Intraocular lens compositions

Abstract

To provide an intraocular lens composition that is completely vacuole-free, and a method for producing the composition.SOLUTION: The invention pertains to intraocular lens compositions comprising a polymeric mixture of monomers, a product comprising such compositions and uses thereof. The compositions of the inventions are completely vacuole-free, therefore resulting in a truly glistening free material. Moreover, they are soft enough to be easy to fold, have properly tuned hardness to provide a comfortable unfolding speed, require only low injection force, do not present excessive tackiness, and have good optical properties. Finally, the present intraocular lens compositions do not suffer from calcification.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention is in the field of intraocular lens compositions.

Background Art

[0002] An intraocular lens is a lens that can be implanted in the eye and serves as a substitute for or supplements the natural lens material in the function of providing vision. An intraocular lens can be implanted in the eye, for example, in the treatment of cataracts or myopia.

[0003] Cataracts affect the natural lens of the eye, causing the eye to become cloudy and vision to blur. In such cases, the natural lens may be replaced with an artificial lens, thereby restoring vision. In other conditions such as myopia, the intraocular lens may be placed on the natural lens to treat by changing the refractive power of the eye.

[0004] Intraocular lens materials are well known and there are many types commercially or experimentally available. Generally, intraocular lens materials are polymerized compositions of one or more monomers. Important properties of such materials are transparency and stability. An important aspect of stability is the tendency of the lens material to form vacuoles over time. Vacuoles are small inclusions within the polymeric lens material that contain water and are commonly referred to as glistening. Due to the difference in refractive index between the lens material and the water within the vacuoles, incident light diffracts and glare is generated, reducing vision.

[0005] Furthermore, the intraocular lens material must be sufficiently flexible to allow the lens to be folded. This is important during surgery where the lens is folded and placed within a cartridge, inserted through a small incision via a nozzle into the eye, and upon entry into the eye, the lens unfolds and returns to its original shape. However, the material must not be too soft to avoid the lens unfolding too quickly. Waiting too long for the lens to unfold during surgery is inefficient and can cause complications, but if the unfolding is too rapid, it can also damage the eye tissue. Thus, the unfolding time is an important property of the lens material. The tackiness of the material should be low so as not to impede the unfolding of the lens within the eye after insertion. When folding the lens and extruding it from the small nozzle of an injector of about 2 mm, the material needs to be tough enough to withstand the stress exerted during insertion; otherwise, the lens may break into two or more pieces or become deformed during insertion. Furthermore, even after the lens is inserted and returns to its original shape, the optical quality of the lens needs to be high.

[0006] Intraocular lens materials are generally hydrophobic or hydrophilic. Hydrophilic materials have the advantage of containing fewer vacuoles, but such materials generally suffer from calcification and become unusable after an unpredictable period of time. Hydrophobic materials are good in that they are not subject to calcification, but hydrophobic materials tend to generate vacuoles. This results in a lens material that becomes increasingly hazy over time. Furthermore, hydrophobic lens materials are generally more sticky and the tackiness can interfere with the unfolding of the lens or cause tactile parts to adhere to the optical components, potentially causing complications during the unfolding process. Known hydrophobic lens materials are often made harder to reduce hazing and lower the tackiness, but harder lens materials unfold slowly, reducing the efficiency of the process, making insertion difficult, and in some cases, even causing damage to the injector nozzle during surgery.

[0007] The present invention provides an intraocular lens composition without vacuoles, and thus improves known lens materials in that it provides a material without any glistening. Further, it is sufficiently soft so as to be easily foldable, has a hardness appropriately adjusted to provide a suitable unfolding speed, requires only a low insertion force, does not exhibit excessive adhesiveness, and has good optical properties. Further, the present intraocular lens composition is not vulnerable to calcification.

Brief Description of the Drawings

[0008]

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DETAILED DESCRIPTION OF THE INVENTION

[0009] The present invention is as described in claim 1. The present invention provides an intraocular lens composition comprising a polymer mixture of at least the following four different monomers: a short (meth)acrylate crosslinking agent, a long (meth)acrylate crosslinking agent, one or more (meth)acrylate monomers of formula (I), and one or more Cl-C4-alkyl (meth)acrylates, or a combination of phenyl-Cl-C4-alkyl (meth)acrylate and cycloalkyl (meth)acrylate.

