EA043007B1 - MATERIAL FOR MANUFACTURING OPHTHALMIC IMPLANTS BY PHOTOPOLYMERIZATION METHOD - Google Patents

Description

Technical field

The invention relates to the field of composite materials, specifically to materials used in medicine, in particular in ophthalmology for the manufacture of optical ophthalmic implants, mainly intraocular lenses (hereinafter referred to as IOLs), intended for vision correction after cataract removal.

In modern cataract surgery, one of the tasks is to create new IOLs that provide high visual functions to the patient and do not cause complications in the postoperative period. Most research is aimed at the development of hydrophobic IOLs, which, compared with hydrophilic lenses, have several advantages: they are more resistant to biodegradation, less likely to cause clouding of the posterior capsule in the postoperative period (secondary cataract), do not form vacuoles and glare, and are easier to implant due to the use of a pre-installation system . The pre-installation system for hydrophobic IOLs consists in the fact that the IOL is twisted with a special tool, which allows it to be implanted through a small incision. In the eye, the IOL independently straightens and takes the correct position.

As a rule, the IOL has a monolithic design and consists of an optical part and haptic elements. Haptic elements provide adaptation of the IOL to the size of the capsular bag and are pressed into the plane of the lens.

Prior Art

The material for the manufacture of implants is known from the prior art, disclosed in patent EP3323387B1 (publ. 02.10.2019, A61F2/16, C08G18/67, C08L75/16, C08G18/48, C08G18/76). Known material is a composition for the manufacture of ophthalmic implants by photopolymerization, which consists of:

a) 35-70 wt.% urethane di(meth)acrylate oligomer with terminal (meth)acrylate fragments, consisting of the following components:

(I) (meth)acrylate, (II) diisocyanate and (III) polyol and having the following structure:

hydroxy(meth)acrylate'-{(diisocyanate'-polyol-diisocyanate)}hydroxy(meth)acrylate, where one of the isocyanate groups of diisocyanate' and diisocyanate'', respectively, is connected to hydroxy(meth)acrylate' and hydroxy(meth) acrylate'' to form a urethane bond, and where the remaining isocyanate group of the diisocyanate' and diisocyanate'', respectively, is connected to the hydroxyl group of the polyol to form a urethane bond, where hydroxy(meth)acrylate' and hydroxy(meth)acrylate'' may be the same or different, and the diisocyanate' and diisocyanate'' may be the same or different. The polyol in the urethane di(meth)acrylate oligomer can be any branched chain aliphatic diol, as well as be a mixture of several;

b) 30-65 wt.% of a component from the group of (meth)acrylate monomers, such as: alkyl (meth)acrylates, aryl (meth)acrylates, alicyclic (meth)acrylates, fluorine-substituted (meth)acrylates, silicon-containing (meth)acrylates, any aromatic or aliphatic esters of unsaturated carboxylic acids of a non-(meth)acrylic series, as well as a mixture of these monomers, where the content of (meth)acrylate monomers with aromatic fragments is not less than 50 wt.% of the content of component b);

c) not less than 0.2% by weight of a UV absorbing component, such as a polymerizable UV filter comprising UV absorbing compounds of the benzophenone or benzotriazole series, or a combination thereof;

d) polymerization initiator.

At the same time, the specified material based on a biocompatible copolymer used for the production of hydrophobic ophthalmic implants is hydrophobic with an equilibrium water content at 37°C of less than 3.0 wt.%, and the content of (meth)acrylic acid in the composition of the specified biocompatible copolymer is less than 3 wt. .%.

