FR2655270A1 - Intraocular lens made from hydrogel, having shape memory - Google Patents

Abstract

Intraocular lens made from hydrogel, having shape memory, swelling in water or in an isotonic solution such as physiological saline, which is deformed before implantation in an appropriate shape for for the purpose of surgical introduction, for example, in the form of a rod, produced, at least partially, from a cross-linked synthetic hydrogel containing acidic and/or basic groups.

Description

 The present invention relates to a hydrogel intraocular lens provided with shape memory swelling in water or in an isotonic solution, such as physiological saline, which is deformed before implantation into an appropriate shape for surgical introduction, for example in the form of a rod, and is intended for introduction inside the eye into the anterior or posterior chamber or behind the horn.

 Hitherto known intraocular lenses are mainly in a definitive form and physical state before their surgical introduction into the eye.

These lenses are made either of hard polymer, such as polymers of methacrylic acid esters or of acrylic acid with lower aliphatic alcohols, for example, methyl methacrylate (MMA), or in flexible hydrogels swollen with balance in physiological saline before introduction into the eye. A relatively long incision is required in both cases in order to slide the lens into position. Hard lenses cannot be deformed at an applicable temperature to facilitate insertion.With common hydrogel lenses made of slightly cross-linked polymers, such as hydroxyethyl methacrylate (HEMA) polymer, possible temporary deformation is limited, if not impossible , due to their elasticity and their tendency to break for too sudden bending In addition, hard lenses increase the risk of injury to sensitive eye tissue during their placement.

 Recently an intraocular lens has appeared which is deformed before and during the operation in the form suitable for surgical introduction, thus making it possible to shorten the incision (US Patent No. 4,731,079, Czechoslovak Patent Application 9596-86). The lens takes its final form only in the eye in the position provided for it.

 The voluntary deformation is, for example, a winding or compression of the lens into a narrow rod or, at least, its folding or its single or multiple winding in order to reduce the necessary length of 1 incision at least by half.

 After surgical introduction, which is considerably facilitated by this deformation, the lens relaxes in the eye by heating to the temperature of the eye and thus takes the desired shape, elasticity and initial flexibility. The deployment speed is predetermined and the surgeon must operate very quickly and skillfully without making any mistakes.

 According to the aforementioned documents, the lens is / either not swollen at equilibrium and undergoes subsequent swelling in the eye (Czechoslovakian patent application 959686), or is swollen at equilibrium with a low water content (up to 20 %) and the water content does not vary in the eye (US Patent No. 4,731,079).

 One of the aims of the present invention is an intraocular lens provided with shape in water or in an isotonic solution, such as physiological saline, which is deformed before implantation in the form of a rod (for example, according to the Czechoslovak patent application 9596-86), and produced in a crosslinked synthetic hydrogel containing acid and / or basic groups.

 The acidic and / or basic groups may be present in the entire mass of the lens or in the surface layer of the lens from 1 to 200 μm thick or only in a part of the lens.

This depends on the application required (deployment speed, secondary deformation).

 The acid groups which are used according to the invention are present, for example, in sulfoalkyl (meth) acrylate, sulfoal # yl (meth) acrylamide, (meth) acrylic acid, and other types.

 The basic groups which are used according to the invention are present, for example, in aminoalkyl (meth) acrylate, aminoalkyl (meth) acrylamide, vinylpyridine compounds, their quaternary ammonium salts, and other types.

 For the manufacture of intraocular lenses, copolymers containing acid and / or basic groups in the form of acids and bases may be used (for example, copolymers of 2-hydroxyethyl methacrylate - methyl methacrylate - acid (meth ) acrylic, 2-hydroxyethyl methacrylate - (meth) acrylic acid and others) or copolymers containing these acid or basic groups in the form of salts and are additionally transferred in acid or basic form by modifying the pH (for example, copolymers of 2-hydroxyethyl methacrylate - potassium or sodium methacrylate, 2-hydroxyethyl methacrylate - methyl methacrylate- sodium or potassium methacrylate.

 The acid or basic groups can also be created by a reaction analogous to a polymerization of certain polymers, for example, by acid or alkaline hydrolysis.

 There is no difference in this case that only acid groups or only basic groups are present in the polymer or that both acid and basic groups are present simultaneously.

 The lens according to the present invention uses the variation of water content in a hydrogel according to the pH and the ionic cohesion of the medium. Hydrogels containing acidic and / or basic groups modify their water content according to ionic cohesion and pH (depending on the pH of the acid or the base). This phenomenon is caused by the degree of dissociation of acidic or basic groups.

For example, the dissociation constant for iaethacrylic acid is 5.1, which means that the swelling of the hydrogel increases sharply if the pH is greater than 5.