[0010] This composition provides an intraocular lens composition without any vacuoles, and thus has advantages over known compositions in that it provides a material without any glistening. Furthermore, it is sufficiently soft to be easily foldable, has a hardness appropriately adjusted to provide a suitable unfolding speed, requires only a low insertion force, does not exhibit excessive adhesiveness, and has good optical properties. Further, this intraocular lens composition is not prone to calcification.

[0011] The intraocular lens composition may be abbreviated as IOL. It is a polymeric intraocular lens composition based on at least the above monomers appropriately polymerized. In a preferred embodiment, the polymeric composition contains at least 50% by weight of the above monomers appropriately polymerized, based on the weight of the composition. In a preferred embodiment, the polymeric composition contains at least 60% by weight, preferably at least 70% by weight, more preferably at least 80% by weight of the above monomers appropriately polymerized.

[0012] The term "polymer mixture of monomers" is construed as well-known in the art and means that the monomers contained in the polymeric intraocular lens composition are polymerized to provide the intraocular lens composition of the present invention. In this context, "polymerized" means that at least 90%, generally more than 95%, and usually essentially all monomer molecules (e.g., at least 99% of all monomer molecules) are polymerized to give a polymeric intraocular lens composition. If the total residual content of unreacted monomers is more than desired, extraction with a suitable solvent to remove the unreacted monomers may be carried out as desired, as is well-known in the art.

[0013] Thus, the polymer mixture of monomers that is the intraocular lens composition is preferably a polymer composition that contains almost no monomers; rather, all the monomers used are incorporated into the polymer mixture during the polymerization reaction when preparing the intraocular lens composition. The polymer mixture of monomers contains almost no unreacted monomers.

[0014] The intraocular lens composition contains a polymer mixture of monomers and may further contain other conventional elements such as UV and / or blue light filter monomers as described in, for example, WO1995 / 011279A1.

[0015] In some preferred embodiments, the intraocular lens composition consists only of a polymer mixture, but may contain unavoidable impurities (e.g., impurities derived from the polymerization process, particularly residues and decomposition products derived from the polymerization initiator).

[0016] The essential monomer contained in the polymer composition is a (meth)acrylate monomer. The polymerization process for obtaining the intraocular lens composition must therefore be adapted to enable the polymerization of the (meth)acrylate monomer. In a preferred embodiment, the polymerization process is a radical polymerization process. Radical polymerization is well known in the art.

[0017] <Short crosslinking agent> The first essential monomer contained in the intraocular lens composition is a short crosslinking agent comprising two or more (meth)acrylate moieties and a linking moiety located between the two (meth)acrylate moieties, wherein the linking moiety is linked to the (meth)acrylate moiety via an ester group, and the longest chain of atomic sequence between the oxygen atom of the ester group linking the first (meth)acrylate moiety to the linking moiety and the oxygen atom of the ester group linking the second (meth)acrylate moiety to the linking moiety is 1 to 11 atoms. The short crosslinking agent can be represented by the following formula.

[0018]

Chemical formula

[0019] In this formula, R is H or CH3, and SC represents a short linking moiety.

[0020] The (meth)acrylate moieties of the short crosslinking agent may independently be acrylate moieties or methacrylate moieties. In a preferred embodiment, the short crosslinking agent comprises two acrylate moieties or two methacrylate moieties. Most preferably, the short crosslinking agent comprises two methacrylate moieties (dimethacrylate).

[0021] The linking moiety is linked to the (meth)acrylate moiety of the short crosslinking agent via an ester group, and this ester group is located at the carbonyl group of the (meth)acrylate.

[0022] The linking moiety is defined as the moiety that links two (meth)acrylate moieties via a covalently bonded atomic sequence. The longest chain-like atomic sequence of the short crosslinker extends between the oxygen atom of the ester group that links the first (meth)acrylate moiety to the linking moiety and the oxygen atom of the ester group that links the second (meth)acrylate moiety to the linking moiety, and is 1 to 11 atoms, preferably 1 to 8 atoms, more preferably 2 to 5 atoms. Thus, the short linking moiety is represented by a chain-like sequence of 1 to 11 atoms, 1 to 8 atoms, or 2 to 5 atoms.

[0023] The longest chain-like atomic sequence of the short crosslinker contains C atoms and optionally O atoms and / or N atoms, and the total number of C atoms exceeds the total number of O atoms and N atoms. In a preferred embodiment, the longest chain-like atomic sequence of the short crosslinker contains only C atoms (and optionally O atoms), and the total number of C atoms exceeds the total number when O atoms are present. In a highly preferred embodiment, the ratio of C atoms:O atoms is greater than 2:1.