The manufacture of ophthalmic implants according to a well-known patent is as follows. A finished product with a given shape and dimensions is obtained by curing a known material under the action of light between glass molds. This method guarantees optical purity, biocompatibility and biostability of the finished product. Known material makes it possible to obtain high-quality products only when using glass injection molds, on which a transparent pattern of the finished product is applied against the background of a material opaque to light (photomask). The specified method of production, for example, is described in patent RU22349391C2 Method for the manufacture of artificial eye lenses (publ. 20.08.2004, B29D11/00, A61F2/16). For the manufacture of artificial eye lenses according to this method, a mold is used, consisting of two halves made of an optically transparent material, such as quartz, and an annular spacer, the thickness of which is equal to the thickness of the supporting part of the lens. On the inner surface of the upper half of the mold, a pattern is made containing areas that are transparent and opaque to UV light, for example, from chromium, the negative image of which corresponds to a flat image of the optical

- 1 043007 parts of the lens and its supporting elements. A similar drawing is made on the inner surface of the second half of the mold, the negative image of which corresponds only to the optical part of the lens.

In this case, polymerization in opaque areas (dark) is almost excluded due to the lack of the possibility of light entering them. When carrying out the process of obtaining a finished product without using any patterns and coatings on glass injection molds, according to the principle of not contact, but already projection lithography, the disadvantage of the known material according to patent EP3323387B1 is the lack of control of the polymerization rate (inhibition for a significant time) in dark (non-illuminated) areas, the consequence of which is: the possible formation of defects at the end along the edge of the IOL - microprotrusions, which are perceived as an unfinished edge. It is also possible a significant change in the geometric dimensions (increase in width) of the haptic elements, which directly affects the physical and mechanical properties and as a result, the haptic elements will not compress correctly during implantation, and there may also be an incorrect position of the IOL in the capsular bag after implantation, if there are holes in the design of the IOL, these holes can swim and, as a result, do not fulfill their official purpose when installing the IOL.

The lack of control of the polymerization rate in the known material also makes it difficult to obtain a more uniform structure with less free volume and increases the likelihood of glistening.

Disclosure of invention

The technical result consists in providing control of the polymerization rate in order to eliminate defects in the profile of the ophthalmic implant, control geometric dimensions, reduce glistening of the finished product while maintaining optimal physical and mechanical properties.

The technical result is achieved due to the fact that the proposed material for the manufacture of ophthalmic implants by photopolymerization, containing:

a) 60-70 wt.% urethane di(meth)acrylate oligomer with terminal (meth)acrylate fragments, consisting of the following components:

(I) (meth)acrylate, (II) diisocyanate and (III) polyol and having the following structure:

hydroxy(meth)acrylate'-{(diisocyanate'-polyol-diisocyanate)}hydroxy(meth)acrylate, where one of the isocyanate groups of diisocyanate' and diisocyanate, respectively, is connected to hydroxy(meth)acrylate' and hydroxy(meth)acrylate' ' to form a urethane bond, and where the remaining isocyanate group of the diisocyanate' and diisocyanate, respectively, is connected to the hydroxyl group of the polyol to form a urethane bond, where hydroxy(meth)acrylate' and hydroxy(meth)acrylate'' may be the same or different and the diisocyanate 'and diisocyanate'' may be the same or different, wherein the polyol in the urethane di(meth)acrylate oligomer may be any branched chain aliphatic diol, as well as be a mixture of several;

b) 20-40% by weight of a component from the group of (meth)acrylate monomers with aromatic substituents in the side chain, comprising at least one of the following:

2-phenoxyethyl methacrylate, benzyl methacrylate, benzyl-2-ethyl acrylate, phenyl methacrylate;

c) 5-25% by weight of a component from the group of (meth)acrylate monomers with branched aliphatic substituents in the side chain, comprising at least one of the following: tert-butyl methacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate;

d) not less than 0.2 wt.% UV-absorbing component, such as a polymerizable UV filter, including UV-absorbing compounds of the benzophenone or benzotriazole series, or a combination thereof;

e) from 0.1 to 1 wt% of a photopolymerization initiator;

e) from 0.005 to 0.5 wt.% inhibitor of radical polymerization and includes at least one of the following:

4-tert-butylpyrocatechol, tert-butylhydroquinone,

1,4-benzoquinone,

6-tert-butyl-2,4-xylenol,

2-tert-butyl-1,4-benzoquinone,

3,5-di-tert-butyl-o-benzoquinone,

2,6-di-tert-butyl-p-cresol,

2,6-di-tert-butylphenol; hydroquinone,

- 2 043007

4-methoxyphenol.

