Optical system, in particular intraocular lens, contact lens

OPTICAL SYSTEM, ESPECIALLY INTRAOCULAR LENS, CONTACT LENS

The present invention relates to optical systems, in particular centered optical systems such as intraocular lenses, contact lenses, etc.

We know that the human eye is a complex optical system whose role is to transmit the images that reach it to the brain. One of the essential elements is the lens. Located behind the iris, the lens is a transparent gelatinous mass contained in the lens sac.

Clouding of the lens can occur with age (cataracts). We are then forced to remove the deficient lens and replace it with an artificial lens or an intraocular lens.

The artificial crystalline lenses known to date are essentially made of acrylic materials, for example polymethyl-methacrylate or its copolymers, or of silicone derivatives. They have relatively low refractive indices. For silicones, we currently have refractive indices of between 1.41 and 1.46 at best. For strong corrections, it is therefore necessary to use intraocular lenses whose faces have a significant curvature and which, therefore, have a great thickness at their optical axis.

To obtain the best correction and not to induce astigmatism defects, it is also necessary to introduce the intraocular lens through an incision of the smallest possible dimension. To do this, we are looking for flexible materials and the greatest possible refractive index so as to obtain a very fine intraocular lens.

The healthy eye has a crystalline lens capable, under the action of muscles, the zonules, which mobilize the lens sac, of modifying its radius of curvature so as to adapt to near vision or vision. from afar.

Replacing the lens with an intraocular lens no longer allows accommodation.

One of the objectives of the present invention is to provide an optical system of the intraocular lens type which overcomes the drawbacks of those of the prior art.

More precisely, the present invention relates to an optical system, in particular intraocular lens, contact lens, characterized in that it is made of a material whose optical refractive index exhibits variations in at least one given direction.

According to one characteristic of the invention, said material is a homogeneous material whose refractive index is variable depending on its chemical composition.

According to another characteristic of the invention, said material is a material i

heterogeneous with variable molecular orientations according to different areas.

According to another characteristic of the invention, said material is a homogeneous material capable of modifying its optical refractive index when it is subjected to the action of external phenomena.

Another application is the production of bifocal contact lenses, allowing simultaneous correction of two visual defects (myopia and presbyopia for example):

- or by juxtaposition of two materials, a central, a peripheral, of a similar nature, but of different indices, thanks to different grafting rates on the same matrix;

- or by juxtaposition of two different domains of the same material, the two domains having different refractive indices thanks to a molecular orientation;

- or by making a material whose index varies under the effect of a mechanical stress, the pressure of the eyelids for example.

Other characteristics and advantages of the present invention will become apparent from the following description given with reference to the accompanying drawings by way of illustration, but in no way limiting, in which:

FIGS. 1 and 2 represent graphs making it possible to explain the variations in the properties of materials used for producing the optical system of the intraocular lens type according to the invention as a function of the composition of these materials, the graph according to FIG. 1 representing the '' change in glass transition temperatures as a function of the level of substituents, and the graph according to FIG. 2 representing the change in the refractive index n as a function of the level of substituents.

The optical system of the intraocular lens type according to the invention is made of a material whose optical refractive index exhibits variations in at least one given direction.

In a first embodiment, this material is homogeneous and has a high refractive index n which varies according to its chemical composition.

Indeed, for a given molecule, the molar refraction R is, as a first approximation, an additive function of the contributions of the various elements present in the molecule. Among the common chemical groups, those which have the most important effects in increasing R are mainly sulfur, halogens, especially chlorine, bromine and iodine, and aromatic rings.

The refractive index n of the molecule increases with R so that it is the molecules containing the elements mentioned above which have the highest indices.

Examples: benzene n = 1.498 o-dichlorobenzene n = 1.551 carbon disulfide n = 1.628 diiodomethane n = 1.749

Likewise, the addition of groups of high refractive index n to a polymer increases the refractive index of the material.

By way of example, mention will be made of the case of silicones substituted with 9-vinyl anthracene entities. The refractive index of the material obtained increases with the rate of substituents:

- without substituent: n = 1.403

- with 94% of substituents: n = 1.690

The glass transition temperatures Tg also increase with the degree of substitution due to the rigidity of the aromatic rings:

- without substituent: Tg = - 130 ° C

- with 94% of substituents: Tg = between 10 ° C and 20 ° C

The process for manufacturing the material which is homogeneous and exhibiting a high refractive index n and variable according to its chemical composition, necessary for the production of an intraocular lens according to the invention comprises the following two steps:

First, groups chosen from those described above, in particular aromatic rings, the presence of which also confers on the material obtained a capacity for filtering ultraviolet radiation, an essential property for a good quality intraocular lens, are attached to the polymers. used for lenses and artificial crystals, this fixing being obtained by means of a flexible part in order to disturb the temperature Tg as little as possible.

Examples: Substitute of type [1]:

<img file="FR2777091A1_D0001.tif" />

Substitute type [2]:

(CH₂)_not

O

<img file="FR2777091A1_D0002.tif" />

with Z = OCO, COO, -, ...