[0024] The longest chain-like atomic sequence of the short crosslinker may contain side groups that do not significantly affect the reactivity of the (meth)acrylate moiety of the short crosslinker during the polymerization reaction. Preferably, the side group is R 2 , OR 2 , SR 2 , NR 2 2, COOR 2 , or F, and R 2 is H, alkyl, cycloalkyl, heterocycloalkyl, aromatic moiety, or any combination thereof, and R 2 has a molecular weight of up to 100 Da.

[0025] The short crosslinker may also contain more than two (meth)acrylate moieties, for example, three, four, or even more (meth)acrylate moieties.

[0026] In a highly preferred embodiment, the short crosslinking agent is ethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, butylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, dipropylene glycol di(meth)acrylate, dibutylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tripropylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, trimethylolpropane ethoxylate tri(meth)acrylate (having up to 1 unit of ethoxylate per arm), trimethylolpropane propoxylate tri(meth)acrylate (having up to 1 unit of propoxylate per arm), glycerol tri(meth)acrylate, pentaerythritol tri(meth)acrylate, glycerol ethoxylate tri(meth)acrylate (having up to 1 unit of ethoxylate per arm), glycerol propoxylate tri(meth)acrylate (having up to 1 unit of propoxylate per arm), pentaerythritol ethoxylate tetra(meth)acrylate (having up to 1 unit of ethoxylate per arm), pentaerythritol propoxylate tetra(meth)acrylate (having up to 1 unit of propoxylate per arm), di(trimethylolpropane) tetra(meth)acrylate, pentaerythritol tetra(meth)acrylate, dipentaerythritol penta(meth)acrylate, or dipentaerythritol hexa(meth)acrylate, preferably ethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, butylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, dipropylene glycol di( (Meth)acrylate, dibutylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tripropylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, glycerol tri(meth)acrylate, pentaerythritol tri(meth)acrylate, di(trimethylolpropane) tetra(meth)acrylate, pentaerythritol tetra(meth)acrylate, dipentaerythritol penta(meth)acrylate, or dipentaerythritol hexa(meth)acrylate, more preferably ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, propylene glycol di(meth)acrylate, tripropylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, di(trimethylolpropane) tetra(meth)acrylate, or pentaerythritol tetra(meth)acrylate.

[0027] In some embodiments, acrylate is preferred. In alternative preferred embodiments, methacrylate is preferred.

[0028] Preferably, the amount of the short crosslinking agent in the monomer mixture is 0.1 to 12% by weight, preferably 0.2 to 10% by weight, more preferably 0.5 to 8% by weight based on the total monomer mixture.

[0029] In some highly preferred embodiments, the amount of the short crosslinking agent in the monomer mixture is 0.1 to 3% by weight, preferably 0.1 to 2% by weight. In other highly preferred embodiments, the amount of the short crosslinking agent in the monomer mixture is 2 to 10% by weight, preferably 2 to 7% by weight.

[0030] <long crosslinking agent> The second essential monomer contained in the intraocular lens composition is a long crosslinking agent comprising two or more (meth)acrylate moieties and a linking moiety located between the two (meth)acrylate moieties, wherein the linking moiety is linked to the (meth)acrylate moiety via an ester group, and the longest chain of atoms between the oxygen atom of the ester group linking the first (meth)acrylate moiety to the linking moiety and the oxygen atom of the ester group linking the second (meth)acrylate moiety to the linking moiety is 14 atoms or more. The long crosslinking agent can be represented by the following formula.

[0031] [Chemical formula]

[0032] In this formula, R is H or CH3, and LC represents a long linking moiety.

[0033] The (meth)acrylate moieties of the long crosslinking agent may independently be acrylate moieties or methacrylate moieties. In a preferred embodiment, the long crosslinking agent comprises two acrylate moieties or two methacrylate moieties.

[0034] The linking moiety is linked to the (meth)acrylate moiety of the long crosslinking agent via an ester group, and this ester group is located at the carbonyl group of the (meth)acrylate.

[0035] The linking moiety is defined as the moiety that links the two (meth)acrylate moieties via a covalently bonded chain of atoms. The longest chain of atoms of the linking moiety of the long crosslinking agent extends between the oxygen atom of the ester group linking the first (meth)acrylate moiety to the linking moiety and the oxygen atom of the ester group linking the second (meth)acrylate moiety to the linking moiety, and is 12 atoms or more, preferably 15 atoms or more, more preferably 20 atoms or more. In a preferred embodiment, the long crosslinking agent has a longest chain of atoms of 100 atoms or less, preferably 80 atoms or more, more preferably 50 atoms or more, for example 30 atoms or less.