 Because the ionic cohesion of liquid bodies is constant and the pH ranges between 7.0 and 7.2, copolymers can be prepared which are elastic under these conditions and become hard to a lower (acid) or higher value (bases) of the pH. In particular, crosslinked copolymers and terpolymers of acrylic acid or methacrylic acid with methyl methacrylate or 2-hydroxyethyl methacrylate are concerned.

 After heating of such a polymer above Tg, its deformation and its cooling, the polymer remains in the deformed state until the ionic cohesion or the pH of the surrounding medium is modified.

 The equilibrium swelling of the lens according to the invention is lower in the acid or basic cycle than the equilibrium swelling after neutralization of acid or basic groups.

 The more ionogenic groups in the polymer, the greater the difference between the equilibrium swelling in the acid or basic form and the equilibrium swelling in the neutralized form.

 It is possible to use the increased swelling ability of the lenses in the form of salts in water in comparison with the saline solution. Lenses are thus obtained which, after implantation, are unfolded and then deflate and harden.

 A successive double deformation can also be obtained with the intraocular lens endowed with shape memory according to the invention, according to the pH and the ionic cohesion. We start from a lens whose acid or basic groups are transferred in the form of a salt.

Then part of the lens, advantageously its posterior side, that is to say the side which is turned towards the inside of the eye after implantation, is transferred in the acid or basic cycle, while the other part of the lens remains in the form of a salt. This can be obtained by local action of solutions of strong acids or bases or by their electrolytic formation.

 The water content is adapted and the lens is then deformed and cooled (for example according to Czechoslovak patent application 9596-86). After introducing this deformed lens into the eye, the lens is deployed under the effect of temperature, but is curved due to an uneven swelling of its parts (the lower part swells less, the upper part swells more) so that it can be easily slid through the pupil into the posterior chamber where the part occurring in the acid or basic cycle (i.e. the lower part in this case) is again transferred under the salt form (as is the case with the other part of the lens) thanks to the damping capacity of liquid bodies.

 Different deformations can be obtained in this way with the lens according to the invention as a result of the different swelling in the acid or basic form and in the neutralized form.

 Any suitable method can be used to shape the intraocular lens according to the invention, for example, rotational molding with polymerization or copolymerization and / or crosslinking carried out simultaneously, or turning from a xerogel, or pressing, or a injection molding, and other processes.

 The non-crosslinked lenses can be further crosslinked, for example, by irradiation or additional introduction of a crosslinking agent and heating in the presence or absence of an appropriate polymerization initiator. For injection molding, suitable solutions of the polymer can also be used in a suitable water-miscible solvent, which is washed away. The deformed lens, after surgical introduction into the eye, swells subsequently and relaxes immediately, for example in a few seconds or minutes, as a result of the change in pH. The lens acquires by loosening its initial shape, its elasticity and its flexibility.

 The invention is explained below using a real example.

Example
A mixture of 35% by weight of methyl methacrylate, 60% by weight of 2-hydroxyethyl methacrylate, and 5% by weight of methacrylic acid containing 0.05% of diisopropyl peroxocarbonate is charged in an ampoule.

The mixture is then bubbled with argon and the bulb is sealed and heated at 400C for 12 hours, at 600C for 24 hours, and at 800C for 24 hours.

The bulb is broken and a polymer plug is removed.

An intraocular lens is turned from the stopper, polished, and allowed to swell in an isotonic solution of NaHCO3. The equilibrium swelling of the lens is 24% by weight. The lens is washed in physiological saline, pressed in the inflated state by its lower face on a filter paper soaked in a 1 M HCL solution, and left in this position for 5 minutes. It is then again washed with physiological saline. The lens is deflated at the point of contact and bent. In this state, it is sterilized in an autoclave. Before implantation, it is heated to 500C and deformed in deformation equipment to take the form of a rod, cooled to 150C and introduced through an incision of 3.5nom into the inner chamber of the eye. The lens deploys in approximately 30 seconds, but its support parts remain curved so that the lens can be easily slid through the pupil into the posterior chamber of the eye where it is straightened in stages under the effect of the stable pH of the mood of the room. This process takes approximately 5-8 minutes.

Claims (4)

1. Intraocular hydrogel lens, with shape memory swelling in water or in an isotonic solution, such as physiological saline, which is deformed before implantation into a form suitable for surgical introduction, for example in the form of 'a rod, in which the lens is made, at least in part, of a crosslinked synthetic hydrogel containing acid and / or basic groups.  2. Intraocular hydrogel lens according to claim 1, in which the acid and / or basic groups are found in the surface layer of the lens from 1 to 200 µm thick. 3. Intraocular hydrogel lens according to claims 1 and 2, in which the acid and / or basic groups are located on the lower part of the lens which is, after implantation, turned towards the interior of the eye. 4. Intraocular hydrogel lens according to claim 1, wherein the lens, after implantation, deflates and hardens.