Y = H, OCmH2m + L CmH2m + L - with n&gt; 2, m&gt; l, x = l, 2, 3, ...

I

<img file="FR2777091A1_D0003.tif" />

Then, the degree of substitution is continuously modified, and therefore also the refractive index of the material, to obtain copolymers with an adjustable proportion of substituted units and of unsubstituted units. In the case of silicones, it is necessary to prepare the copoly (methylhydrogen-dimethyl) siloxane of variable composition beforehand.

Two examples are given below, one from a silicone support, the other from an acrylate support, the substituent chosen corresponding to formula [1] above where n = 4, Z = OCO, Y = OCmH2m + l with m = l, x = l.

In the case of the first example, that with a silicone support, the substituent must have a terminal vinyl bond:

Example: CH2 = CH (CH2) 2 O OCO

This group can be obtained in two stages: reaction of 4-bromobutene with hydroquinone, then esterification with p-methoxybenzoic acid.

The main siloxane chain has a statistical distribution of substitutable methylhydrogenosiloxane units and non-substitutable dimethylsiloxane units in varying proportions. These copolymers are obtained by acid-catalyzed redistribution of dimethylsiloxane units introduced in an adequate amount via octamethylcyclotetrasiloxane and of methylhydrogenosiloxane units supplied by homopolymethyl-hydrogenosiloxanes.

The substituent is attached to the main chain by hydrosilylation at 60 ° C. in the presence of a solvent. It is introduced in default with respect to the methylhydrogen enosiloxane units (from 5% to 15%) in order to allow a subsequent reaction of the excess units during the crosslinking step.

At the end of the hydrosilylation reaction, the polymer is freed from almost all of the solvent by evaporation under vacuum at room temperature. It is then mixed with a crosslinking agent, and the remainder of the solvent is evaporated off in vacuo.

The crosslinking agent is preferably a flexible chain and ends with two vinyl ends. Its proportion is such that the quantity of vinyl bonds corresponds to the quantity of methylhydrogenosiloxane units left free.

Example of crosslinking agent: CH2 = CH (CH2) pCH = CH2 p = 2 to 20

CH2 = CH (Si (CH3) 2O)_qCH = CH2 q = 2 to 10

The polymer / crosslinking agent mixture is poured into a mold treated so that the material does not stick to the walls. The mold is placed at 60 ° C. in an oven for several hours in order to obtain a crosslinked polymer which is demolded.

This product can be washed by swelling it with a solvent, in order to eliminate any molecules which have not reacted, then by drying it slowly.

In the second example, that with an acrylate support, the acrylate or methacrylate monomer, carrying the chosen substituent, must be synthesized:

Example: CH2 = CX COO (CH2) 4 O

<img file="FR2777091A1_D0004.tif" />

<img file="FR2777091A1_D0005.tif" />

OCH3 with X = H, CH3

This group can be obtained in four stages: reaction of 4-bromobutanol, in which the alcohol function has been protected, with hydroquinone; esterification with pIQ methoxybenzoic acid; deprotection of the alcohol function; esterification between this alcohol function and the carboxylic group of acrylic or methacrylic acid.

A difunctional monomer having an acrylate or methacrylate function at both ends must also be synthesized. Π can be obtained according to the following scheme: reaction of 4-bromobutanol in which the alcohol function has been protected, with hydroxybenzoic acid; esterification by the reaction product of 4-bromobutanol in which the alcohol function has been protected, on hydroquinone; deprotection of alcohol functions; esterification of these alcohol functions by the carboxylic functions of acrylic or methacrylic acid.

Other difunctional monomers can be used: ethylene glycol 2q dimethacrylate; triethylene glycol dimethacrylate; tetraethylene glycol dimethacrylate; 1.6 hexane diol dimethacrylate; 1.12 dodecane diol dimethacrylate.

The polymerization is triggered by heating or UV irradiation in the presence of an initiator (azobis isobutyronitrile for example) or by any other common system (chemical accelerator, microwave irradiation).

Obtaining crosslinked materials of variable proportion of substituents is possible by mixing, prior to the polymerization reaction, one or more unsubstituted monomers (methyl acrylate, methyl methacrylate, hydroxy ethyl methacrylate for example) with the above monofunctional monomers and bifunctional in adequate proportion. Hydroxy ethyl methacrylate (HEMA) brings a hydrophilic character to the material until a degree of hydration of 40% is obtained for a homopolymer. It is also possible to combine it with even more hydrophilic comonomers such as N-vinyl pyrrolidone (VP) for example.

The crystalline lenses or lenses can be obtained either by machining the final materials or by carrying out the last step (polymerization / crosslinking) in a mold. In the case where the base monomer has hydrophilic qualities, the final material can be swollen in an aqueous medium and become more or less pliable depending on its composition.

i

I

The materials thus obtained exhibit, with respect to the basic silicones or acrylates, properties which allow the production of artificial crystalline lenses, intraocular lenses, or contact lenses according to the invention.