[0036] The longest chain of atoms of the long crosslinker contains C atoms and optionally O atoms and / or N atoms, with the total number of C atoms exceeding the total number of O and N atoms. In a preferred embodiment, the longest chain of atoms of the long crosslinker contains only C atoms (and optionally O atoms), and the total number of C atoms exceeds the total number if O atoms are present. In a highly preferred embodiment, the ratio of C atoms:O atoms is greater than 2:1.

[0037] The longest chain of atoms of the long crosslinker may contain side groups that do not significantly affect the reactivity of the (meth)acrylate moiety of the long crosslinker during the polymerization reaction. Preferably, the side groups are R 2 , OR 2 , SR 2 , NR 2 2, COOR 2 , or F, where R 2 is H, alkyl, cycloalkyl, heterocycloalkyl, an aromatic moiety, or any combination thereof, and R 2 has a molecular weight of up to 100 Da.

[0038] The long crosslinker may also contain more than two (meth)acrylate moieties, for example, three, four, or even more (meth)acrylate moieties. Such long crosslinkers may be referred to as "star-shaped" long crosslinkers.

[0039] In a highly preferred embodiment, the long crosslinking agent is poly(ethylene glycol) di(meth)acrylate, poly(propylene glycol) di(meth)acrylate, poly(butylene glycol) di(meth)acrylate, poly(pentylene glycol) di(meth)acrylate, trimethylolpropane ethoxylate tri(meth)acrylate (having an ethoxylate unit sufficient to form a linking moiety of 12 atoms or more), trimethylolpropane propoxylate tri(meth)acrylate (having a propoxylate unit sufficient to form a linking moiety of 12 atoms or more), glycerol ethoxylate tri(meth)acrylate (having an ethoxylate unit sufficient to form a linking moiety of 12 atoms or more), glycerol propoxylate tri(meth)acrylate (having a propoxylate unit sufficient to form a linking moiety of 12 atoms or more), pentaerythritol ethoxylate tetra(meth)acrylate (having an ethoxylate unit sufficient to form a linking moiety of 12 atoms or more), pentaerythritol propoxylate tetra(meth)acrylate (having a propoxylate unit sufficient to form a linking moiety of 12 atoms or more), preferably poly(ethylene glycol) di(meth)acrylate, poly(propylene glycol) di(meth)acrylate, trimethylolpropane ethoxylate tri(meth)acrylate (having an ethoxylate unit sufficient to form a linking moiety of 12 atoms or more), or trimethylolpropane propoxylate tri(meth)acrylate (having a propoxylate unit sufficient to form a linking moiety of 12 atoms or more).

[0040] In some embodiments, acrylate is preferred. In alternative preferred embodiments, methacrylate is preferred.

[0041] In a preferred embodiment, the long crosslinking agent has a molecular weight of 340 to 5000 Da, preferably 346 to 3000 Da, more preferably 350 to 1500 Da, and most preferably 400 to 1000 Da.

[0042] Preferably, the amount of the long crosslinking agent in the monomer mixture is 0.5 to 25% by weight, preferably 1 to 25% by weight, more preferably 2 to 20% by weight, and still more preferably 2 to 10% by weight based on the total monomer mixture.

[0043] In some highly preferred embodiments, the amount of the long crosslinking agent in the monomer mixture is 1 to 15% by weight, preferably 2 to 12% by weight. In other highly preferred embodiments, the amount of the long crosslinking agent in the monomer mixture is 1 to 20% by weight, preferably 7 to 18% by weight.

[0044] <One or more (meth)acrylate monomers of formula (I)> The third essential monomer contained in the polymer intraocular lens composition is one or more (meth)acrylate monomers of the following formula (I).

[0045]

Chemical formula

[0046] Here, X is -(C1-C4 alkyl)-O-, -(C1-C4 alkyl)-S-, -(C1-C4 alkyl)-N- or a C1-C8 alkyl group, wherein the C1-C8 alkyl group contains cycloalkyl and one of the C atoms is substituted with a heteroatom selected from the group consisting of O, S and N, Y is absent or -C1-C4 alkyl, n is 1 to 6, R is H or CH3.

