Capable of hydration of the copolymer (options), ophthalmic device, a method of manufacturing an intraocular lens, the method of implantation ophthalmic device in the eye

 

(57) Abstract:

This invention relates to a copolymer materials used as ophthalmic devices such as contact lenses, intraocular lens (IOL), keratoplasty and corneal rings or inserts, in particular, to a soft intraocular lenses made of acrylic copolymer material, and the method of production and use of such polymeric materials. Described is capable of hydration of the copolymer containing three Monomeric component. The first Monomeric component includes arylaryl or allmaterial. The second Monomeric component, non-acrylate, contains a monomer having an aromatic ring with substituent having at least one unsaturated ethylene fragment. The third Monomeric component includes a monomer capable of forming hydrogels with high water content. The copolymer receive as a result of the polymerization reaction of the first, second and third Monomeric component and a crosslinking agent. Also described ophthalmological device, capable of containing the hydration of the copolymer, a method of manufacturing an intraocular lens and method of implantation ophthalmic device is carried out in dry hard enough, so it can be cutting and polishing, and becomes soft and flexible when hydration. 6 N. and 36 C.p. f-crystals, 3 tables.

This invention relates to a copolymer materials used as ophthalmic devices such as contact lenses, intraocular lens (IOL), keratoplasty and corneal rings or inserts, as well as the method of production and use of such polymeric materials. In particular, this invention relates to a soft intraocular lenses made of acrylic copolymer materials.

In light of the latest advances in cataract surgery using the technique of small incisions, special attention was paid to the development of soft flexible materials suitable for use in an artificial eye lenses. Generally speaking, these materials belong to one of three categories: hydrogels, silicones and all the rest.

The power of the lens depends on its shape and refractive index of the substance from which it is made. Lens made from a material with a high refractive index, can be thinner and still have the same optical power as the lens is made of a material with a lower coefficient pre the tx2">Dry hydrogels are solid or tugamadimi, and when the hydration they absorb large amounts of water (for example, up to 20-70% by weight), which reduces the refractive index of the material. These materials tend to break during drying and are poor for use in ophthalmology mechanical properties. In the hydrated state materials based hydrogels are soft and flexible. Known hydrated hydrogels have a relatively low refractive index, for example less than 1.48. In addition to adverse effects on the refractive index, the absorbed water also increases the diameter and thickness of the intraocular lens, for example, the value of up to about 15 percent.

Silicone materials have a slightly higher refractive index (for example, 1.51), but tend to go too quickly when injected into the eye in a folded condition. Characteristics of biocompatibility of silicone materials are also of concern.

In U.S. patent No. 5290892 (Namdaran and others), 5331073 (Weinschenk, III, and others) and 5693095 (Freeman and others) discussed the formation of soft lenses made of polymeric material obtained from ethoxyacrylate with the crosslinker or with others who baggetta forming polymeric material in the forms for individual lenses. Similarly, in U.S. patent No. 5433746 name Namdaran, etc. discussed getting soft intraocular lenses by molding polymeric materials having a relatively low glass transition temperature. This formation requires special equipment and expensive custom-made forms. In addition, the resulting molded lenses usually show poor surface quality, because usually they cannot be polished. Alternatively, in U.S. patent No. 5331073 discussed forming lenses of soft/flexible material by means of mechanical processing of lenses at cryogenic temperatures. This process is very cumbersome and expensive.

Create a soft (flexible) material with a high refractive index, which can be machined and polished using conventional technology would be a significant achievement in this field of technology.

The INVENTION

This task is solved by the present invention is the creation of a flexible material with a high refractive index, which can be machined and polished using conventional inexpensive ways of cutting on lathes, such as those of caloriewise ophthalmic devices, in particular intraocular lenses contain polymer chains consisting of at least three different Monomeric components. The resulting polymeric materials are also suitable for other ophthalmic devices such as contact lenses, keratoplasty, intraocular lens (IOL) and corneal rings or pads, and other products.

Capable of hydration of the copolymer according to the invention contains:

a) a first Monomeric component containing arylaryl or allmaterial;

b) a second Monomeric component containing a monomer having an aromatic ring with the Deputy, at least one unsaturated ethylene fragment, and the second Monomeric component is an acrylate;

C) a third Monomeric component containing a monomer capable of forming hydrogels with high water content.

This copolymer, when hydration is flexible, and when hydration sizes copolymer preferably increases by less than 10 volume percent, compared with an UN-hydrated copolymer.

This copolymer, when hydration is flexible and hydrated copolymer has ravnovesie is sustained fashion is hard at normal room temperature, and in the hydrated state is flexible at normal room temperature.

In the hydrated state, the copolymer preferably has a refractive index higher than 1.50.

In an UN-hydrated state, the copolymer may be subjected to mechanical processing at normal room temperature.

This copolymer can be used in ophthalmic device. This ophthalmological device preferably is an intraocular lens.

The copolymer may optionally contain a crosslinking agent.

The copolymer preferably has a glass transition temperature above room temperature, may be subjected to mechanical processing at normal room temperature and has a refractive index higher than 1.50.

The first Monomeric component is preferably corresponds to the formula:

where Z is-H or-CH3,

Q is Deputy containing at least one aromatic ring.