Indeed, their refractive index n and their glass transition temperature Tg are higher and vary according to their chemical composition. In particular, they increase with the increase in the proportions of the substituents.

An example of this development is illustrated in FIGS. 1 and 2 for silicone materials, the method of synthesis of which has been given above.

In this example, the crosslinking agent is an alkyl chain; three chain lengths of crosslinking agent were studied corresponding to 10, 16 or 22 carbons; three different proportions of this crosslinking agent were introduced (5, 10, 15%). These two parameters have little influence on the evolution of the refractive index or the glass transition temperature, as can be seen in Figures 1 and 2.

On the other hand, the refractive index increases very rapidly with the rate of substituents, FIG. 2, since with 40% of substituents one obtains indices greater than 1.53.

The change in the glass transition temperature, Figure 1, is slower. Even with full substitution, Tg remains below room temperature.

The mechanical properties are relatively little disturbed by the substituents. For example: the elastic modulus under shear (G ') at zero frequency: unmodified silicone: G' = 10 ^ Pa silicone with more than 85% of substituents: G '= 4.10 ^ p_To

According to a second embodiment, the material in which the intraocular lens according to the invention is made is a heterogeneous material of high index and variable in the material.

The aromatic substituents proposed above are thermotropic liquid crystals. They provide mesomorphic properties to the polymer which carries them, that is to say in particular properties of molecular orientation: in a given temperature range, these substituents orient themselves very easily under the effect for example of a magnetic field or electric. This orientation is then fixed by the crosslinking process.

Under the effect of the orientation as mentioned above, the refractive index becomes anisotropic. Π is therefore possible, by orientation of the substituents, to modify the refractive index in a given direction.

According to the present invention, the optical system is obtained from the same polymer, silicone or acrylate or methacrylate for example, by producing batches of different indices obtained by orientations of the substituents in different directions.

The orientations can be obtained by placing the substituted polymer (in the case of silicones) or the various monomers, substituted or not, (in the case of acrylates) in a weak magnetic field of about 1 Tesla or in an electric field, or by a surface treatment of the device making it possible to manufacture the material or the lens in its final form. The crosslinking (in the case of silicones) or the polymerization / crosslinking (in the case of acrylates) are carried out by heat treatment, for example, under this orienting field.

These batches of the same chemical nature are perfectly compatible. They can be assembled so as to form lenses or crystalline lenses with different accommodation zones. For example, an intraocular lens could be produced in two parts: a central optical zone suitable for near vision and a peripheral zone suitable for far vision.

According to a third embodiment, the material used for making the optical system of the intraocular lens type according to the invention is a homogeneous material with a high index and variable by mechanical effect, thereby allowing accommodation.

According to one characteristic of the invention, the material in which the optical system is made is a three-dimensional liquid crystal polymer whose orientation of the mesomorphic entities can easily be obtained by mechanical effect.

Crosslinked liquid crystal polymers can for example first be produced without prior orientation of the mesogens. From this material, will then be produced, for example by polymerization / crosslinking in a mold or by machining according to the properties of the material, artificial crystals or intraocular lenses. Zonules exert a mechanical stress which is reflected, through the lens sac, on the lens. This constraint modifies the orientation of the liquid crystal substituents and therefore the refractive index in the viewing direction. Likewise in the case of contact lenses, pressure on the eyelids can give rise to the mechanical deformations necessary for molecular reorientation and therefore vary the refractive index and on the other hand the power of the lens.

It is also possible to give these materials during their production, a prior orientation of the substituents, which will be modified under the effect of compressions or stretches transmitted to the bag by the zonules.

In order for the material without prior orientation of the mesogens to be transparent, or for a previously oriented material to remain transparent after disorientation, it is placed in the isotropic phase under the conditions of use. In addition, to obtain a sufficient orientation under stress and therefore a significant modification of the refractive index, it is necessary to carry out the process in a temperature range of approximately 10 ° C above the temperature Tj to which the sample becomes isotropic.

This obligation imposes an upper limit on the substitution rate as illustrated in Figure 1. In the example chosen, a siloxane modified at around 35% would be perfectly suitable: it is isotropic at around 35 ° C with a refractive index greater than 1.51. (Figure 1).

In isotropic phase, the index variation is all the more important as the temperature of use is close to Ή. An example of the index difference between two perpendicular directions, Δη, induced by a mechanical stress is given below. The compound chosen corresponds to a methacrylate substituted by various groups of the type [2] defined above:

toTi + 4

0

VS, Δη = 6.10

-

^ for a stress of 5.10'2 N.mm'2 Δη = 2.10'3 for a stress of 2.10'2 N.mm'2 atTI + 25 ° C, Δη = 1.10'3 for a stress of 5.10'2 N.mm'2 Δη = 0.3.10'3 for a stress of 2.10'2 N.mm'2