[0047] In formula (I), the alkyl moieties in X and Y may be linear, branched or cyclic, preferably linear. Optionally, the alkyl moieties may be substituted with a group that does not affect the reactivity of the (meth)acrylate moiety, such as a fluoro group. In a preferred embodiment, X is -(C1-C4 alkyl)-O- or (C1-C4 alkyl)-S-, more preferably, X is -(C1-C4 alkyl)O-. In a preferred embodiment, n is 1 or 2.

[0048] In a preferred embodiment, the (meth)acrylate monomer of formula (I) is methoxymethyl (meth)acrylate, methoxyethyl (meth)acrylate, methoxypropyl (meth )acrylate, methoxybutyl (meth)acrylate, ethoxymethyl (meth)acrylate, ethoxyethyl (meth)acrylate, ethoxypropyl (meth)acrylate, ethoxybutyl (meth)acrylate, propyloxymethyl (meth)acrylate, propyloxyethyl (meth)acrylate, propyloxypropyl (meth)acrylate, propyloxybutyl (meth)acrylate, butoxymethyl (meth)acrylate, butoxyethyl (meth)acrylate, butoxypropyl (meth)acrylate or butoxybutyl (meth)acrylate. In some embodiments, acrylate is preferred. In alternative preferred embodiments, methacrylate is preferred.

[0049] In a more preferred embodiment, the (meth)acrylate monomer of formula (I) is methoxyethyl (meth)acrylate, methoxypropyl (meth)acrylate, ethoxyethyl (meth)acrylate, methoxyethoxyethyl (meth)acrylate, di(ethylene glycol) ethyl ether (meth)acrylate or triethylene glycol methyl ether (meth)acrylate or ethoxypropyl (meth)acrylate, or propyloxyethyl (meth)acrylate.

[0050] In a highly preferred embodiment, the (meth)acrylate monomer of formula (I) is methoxyethyl acrylate or methoxyethyl methacrylate. Most preferably, one or more (meth)acrylate monomers of formula (I) include methoxyethyl methacrylate, methoxyethyl acrylate, ethoxyethyl methacrylate, ethoxyethyl acrylate, methoxyethoxyethyl methacrylate, methoxyethoxyethyl acrylate, di(ethylene glycol) ethyl ether acrylate, and triethylene glycol methyl ether methacrylate. In some embodiments, a mixture of methacrylate and acrylate of the same (meth)acrylate monomer of formula (I) is preferred. In some preferred embodiments, a mixture of methoxyethyl acrylate and methoxyethyl methacrylate is preferred.

[0051] In a preferred embodiment, the (total) amount of one or more (meth)acrylate monomers of formula (I) in the monomer mixture is 15 to 90% by weight, preferably 18 to 85% by weight.

[0052] In some highly preferred embodiments, the total amount of the (meth)acrylate monomer of formula (I) in the monomer mixture is 35 to 90% by weight, preferably 42 to 83% by weight, based on the total monomer mixture. In other highly preferred embodiments, the amount of the (meth)acrylate monomer of formula (I) in the monomer mixture is 15 to 55% by weight, preferably 18 to 45% by weight.

[0053] <Fourth monomer> The fourth essential monomer in the polymer intraocular lens composition is either one or more C1-C4-alkyl (meth)acrylates, or a combination of phenyl-C1-C4-alkyl (meth)acrylates and cycloalkyl (meth)acrylates. The total amount of the alkyl (meth)acrylate, or the combination of phenylalkyl (meth)acrylate and cycloalkyl (meth)acrylate, is preferably 5 to 70% by weight, more preferably 5 to 35% by weight, based on the total monomer mixture.

[0054] <One or more C1-C4-alkyl (meth)acrylates> One or more C1-C4-alkyl (meth)acrylates can be represented by the following formula II.

[0055] [Chemical formula]

[0056] Here, Y is -C1-C4 alkyl, R is H or CH3.

[0057] In formula II, the alkyl part of Y may be linear, branched or cyclic, preferably linear. Optionally, the alkyl part may be substituted with a group that does not affect the reactivity of the (meth)acrylate part, such as a fluoro group.

[0058] In a preferred embodiment, the C1-C4-alkyl (meth)acrylate is methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate such as n-propyl or isopropyl (meth)acrylate, or butyl (meth)acrylate such as n-butyl, sec-butyl, isobutyl, tert-butyl or cyclobutyl-(meth)acrylate. Among these (meth)acrylates, methacrylate is preferred. In a particularly preferred embodiment, the C1-C4-alkyl (meth)acrylate is methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate or tert-butyl (meth)acrylate, preferably methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate or tert-butyl acrylate, and most preferably methyl methacrylate, ethyl methacrylate, propyl methacrylate or butyl methacrylate.