Q can be selected from the group comprising: phenyl ether ethylene glycol phenyl ether of polyethylene glycol, phenyl, 2-ethylenoxy, existence, benzyl, 2-phenylethyl, 4-were, 4-IU who yl)phenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 2-(4-cyclohexylphenol)ethyl, 2-(2-chlorophenyl)ethyl, 2-(3-chlorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(4-bromophenyl)ethyl, 2-(3-phenylphenyl)ethyl, 2-(4-phenylphenyl)ethyl, 2-(4-benzoylphenyl)ethyl.

The first Monomeric component can be selected from the group consisting of an ester of acrylic acid and phenyl ether of ethylene glycol, ester of acrylic acid and phenyl ether of polyethylene glycol, fenilsalicilat, 2-ethylenemethacrylic, 2-ethylenemethacrylic, paxilparoxetinerf, existentialist, bezelmaterial, 2-fenilatilmalonamid, 4-methylphenylethyl, 4-methylbenzonitrile, 2-2-methylphenylacetonitrile, 2-3-methylphenylacetonitrile, 2-4-methylphenylacetonitrile, 2-(4-propylphenyl)ethyl methacrylate, 2-(4-(1-methylethyl)phenyl)ethyl methacrylate, 2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenol)ethyl methacrylate, 2-(2-chlorophenyl)ethyl methacrylate, 2-(3-chlorophenyl)-ethyl methacrylate, 2-(4-chlorophenyl)ethyl methacrylate, 2-(4-bromophenyl)ethyl methacrylate, 2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethyl methacrylate), 2-(4-benzoylphenyl)-ethyl methacrylate, and mixtures thereof.

The first Monomeric component is preferably selected from the group consisting of a complex ester of acrylic acid and phenyl ether etilenglikole contains, at least 10 weight percent of the first Monomeric component.

The second Monomeric component preferably contains a substituted styrene or unsubstituted styrene.

The second Monomeric component can be selected from the group consisting of styrene and styrene substituted by at least one halogen, lower alkyl or lower alkoxysubstituted.

The second Monomeric component is preferably selected from the group consisting of styrene and chloresterol.

The copolymer preferably contains at least 10 weight percent of the second monomer component.

The third Monomeric component may contain methacrylate without aromatic substituent.

The third Monomeric component can be selected from the group consisting of hydroxyethylmethacrylate, hydroxyethoxymethyl, hydroxyethoxymethyl, ethoxyethylacetate, methoxyethoxymethyl, methoxydibenzoylmethane, etilenglikolevykh, n-vinyl-2-pyrrolidone, methacrylic acid, vinyl acetate and mixtures thereof.

The third Monomeric component is preferably selected from the group consisting of hydroxyethylmethacrylate, hydroxyethoxymethyl is in the third Monomeric component.

A crosslinking agent is preferably diacrylate or dimethacrylate.

The task was also solved another way of carrying out the invention, and it is capable of hydration of the copolymer.

Capable of hydration of the copolymer according to the invention contains:

a) at least 20 weight percent of the first Monomeric component selected from the group consisting of a complex ester of acrylic acid and phenyl ether of ethylene glycol, and complex ester of acrylic acid and phenyl ether of polyethylene glycol;

b) at least 10 weight percent of the second Monomeric component selected from the group consisting of substituted of unsubstituted styrene and styrene;

C) at least 10 weight percent of the third Monomeric component selected from the group consisting of hydroxyethylmethacrylate, hydroxyethoxymethyl and methacrylic acid; and

g) less than 10 weight percent of a crosslinking agent selected from the group consisting of diacrylate and etilenglikolevykh, and the copolymer has a refractive index higher than about 1.50 and after hydration is flexible at normal room temperature.

A crosslinking agent predpochtitelno contains an ester of acrylic acid and phenyl ether of ethylene glycol, the second Monomeric component includes styrene, the third Monomeric component includes hydroxyethylmethacrylate and a crosslinking agent contains etilenglikolevykh.

The copolymer preferably contains:

a) less than 50 weight percent of the first monomer component;

b) less than 40 weight percent of the second monomer component;

C) at least 60 weight percent of a third monomer component; and

g) at least 1 weight percent of a crosslinking agent.

This copolymer preferably contains:

from 30 to 45 weight percent of ester of acrylic acid and phenyl ether of ethylene glycol, of ester of acrylic acid and phenyl ether of polyethylene glycol or mixtures thereof; from 20 to 30 weight percent styrene; from 25 to 40 weight percent of hydroxyethylmethacrylate, hydroxyethylmethacrylate or mixtures thereof and from 1 to 5 weight percent cross-linking agent.

The task was solved by the following invention of the ophthalmic device.

Ophthalmologic device according to the invention contains capable of hydration of the copolymer, and the copolymer contains:

a) at least 20 weight preteenlola ether of ethylene glycol, and complex ester of acrylic acid and phenyl ether of polyethylene glycol;

b) at least 10 weight percent of the second Monomeric component selected from the group consisting of substituted of unsubstituted styrene and styrene;

C) at least 10 weight percent of the third Monomeric component selected from the group consisting of hydroxyethylmethacrylate, hydroxyethoxymethyl and methacrylic acid; and

g) less than 10 weight percent of a crosslinking agent selected from the group consisting of diacrylate and etilenglikolevykh, and the copolymer has a refractive index higher than 1.50 and after hydration is flexible at normal room temperature.

Ophthalmic device may be an intraocular lens.