The photopolymerization initiator, component e), is preferably selected from the following:

IRGACURE 369: 2-benzyl-2-(dimethylamino)-1-[4-(4-morpholinyl)phenyl]-1-butanone;

IRGACURE 651: 2,2-dimethoxy-2-phenylacetophenone;

DAROCUR TPO: 2,4,6-trimethylbenzoyl diphenyl phosphine oxide;

DAROCUR 4265: mixture of DAROCUR TPO and DAROCUR 1173: 2-hydroxy-2-methyl-1-phenyl-1-propanone;

IRGACURE 2100: a mixture of 2,4,6-trimethylbenzoyl-phenylphosphinic acid ethyl ester and IRGACURE 819: phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide;

IRGACURE 2022: mixture of IRGACURE 819 and DAROCUR 1173;

IRGACURE 2022: mixture of bis(2,6-dimethoxybenzoyl-2,4,4-trimethylpentyl)phosphine oxide and 2hydroxy-2-methyl-1-phenyl-propan-1-one.

As a UV blocking component, component d), the material may contain compounds of the diphenyl ketone type, such as 2-hydroxy-4-acryloyloxydiphenyl ketone, 2-(4-benzoyl-3-hydroxyphenoxy)-ethyl acrylate and polymerizable UV filters of the benzotriazole type, for example, 2-[3(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate, 2-[2-hydroxy-5-[2-(methacryloyloxy)ethyl]phenyl]-2H-benzotriazole. You can also use a combination of these components.

The material may additionally contain a component that absorbs the blue part of the spectrum.

The material for the manufacture of ophthalmic implants of the present invention is polymerized by light curing (photopolymerization method) in transparent injection molds without additional coatings. The method of obtaining the finished product by photopolymerization consists in irradiating the material with light that has previously passed through the appropriate photomask and has the appropriate wavelength, for example in the region from 340 nm to 450 nm, preferably from 360 nm to 430 nm, more specifically about 410 nm. The irradiation time can be from 1 minute to 7 minutes, preferably about 3 minutes. In particular, the photopolymerization method can be applied at 410 nm for 1-5 minutes, preferably for 3 minutes. The light source used in this case should preferably have a power of 1-5 mW/cm ² .

Embodiment of the invention

The invention can be illustrated by the following examples.

Example.

Test samples of the material for the manufacture of ophthalmic implants by photopolymerization with different compositions of the components presented in the table were prepared as follows. Samples of finished IOLs (+20 D) were obtained by curing between two corresponding glass molds using an LED light source with a wavelength of 405-410 nm and a power of 1-2 mW / cm ² , then the finished lenses, after washing from the remnants of the non-polymerized composition, additionally illuminated in a vacuum chamber using the same light source for 30 min. The cured samples were subjected to extraction with isopropyl alcohol at a temperature of 60-70°C for 5 hours, and then dried in vacuum for 12 hours at a temperature of 60°C.

Sample No. The composition of the composition Properties OUA, wt.% BenzMA, wt.% THEME, wt.% n-OMA, wt.% UV filter, wt.% Photoinitiator, wt.% DTBPK inhibitor, wt.% Polymerization rate, %/min Departure of dimensions into the dark region, exposure time 2 min Curing time without dimensional care, min X 62 25 - 10 2 0.25 - 64 There is 1.5 1 62 25 10 - 2 0.25 0.01 62 No 2.0 2 62 25 10 - 2 0.25 0.04 59 No 2.5 3 62 25 10 - 2 0.25 0.1 46 No 3.2

where the test sample X corresponds to the closest analogue for the proposed material for the manufacture of ophthalmic implants, disclosed in patent EP3323387B1, publ. 10/2/2019, A61F2/16, C08G18/67, C08L75/16, C08G18/48, C08G18/76.

