrylic polymer material according to any one of the preceding claims, characterized in that the polyethylene glycol diacrylate comprising from 3 to 5 ethoxyl functions and / or the polyethylene glycol dimethacrylate comprising from 3 to 5 ethoxyl functions represents between 3 and 6% and preferably between 3.5 and 6% by mass of the mixture of monomers.

11. Acrylic polymer material according to any one of the preceding claims, characterized in that the mixture of monomers further comprises one or more polyethylene glycol dimethacrylates comprising from 10 to 30 ethoxyl functions.

12. Acrylic polymer material according to claim 11 characterized in that the polyethylene glycol dimethacrylate(s) comprising from 10 to 30 ethoxyl functions represents up to 2% and preferably up to 1% by mass of the monomer mixture.

13. Acrylic polymer material according to any one of the preceding claims, characterized in that the monomer mixture further comprises cinnamic alcohol or a transfer agent; preferably cinnamic alcohol in an amount of between 0.1% and 5%, more preferably between 0.2% and 2% by mass of the monomer mixture and even more preferably in an amount representing approximately 0.5% by mass of the monomer mixture.

14. An acrylic polymer material according to any one of the preceding claims characterized in that the monomer mixture comprises furthermore a UV absorbing monomer, preferably in an amount of between 0.1 and 2% by mass of the monomer mixture and more preferably in an amount representing approximately 1.5% by mass of the monomer mixture.

15. Process for manufacturing an acrylic polymer material according to any one of claims 1 to 14, characterized in that it comprises the following steps: . we produce a mixture of monomers containing at least: - 2-phenoxyethyl acrylate (2PEA) and / or 2-phenoxy-(2-ethoxy)4-acrylate (4PEA); - phenoxyethyl methacrylate (MAPE) and / or benzyl methacrylate; - a hydroxylated acrylate and / or a hydroxylated methacrylate, the glass transition temperature (Tg) of which is less than 20°C, preferably less than 15°C and even more preferably less than 10°C; - ethoxyethyl methacrylate (EMAE); and - a polyethylene glycol diacrylate comprising 3 to 5 ethoxyl functions and / or a polyethylene glycol dimethacrylate comprising 3 to 5 ethoxyl functions; . at least one initiator compound is added to said mixture; . the said mixture is polymerized by radical means, in a single polymerization step, so as to obtain by this polymerization a crosslinked copolymer.

16. Intraocular lens characterized in that it is made of an acrylic polymer material according to any one of claims 1 to 14.

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