The task was solved by another invention is a method of manufacturing an intraocular lens. A method of manufacturing an intraocular lens according to the invention comprises the stage of:

a) getting hard, capable of hydration of the copolymer containing the first Monomeric component comprising arylaryl or allmaterial; the second Monomeric component, which contains a monomer having an aromatic ring with substituent having at least one unsaturated adilgeray monomer, are capable of forming hydrogels with high water content, and the copolymer has a glass transition temperature above normal room temperature;

b) receiving from the hard copolymer solid intraocular lens having the required dimensions; and

C) hydration of the copolymer with obtaining flexible hydrated intraocular lens, and hydrated intraocular lens has an equilibrium water content of less than 10 weight percent and a refractive index higher than 1.55.

The volume of hard intraocular lenses hydrated and soft intraocular lens preferably differ by less than 10%.

This intraocular lens preferably is a lens power of 20 diopters and has a thickness in the centre of less than 0.4 millimeters.

In this method, the copolymer preferably hydratious:

placing the copolymer in an aqueous solution;

gradually increasing the temperature of the aqueous solution up to 40C;

maintaining the aqueous solution at 40C for at least 10 minutes;

gradually increasing the temperature of the aqueous solution to 60C;

maintaining the aqueous solution at 60C for at least one hour and gradually lowering Stateline is produced by cutting a lens from a solid sheet of a copolymer and polishing lenses.

The task was solved by another invention is a method of ophthalmic implant device in the eye.

The method of the ophthalmic implant device into the eye according to the invention contains stages: obtaining capable of hydration ophthalmic device made of a copolymer under item 1, which at room temperature is hard when dry, and flexible in a hydrated state; hydration capable of hydration of the ophthalmic device; cooking syringe containing hydrated ophthalmic device; and the introduction of the ophthalmic device in the eye.

This ophthalmological device preferably is an intraocular lens.

While capable of hydration ophthalmic device preferably contains a copolymer including:

a) a first Monomeric component containing arylaryl or allmaterial;

b) a second Monomeric component containing a monomer having an aromatic ring with substituent containing at least one unsaturated ethylene fragment, and the second Monomeric component is an acrylate; and

C) format.

Ophthalmological device is introduced into the eye through an incision, the length of which is preferably less than 1 millimeter.

The task was also decided copolymer.

The copolymer according to the invention was obtained by the method containing the steps:

a) mixing a first monomer component, a second Monomeric component, the third Monomeric component and a crosslinking agent to obtain a reaction mixture,

the first Monomeric component includes arylaryl or allmaterial; the second Monomeric component includes a monomer having an aromatic ring with substituent having at least one unsubstituted ethylene fragment, and the second Monomeric component is an acrylate; and a third Monomeric component includes a monomer capable of forming hydrogels with high water content;

b) maintaining the reaction mixture under the conditions necessary for carrying out the polymerization to obtain a copolymer.

An essential novelty of the polymer material according to this invention consists in the fact that he (a) is rigid enough that it can be machined at room temperature, and (b) can the and can be gidratirovana to achieve the desired degree of softness when it absorbs minimal amounts of water. The absorption of a relatively small amount of water allows for effective hydration, without affecting the mechanical or optical properties without changing the size or the refractive index of soft lenses. Another important advantage of the invention is the ability to turn the lens during polishing to obtain a smooth and rounded edges. Partly this contributes to the relatively high glass transition temperature (Tarticlematerial.

On the one hand, the invention is a composition capable of representing the hydration of the copolymer. The copolymer contains:

a) a first Monomeric component, which ailability or allocability;

b) a second Monomeric component containing a monomer having an aromatic ring with the Deputy has at least one unsaturated ethylene fragment, and the second Monomeric component is an acrylate; and

C) a third Monomeric component containing a monomer capable of forming a hydrogel with high water content. Preferably the copolymer further comprises a crosslinking agent.

On the other hand, this invention is ophthalmologically a method of manufacturing ophthalmic devices, such as intraocular lenses, of the polymer(s) according to this invention. The method typically includes the formation of a rigid polymer billet of a copolymer according to this invention, the execution of the ophthalmic devices of the workpiece and hydration ophthalmic device to the desired soft and flexible condition so that if desired it can be bent.

This invention is also a method of ophthalmic implant device in the eye. The method includes obtaining capable of hydration ophthalmic devices, which at room temperature is hard in the dry state and flexible after hydration. Ophthalmological device hydratious and prepare the syringe containing hydrated ophthalmic device. After that, the ophthalmic device is introduced into the eye.

INFORMATION CONFIRMING the POSSIBILITY of carrying out the INVENTION

The polymer material according to this invention contains a polymer units resulting from the polymerization of the first, second and third Monomeric components. These components may contain aryl(meth)acrylate, an aromatic monomer and a monomer, the method of the second agent. In more detail each of the components described below.

The composition may also contain (but optional) other monomer components, the initiator or material that absorbs in the ultraviolet (UV) region of the spectrum. The proportion of monomers should preferably be selected in such a way as to provide enough of a hard polymer having a glass transition temperature of at least about normal room temperature. Each of the three different Monomeric components are preferably present in the copolymer in amounts of at least 10 weight percent, more preferably in the amount of at least 20 weight percent. This invention provides for statistical and block copolymers of stated here Monomeric components. Except where otherwise indicated, all weight percentages calculated from the total weight of the composition before polymerization.

In a particularly preferred embodiment, the composition is a capable of hydration of the copolymer, which includes:

a) at least 20 weight percent of the first monomer component, such as an ester of acrylic acid is I;

b) at least 10 weight percent of the second monomer component, such as styrene or substituted styrene;

C) at least 10 weight percent of a third monomer component, such as hydroxyethylmethacrylate, hydroxyethoxymethyl or methacrylic acid; and

g) less than 10 weight percent cross-linking agent, such as diacrylate or dimethacrylate. The resulting copolymer has a refractive index higher than about 1.50 and after hydration is flexible at normal room temperature (i.e. about 20-25C).