Test samples 1-3 correspond to the proposed material for the manufacture of ophthalmic implants, but do not limit it.

OUA - urethane di(meth)acrylate oligomer with the structure:

- 3 043007 about

BenzMA - benzyl methacrylate, n-OMA - n-octyl methacrylate,

TBMA - tert-butyl methacrylate,

UV filter - 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate,

Photoinitiator - IRGTPO - 2,4,6-trimethylbenzoyldiphenylphosphine oxide,

DTBPK - 2,6-di-tert-butyl-p-cresol.

Brief description of the figures

The results of evaluating the kinetics of photopolymerization of the curable compositions according to the table of tested samples under irradiation with a LED light source with a wavelength of 405-410 nm and a power of 1-2 mW/cm ² are shown in the figure.

The figure shows that the addition of a radical polymerization inhibitor makes it possible to reduce the polymerization rate, especially at large amounts. In this case, the polymerization rates in the dark zone will decrease even more due to the low power of light entering this zone due to scattering and reflection. Thus, as follows from the figure and from the table, it is most preferable to use moderate amounts of inhibitor, on the order of 0.05 wt.%, since it is in this case that the greatest difference is observed between the time of complete curing (time t in the figure) in the irradiated area and the maximum exposure time, at which no results of polymerization in the dark zone are observed.

The test showed that in the test samples 1-3, the effect of glistening is much less pronounced than in sample X.

Claims (2)

Material for the manufacture of ophthalmic implants by photopolymerization, containing: a) 60-70 wt.% urethane di(meth)acrylate oligomer with terminal (meth)acrylate fragments, consisting of the following components: (I) (meth)acrylate, (II) diisocyanate and (III) a polyol and having the following structure: hydroxy(meth)acrylate'-{(diisocyanate'-polyol-diisocyanate)}hydroxy(meth)acrylate, where one of the isocyanate groups of diisocyanate' and diisocyanate, respectively, is connected to hydroxy(meth) acrylate' and hydroxy(meth)acrylate'' to form a urethane bond, and where the remaining isocyanate group of the diisocyanate' and diisocyanate, respectively, is connected to the hydroxyl group of the polyol to form a urethane bond, where hydroxy(meth)acrylate' and hydroxy(meth)acrylate '' may be the same or different, and the diisocyanate' and diisocyanate may be the same or different, wherein the polyol in the urethane di(meth)acrylate oligomer may be any branched chain aliphatic diol, as well as be a mixture of several; b) 20-40% by weight of a component from the group of (meth)acrylate monomers with aromatic substituents in the side chain, comprising at least one of the following: 2-phenoxyethyl methacrylate, benzyl methacrylate, benzyl-2-ethyl acrylate, phenyl methacrylate; c) 5-25% by weight of a component from the group of (meth)acrylate monomers with aliphatic branched substituents in the side chain, comprising at least one of the following: tert-butyl me tacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate; d) not less than 0.2 wt.% polymerizable UV filter, including UV-absorbing compounds of the benzophenone or benzotriazole series, or a combination thereof; e) from 0.1 to 1 wt% of a photopolymerization initiator; e) from 0.005 to 0.5 wt.% of a radical polymerization inhibitor, including at least one of the following: 4-tert-butylpyrocatechol, tert-butylhydroquinone, 1,4-benzoquinone, 6-tert-butyl-2,4-xylenol, 2-tert-butyl-1,4-benzoquinone, 3,5-di-tert-butyl-o-benzoquinone, - 4 043007 2,6-di-tert-butyl-p-cresol, 2,6-di-tert-butylphenol, hydroquinone, 4-methoxyphenol.