The MONOMERS

Typically, the first Monomeric component is ailability or allocability. These compounds can also be named aryl(meth)acrylate monomers. The term "aryl" means that the compound contains at least one aromatic group. Such compounds generally correspond to the formula (I):

where Z is-H or-CH3and Q contains at least one aromatic ring.

Typical substituents Q include, but are not limited to: phenyl ether of ethylene glycol, polyacrylate phenyl ether ethylene glycol phenyl, 2-ethylenoxy, existence, benzyl, 2-fenile the Nile)ethyl, 2-4-(1-methylethyl)phenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 2-(4-cyclohexylphenol)ethyl, 2-(2-chlorophenyl)ethyl, 2-(3-chlorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(4-bromophenyl)ethyl, 2-(3-phenylphenyl)ethyl, 2-(4-phenylphenyl)ethyl, 2-(4-benzoylphenyl)ethyl and similar.

Suitable aryl(meth)acrylic monomers include, for example: esters of acrylic acid and phenyl ether of ethylene glycol (ALLEA), ester of acrylic acid and phenyl ether of polyethylene glycol (politea), fenilsalicilat, 2-ethylenemethacrylic, 2-ethylenemethacrylic, paxilparoxetinerf, existentialist, bezelmaterial, 2-fenilatilmalonamid, 4-methylphenylethyl, 4-methylbenzonitrile, 2-2-methylphenylacetonitrile, 2-3-methylphenylacetonitrile, 2-4-methylphenylacetonitrile, 2-(4-propylphenyl)ethyl methacrylate, 2-(4-(1-methylethyl)phenyl)ethyl methacrylate, 2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenol)ethyl methacrylate, 2-(2-chlorophenyl)ethyl methacrylate, 2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chlorophenyl)ethyl methacrylate, 2-(4-bromophenyl)ethyl methacrylate, 2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethyl methacrylate, 2-(4-benzoylphenyl)ethyl methacrylate, and similar, including the corresponding methacrylates and acrylates, and mixtures thereof. It is likely that in this izobreteniya ALLEA, polilla.

The first Monomeric component should be added to the composition in an amount sufficient to provide a high refractive index, moderate water absorption and increased rigidity of the main chain. Preferably the first monomer component is at least about 10 weight percent of the composition; more preferably, at least about 20 weight percent; most preferably, at least about 30 weight percent. The first Monomeric component should be added in such quantity, in order to avoid undesirable low glass transition temperature of the resulting copolymer. Preferably the first monomer component is contained in the composition at less than about 60 weight percent; more preferably less than about 50 weight percent; most preferably less than about 45 weight percent.

The second Monomeric component includes a monomer having an aromatic ring with a substituent and has at least one unsaturated ethylene fragment. Preferably this second Monomeric component is an acrylate. These monomers correspond to the General formula (II):

where X is-H or-CH3and Ah I will win, for example, substituted and unsubstituted compounds styrene. These compounds may have such substituents as hydrogen, halogen (such as Br, Cl, F), lower alkyl groups (e.g. methyl, ethyl, propyl, butyl, isopropyl) and/or low alkoxygroup. You should not use monomers containing acrylic or acrylamide fragments. Suitable aromatic monomers include, for example: styrene, mitoxantron and chloresterol. Styrene and chloresterol are preferred. Most preferred is styrene.

The second Monomeric component should be added in sufficient quantity to increase the glass transition temperature of the resulting copolymer to the desired operating temperature. It is believed that the second Monomeric component provides a higher refractive index due to the aromatic ring, hydrophobicity and higher glass transition temperature. Preferably, the second monomer component is at least about 10 weight percent of the composition; more preferably at least about 15 weight percent; most preferably at least about 20 weight percent. The second Monomeric component should be added in such cragie desirable properties of the copolymer. Preferably, the second monomer component is less than about 60 weight percent of the composition; more preferably less than about 40 weight percent; most preferably less than about 30 weight percent.

The third Monomeric component includes a monomer capable of forming a hydrogel with high water content. Preferably, the third monomer component contains methacrylate without aromatic substituent. The list of suitable monomers capable of forming a hydrogel with high water content, and includes, for example: hydroxyethylmethacrylate (HEMA), hydroxyethoxymethyl (GEEMA), hydroxyethoxymethyl, methoxyethylmercury, methoxyethoxymethyl, methoxydibenzoylmethane, etilenglikolevykh, n-vinyl-2-pyrrolidone, methacrylic acid, vinyl acetate and similar, and mixtures thereof. For specialists in this field of technology is evident that there are a lot of other monomers capable of forming hydrogels with high water content, which seem to be quite suitable for use according to this invention. The preferred monomers are GAME and GEEMA.

The third Monomeric component W is for hydration. Preferably, the third monomer component is at least about 10 weight percent of the composition; more preferably, at least about 20 weight percent; most preferably, at least about 25 weight percent. The third Monomeric component should be added in sufficiently small quantities to avoid a statistically significant extension of the copolymer of hydration. Preferably, the third monomer component is less than about 60 weight percent of the composition; more preferably less than about 50 weight percent; most preferably less than about 40 weight percent.

The copolymer may also contain a crosslinking agent. Capable of copolymerization, cross-linking agent(s) applicable to obtain a copolymer materials according to this invention, includes any compound having an unsaturated ethylene fragment at one end and containing more than one unsaturated group. Preferred cross-linking agent are diacrylate or dimethacrylate. A crosslinking agent may also contain compounds having at least two (meth)acrylate and/or vinyl groups. Especially preferred crosslinking agents include on the performance are hydrogen atom or methyl group and a represents a substituted or unsubstituted divalent hydrocarbonyl group. In a preferred embodiment of formula (III), A represents a substituted or unsubstituted divalent aliphatic radical and preferably alkene containing 1-6 carbon atoms.

Typical crosslinking agents include, for example: diacrylate connections, including etilenglikolevykh (EGDM), detranscendentalized, polietilenglikolmonostearat, alkylbetaine, 1-3-propeciageneric-alismataceae, 1,6-hexaniacinate, 1,3-potentialtheorie, 1,4-butanediol-dimethacrylate, as well as connections deviceloop series, including divinelvie hydrocarbons and divinylbenzene and similar. Preferred cross-linking agent is etilenglikolevykh.

Crosslinking agent should be added in a quantity sufficient to bent hydrated copolymer could return to the original shape. Preferably a crosslinking agent contained in the composition in amounts of at least about 1 weight percent; more preferably, at least about 3 weight percent. At the same time, the number of added cross-linking agent should be small enough to avoid getting too hard or brittle copolymer. Predpochtitelnei 5 weight percent.

For specialists in the art it is obvious that depending on the intended use of the material to the polymer according to this invention can be optionally (but not necessarily) added additional components, such as agents that block the ultraviolet (UV), coloring agents and other Typical UV pagewise materials include, for example, those described in column 5, line 3-29 U.S. patent No. 5433746 name Namdaran and other Acceptable UV-absorbing agents include, for example, benzophenone, vinylbenzene and benzotriazol. In that case, if you use a UV-absorbing material, it is preferably added at a concentration of less than about 1% relative to the total weight of the composition.

The copolymers of this invention can be obtained using traditional methods of polymerization. For example, the monomers can be mixed together and heated to elevated temperature to facilitate the polymerization reaction. In order to facilitate the reaction and/or increase the speed of the polymerization reaction, the monomer mixture can be introduced catalysts and/or initiators, for example, selected from materials well known in the prior art. Typical initiators of n acetyl, peroxide Laurila, peroxide tert-butyl and similar, and mixtures thereof. It is preferable 2-2’-azobisisobutyronitrile (AIBN).

WAY

We now turn to the method of manufacturing ophthalmic devices of the copolymer. The method includes the following basic stages. From a mixture of first, second and third Monomeric components disclosed in this description, get a solid, capable of hydration of the copolymer. The copolymer has a glass transition temperature above about room temperature and refractive index higher than about 1.55. The rigid copolymer is then formed in the rigid ophthalmic device having the required dimensions. After that, the copolymer is subjected to hydration to obtain a flexible hydrated ophthalmic device. Preferably the hydrated copolymer has an equilibrium water concentration less than about 10 weight percent and a refractive index above about 1.55.

More specifically, the copolymer of this invention is generally formed into the shape of a thin sheet or rod. Solid ophthalmic device is usually made by cutting the workpiece, such as a rigid sheet of a copolymer, and polishing device. Ophthalmological us the ways of cutting on a lathe at room temperature. The device can be polished using traditional methods of polishing, such as surface finishing process. Ophthalmological device preferably is an intraocular lens (IOL).

The resulting ophthalmic device then hydratious. The hydration is carried out by soaking ophthalmic device in an aqueous solution (such as water or salt solution), preferably at elevated temperature (for example, at temperatures from 20-100C) for a time sufficient to saturate the device with water (for example, during the time from several minutes to several hours or longer).

Ophthalmic or other device, is made of a polymer according to this invention, substantially no increase in volume and does not change the shape of hydration. In other words, there is no statistically significant difference between the diameter and the thickness of the dry and hydrated products. Thus, in the case of IOL hard intraocular lens hydrated and soft intraocular lens have almost the same sizes.

PROPERTIES of the COPOLYMER

The copolymers according to this invention possess a unique combination which you high glass transition temperature, optical purity, ability to hydration and flexibility (softness) in the hydrated state.

Particularly advantageous combination of properties of the copolymers, flexible at room temperature, despite the fact that their glass transition temperature is above room temperature, and which also have a refractive index (KP) higher than about 1.50. Due to the fact that the refractive index of hydrated copolymer above 1.50 (and preferred copolymers have a refractive index above about 1.55), these copolymers are particularly attractive for use in ophthalmic devices such as intraocular lenses. The optical power of the lens depends on their shape and refractive index of the material from which they are made. Lenses made of a material with a higher refractive index, can be thinner with the same optical power as the lens is made of a material with a relatively lower refractive index. Thinner lenses are easier to enter, they cause less trauma during surgery. Thus, as a rule, ceteris paribus, the higher the coefficient SS="ptx2">The mechanical properties of the copolymer, such as the glass transition temperature, allow it to cut and Polish (i.e. machining) at room temperature (and not be molded or processed at low temperatures). The dry copolymer is rigid at normal room temperature and hydrated at the same temperature is flexible. In other words, the dry copolymer is sufficiently rigid or solid at room temperature, so it can be cut by traditional methods or process on a lathe; at the same time, hydrated copolymer is sufficiently flexible at normal room temperature, so that it can be bent 180 degrees without cracking. Useful as is also the fact that the dry copolymer is not too fragile.

The ability to cut and Polish ophthalmological device facilitates the fabrication of lenses with minimal, which only allows the refractive index of the material, the thickness in the center. Thus, of the copolymer of this invention can be made thinner lenses than from material having the same refractive index, but want to mould in otdelno 0.4 millimeters (mm). The small thickness of the lens, in turn, allows you to enter a copolymer through an incision of about 1 mm or less. This provides a significant advantage in the field of ophthalmic surgery, which is common to much larger incisions.

As for the glass transition temperature (Tarticle) copolymer, it preferably greater than normal room temperature, so that the copolymer can be processed by traditional methods and cutting on a lathe. Preferably Tarticlemore than 20 s, more preferably greater than 25 ° C, and most preferably greater than 30C. Can also be made relevant ophthalmic devices made from copolymers having a glass transition temperature above normal body temperature. Tarticledetermine by the method of differential scanning calorimetry (DSC).

As discussed above, the copolymer according to this invention becomes flexible when hydration. The hydration process opens up the possibility of highly efficient distribution of water molecules across the structure of the IOL, which causes the transformation of the hard polymer in the soft and flexible when it absorbs minimal amounts of water. The hydrated copolymer has a weight, more preferably less than about 5% and most preferably less than about 4% by weight. This slight absorption of water provides an effective hydration without adverse effects on the mechanical or optical properties of a flexible (soft) lenses. For example, neither the size of the lenses or refractive index did not significantly change during hydration. With regard to the extension of hydration, the copolymer according to this invention tend to expand less than about 10 volume percent, compared with an UN-hydrated copolymer; preferably, the volume percent expansion during hydration is less than about 5%. The percentage of expansion calculated by measuring the difference between the standard sizes of tablets before and after hydration.

Thus, the copolymer of this invention has a desirable and unique combination of properties, including the ability to machining in an UN-hydrated condition and minimal expansion during hydration; the copolymer also has a relatively high refractive index.

The METHOD of performing the SURGICAL INTERVENTION

Using the copolymer according to this invention, it is possible to assessmente local anesthesia to the eye in the eye, you can enter IOL, made of a new copolymer material. This method does not require the use of threads.

The method of implantation ophthalmic device in the eye can be made by manufacturing capable hydration ophthalmic devices, which at room temperature in a dry form is hard, and in the hydrated state at room temperature is flexible. Ophthalmological device hydratious and prepare the syringe containing hydrated ophthalmic device. Then ophthalmological device, which preferably is an intraocular lens made of a copolymer according to this invention, is injected into the eye. Perhaps the introduction of the ophthalmic device into the eye through the incision, the length of which is less than about 1.5 millimeters.

The lens can be entered using the device, for example such as described in U.S. patent No. 4715373 name Mazzocco. Form or the anchoring system used for the location of the IOL in the eye, it does not matter for the present invention. The copolymers can be used in soft intraocular lens having multiple anchoring systems. See, for example, U.S. patent No. 5776191 on them is these copolymers were obtained by mixing the following ingredients under reduced pressure: first, the second and third Monomeric component, a binder and polymerized with UV-blocking agent. As a UV blocking agent used vinylbenzoate at a total concentration of 0.3% by weight. To initiate polymerization used free-radical initiator 2-2’-azobisisobutyronitrile (AIBN) at a concentration of 0.2% by weight. The solution of monomers was stirred glass vessel with a magnetic stirrer for 30 minutes. After that, the solution was filtered through a filter of 0.2 μm () and injectively in shape, having a form of thin sheet consisting of two glass plates held together by means of spring holders and separated by a plastic spacer. The form is then placed in a water bath for 10 hours at 60C, then was taken out and kept for additional hardening at C in thermostat for 12 hours. Got a solid transparent polymer sheet.

Intraocular lenses with different diopters (5, 10, 20, and 34) cut from a solid polymeric sheet using traditional methods of machining, such used for the production of IOL polymethyl methacrylate (PMMA).

Joly polished in the drum (subjected to surface finishing process) for 2 days at 20C. Polio is this Joly was placed in a separate container, filled with salt solution. The vessel was placed in a thermostat with adjustable temperature and subjected to processing according to the following scheme: increased temperature from 20 to 40 ° C with a speed of 10 degrees per hour. Kept at 40C for 30 minutes. Was the temperature from 40 to 60C with a speed of 10 degrees per hour. Kept at 60C for 4 hours. Reduced the temperature from 60C to room temperature (about 20C) with a speed of 10 degrees per hour. After that Joly become soft and easy to bend and have excellent optical properties. The size of the lens (optical size, thickness, diameter) did not significantly change during hydration. It is established that the surface and edges of the samples are very smooth.

Using gravimetric analysis determined the equilibrium content of water after hydration. Also measured the refractive index and glass transition temperature of the lens. The results are shown in table 1.

In the following table 2, the term "opportunity machining" refers to the cutting of UN-hydrated material on a lathe, in which the diamond cutter during rotation at high speed comes into contact with the material. The term "good opportunity masegosa device can be selected in advance. The term "valid possibility of mechanical processing" means that the material may be subjected to mechanical processing, if the environmental parameters can be controlled, for example, by lowering the temperature. The term "bad possibility of mechanical processing" means that the material has a tendency to deformation or destruction in the process of cutting on a lathe, but it can still be subjected to mechanical processing, if the environmental parameters are monitored. The term "not subject to mechanical processing" means that the material cannot be cut on a lathe and should be molded in other ways, such as forming in a separate form. The term "flexibility" refers to the ability to bend the material to the value of up to 180 without destruction, provided that the material was gidratirovana. The term "good flexibility" means that the material is cut into disks of a size approximately corresponding to the size of a standard lens, you can bend it with tweezers. The term "permissible flexibility" means that the hydrated disc of material bent upon certain effort. The term "poor flexibility" means that the hydrated disc bends without failure is ratatsii, studies have been conducted hydration. Used on twenty samples made in accordance with the formulation of each composition shown in table 1. The samples were disks with a diameter of 16.5 mm and a thickness of 2.0 mm For each composition the results were averaged (see table 3).

After hydration, the size was not changed.

1. Capable of hydration of the copolymer containing (a) a first Monomeric component containing arylaryl or allmaterial; b) a second Monomeric component containing a monomer having an aromatic ring with substituent with at least one unsaturated ethylene fragment, and the second Monomeric component is an acrylate; and C) a third Monomeric component containing a monomer capable of forming hydrogels with high water content.

2. The copolymer under item 1, characterized in that when hydration is flexible, and when the hydration of the size of the copolymer increases by less than 10% vol. compared to the UN-hydrated copolymer.

3. The copolymer under item 1, characterized in that during the hydration it becomes flexible and hydrated copolymer has an equilibrium water content of less than 5 wt.%.

5. The copolymer under item 2, characterized in that in the hydrated state has a refractive index higher than 1,50.

6. The copolymer under item 2, characterized in that the UN-hydrated state can be subjected to mechanical processing at normal room temperature.

7. The copolymer under item 1, characterized in that it is designed for use in ophthalmic device.

8. The copolymer under item 7, wherein the ophthalmic device is an intraocular lens.

9. The copolymer under item 1, characterized in that it further contains a crosslinking agent.

10. The copolymer under item 1, characterized in that it has a glass transition temperature above room temperature.

11. The copolymer under item 1, characterized in that may be subjected to mechanical processing at normal room temperature and has a refractive index higher than 1,50.

12. The copolymer under item 1, wherein the first Monomeric component corresponds to the formula

where Z is-H or-CH3;

Q is Deputy containing at least one aromatic Koirala, phenyl ether of polyethylene glycol, phenyl, 2-ethylenoxy, existence, benzyl, 2-phenylethyl, 4-were, 4-methylbenzyl, 2-2-methylphenylethyl, 2-3-methylphenylacetonitrile, 2-4-methylphenylethyl, 2-(4-propylphenyl)ethyl, 2-4-(1-methylethyl)phenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 2-(4-cyclohexylphenol)ethyl, 2-(2-chlorophenyl)ethyl, 2-(3-chlorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(4-bromophenyl)ethyl, 2-(3-phenylphenyl)ethyl, 2-(4-phenylphenyl)ethyl, 2-(4-benzoylphenyl)ethyl.

14. The copolymer under item 1, wherein the first Monomeric component is selected from the group consisting of an ester of acrylic acid and phenyl ether of ethylene glycol, ester of acrylic acid and phenyl ether of polyethylene glycol, fenilsalicilat, 2-ethylenemethacrylic, 2-ethylenemethacrylic, paxilparoxetinerf, existentialist, bezelmaterial, 2-fenilatilmalonamid, 4-methylphenylethyl, 4-methylbenzonitrile, 2-2-methylphenylacetonitrile, 2-3-methylphenylacetonitrile, 2-4-methylphenylacetonitrile, 2-(4-propylphenyl)ethyl methacrylate, 2-(4-(1-methylethyl)phenyl)ethyl methacrylate, 2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenol)ethyl methacrylate, 2-(2-chlorophenyl)ethyl methacrylate, 2-(3-chlorophenyl)-ethyl methacrylate, 2-(4-chlorophenyl)ethyl methacrylate, 2-(4-bromophenyl)edelmetall

15. The copolymer under item 1, wherein the first Monomeric component is selected from the group consisting of a complex ester of acrylic acid and phenyl ether of ethylene glycol, and complex ester of acrylic acid and phenyl ether of polyethylene glycol.

16. The copolymer under item 1, characterized in that it contains at least 10 wt.% the first Monomeric component.

17. The copolymer under item 1, wherein the second Monomeric component contains a substituted styrene or unsubstituted styrene.

18. The copolymer under item 1, wherein the second Monomeric component is selected from the group consisting of styrene and styrene substituted by at least one halogen, lower alkyl or lower alkoxy-Deputy.

19. The copolymer under item 1, wherein the second Monomeric component is selected from the group consisting of styrene and chloresterol.

20. The copolymer under item 1, characterized in that it contains at least 10 wt.% the second Monomeric component.

21. The copolymer under item 1, wherein the third Monomeric component contains methacrylate without aromatic substituent.

22. The copolymer under item 1, wherein the third Monomeric component is selected from the group consisting of gerlat, methoxyethoxymethyl, methoxydibenzoylmethane, etilenglikolevykh, n-vinyl-2-pyrrolidone, methacrylic acid, vinyl acetate and mixtures thereof.

23. The copolymer under item 1, wherein the third Monomeric component selected from the group consisting of hydroxyethylmethacrylate, hydroxyethoxymethyl and methacrylic acid.

24. The copolymer under item 1, characterized in that it contains at least 10 wt.% the third Monomeric component.

25. The copolymer under item 9, characterized in that the crosslinking agent is diacrylate or dimethacrylate.

26. Capable of hydration of the copolymer containing (a) at least 20 wt.% the first Monomeric component selected from the group consisting of a complex ester of acrylic acid and phenyl ether of ethylene glycol, and complex ester of acrylic acid and phenyl ether of polyethylene glycol; b) at least 10 wt.% the second Monomeric component selected from the group consisting of substituted of unsubstituted styrene and styrene; b) at least 10 wt.% the third Monomeric component selected from the group consisting of hydroxyethylmethacrylate, hydroxyethoxymethyl and methacrylic acid; and d) less than 10 wt.% car has a refractive index higher than about 1.50 and after hydration is flexible at normal room temperature.

27. The copolymer under item 26, characterized in that the crosslinking agent is etilenglikolevykh.

28. The copolymer under item 26, characterized in that the first monomer component contains an ester of acrylic acid and phenyl ether of ethylene glycol, the second Monomeric component includes styrene, the third Monomeric component includes hydroxyethylmethacrylate and a crosslinking agent contains etilenglikolevykh.

29. The copolymer under item 26, characterized in that it contains a) less than 50 wt.% the first Monomeric component; b) less than 40 wt.% the second Monomeric component; C) at least 60 wt.% the third Monomeric component and g) at least 1 wt.% cross-linking agent.

30. The copolymer under item 26, characterized in that it contains from 30 to 45 wt.% of ester of acrylic acid and phenyl ether of ethylene glycol, of ester of acrylic acid and phenyl ether of polyethylene glycol or mixtures thereof; b) from 20 to 30 wt.% styrene; b) from 25 to 40 wt.% hydroxyethylmethacrylate, hydroxyethylmethacrylate or mixtures thereof and d) from 1 to 5 wt.% cross-linking agent.

31. Ophthalmological device, capable of containing the hydration of the copolymer, and the copolymer contains (a) at least 20 wt.% the first monomer to the Olya and complex ester of acrylic acid and phenyl ether of polyethylene glycol; b) at least 10 wt.% the second Monomeric component selected from the group consisting of substituted of unsubstituted styrene and styrene; b) at least 10 wt.% the third Monomeric component selected from the group consisting of hydroxyethylmethacrylate, hydroxyethoxymethyl and methacrylic acid; and d) less than 10 wt.% cross-linking agent selected from the group consisting of diacrylate and etilenglikolevykh, and the copolymer has a refractive index higher than 1.50 and after hydration is flexible at normal room temperature.

32. Ophthalmological device according to p. 31, characterized in that it is an intraocular lens.

33. A method of manufacturing an intraocular lens, comprising stages a) obtaining a hard capable of hydration of the copolymer containing the first Monomeric component comprising arylaryl or allmaterial; the second Monomeric component, which contains a monomer having an aromatic ring with substituent having at least one unsaturated ethylene fragment, and the second Monomeric component is an acrylate; and the third monomer component containing a monomer capable of forming hydrogelator; b) receiving from the hard copolymer solid intraocular lens having the required dimensions; and b) hydration of the copolymer with obtaining flexible hydrated intraocular lens, and hydrated intraocular lens has an equilibrium water content of less than 10 wt.% and the refractive index above 1.55.

34. The method according to p. 33, characterized in that the volume of hard intraocular lenses hydrated and soft intraocular lens differ by less than 10%.

35. The method according to p. 33, wherein the intraocular lens is a lens power of 20 diopters and has a thickness at the center is less than 0.4 mm

36. The method according to p. 33, characterized in that the copolymer hydratious placing the copolymer in aqueous solution, gradually increasing the temperature of the aqueous solution up to 40C, maintaining the aqueous solution at 40C for at least 10 minutes, gradually increasing the temperature of the aqueous solution to 60C, maintaining the aqueous solution at 60C for at least 1 h and gradually lowering the temperature of the aqueous solution to room temperature.

37. The method according to p. 33, characterized in that the solid intraocular lens obtained by cutting a lens from a solid sheet of a copolymer and polishing lenses.

3 the purpose ophthalmic devices, made of copolymer under item 1, which at room temperature is hard when dry, and flexible in a hydrated state; hydration capable of hydration of the ophthalmic device; cooking syringe containing hydrated ophthalmic device and the introduction of the ophthalmic device in the eye.

39. The method according to p. 38, wherein the ophthalmic device is an intraocular lens.

40. The method according to p. 38, characterized in that it is capable of hydration ophthalmic device is a copolymer comprising (a) a first Monomeric component containing arylaryl or allmaterial; b) a second Monomeric component containing a monomer having an aromatic ring with substituent containing at least one unsaturated ethylene fragment, and the second Monomeric component is an acrylate; and C) a third Monomeric component containing a monomer capable of forming hydrogels with high water content.

41. The method according to p. 38, wherein the ophthalmic device is introduced into the eye through an incision, the length of which is less than 1 mm

42. The copolymer obtained by the method, the soda is th component and a crosslinking agent to obtain a reaction mixture, the first Monomeric component includes arylaryl or allmaterial; the second Monomeric component includes a monomer having an aromatic ring with substituent having at least one unsubstituted ethylene fragment, and the second Monomeric component is an acrylate; and a third Monomeric component includes a monomer capable of forming hydrogels with high water content; and b) maintaining the reaction mixture under the conditions necessary for carrying out the polymerization to obtain a copolymer.

Priority items:

12.04.1999 on PP.1-11, 14, 15, 25, 27, 32, 34-37 and 39;

22.07.1999 on PP.12, 13, 16-24, 26, 28-31, 33, 38, 40-42.

 

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