[0059] The amount of Cl-C4-alkyl (meth)acrylate in the monomer mixture, if present, is preferably 5 to 75% by weight, more preferably 15 to 70% by weight, based on the total monomer mixture.

[0060] <Phenyl-C1-C4-alkyl (meth)acrylate> Phenyl-Cl-C4-alkyl (meth)acrylate, if present, is of the following formula (III).

[0061] [Chemical formula]

[0062] Here, X is absent or -C1-C4 alkyl, R is H or CH3.

[0063] In formula III, the phenyl moiety may optionally be substituted with a group that does not affect the reactivity of the (meth)acrylate moiety, such as a Cl-C6(cyclo)alkyl group, a C1-C6(cyclo)alkoxy group or a fluoro group.

[0064] In a preferred embodiment, the phenyl-Cl-C4-alkyl (meth)acrylate can be phenylmethyl (meth)acrylate (also referred to as benzyl (meth)acrylate), phenyl (meth)acrylate, 1-phenylethyl (meth)acrylate, 2-phenylethyl (meth)acrylate, 1-phenylpropyl (meth)acrylate, 2-phenylpropyl (meth)acrylate, 3-phenylpropyl (meth)acrylate, phenylcyclopropyl (meth)acrylate, 1-phenylbutyl (meth)acrylate, 2-phenylbutyl (meth)acrylate, 3-phenylbutyl (meth)acrylate, 4-phenylbutyl (meth)acrylate or phenylcyclobutyl (meth)acrylate.

[0065] In a highly preferred embodiment, the phenyl-Cl-C4-alkyl (meth)acrylate is phenyl (meth)acrylate, phenylmethyl (meth)acrylate, phenylethyl (meth)acrylate.

[0066] When present, the amount of phenyl-Cl-C4-alkyl (meth)acrylate in the monomer mixture is preferably 5 to 40% by weight, more preferably 8 to 33% by weight, based on the total monomer mixture.

[0067] <Cycloalkyl (meth)acrylate> When present, the cycloalkyl (meth)acrylate is of the following formula (IV).

[0068]

Chemical formula

[0069] Here, X is absent, a C1-C5 alkyl group, or a -[(C1-C4 alkyl)-O]n- group (n is 1 to 8), Y is a C3-C18 alkyl group containing at least one cycloalkyl moiety, said C3-C18 alkyl group optionally containing one or more heteroatoms selected from the group of O and N, R is H or CH3.

[0070] In formula IV, the alkyl moiety of X may be linear, branched or cyclic, preferably linear. Optionally, the alkyl moiety may be substituted with a group that does not affect the reactivity of the (meth)acrylate moiety, such as a fluoro group.

[0071] Preferably, X is absent, methylene, ethylene, propylene, butylene or pentylene, more preferably X is absent, methylene or ethylene. Most preferably, X is absent.

[0072] Y is a C3-C18 alkyl group containing at least one cycloalkyl moiety, and optionally, one or more C atoms of said alkyl group may be substituted by an O atom and / or an N atom, preferably an O atom. Thus, the total number of C atoms, O atoms and / or N atoms in the group does not exceed 18. The O atom and N atom, if present, are preferably not located in the cycloalkyl moiety.

[0073] Preferably, Y contains a monocyclic ring system such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc., or a bicyclic or tricyclic alkyl group containing any combination of these monocyclic systems. Particularly preferred bicyclic or tricyclic systems are norbornyl, isobornyl, or adamantyl.

[0074] Y may further contain a linear or branched alkyl moiety (which may contain heteroatoms O and / or N) located between X and the cycloalkyl moiety. Optionally, the cycloalkyl moiety may be further substituted by an alkyl group, a fluoro group, a hydroxyl (OH) group or an amino (NH2) group, or may also be an alkyl-substituted derivative of an amino- or hydroxy-substituted cycloalkyl moiety (i.e., an ether or a secondary or tertiary amine).

[0075] In a preferred embodiment, Y is a cycloalkyl group, more preferably a C3-C10 cycloalkyl group.

[0076] In a highly preferred embodiment, the cycloalkyl (meth)acrylate is cyclopentyl (meth)acrylate, cyclohexyl (meth)acrylate, cycloheptyl (meth)acrylate, norbornyl (meth)acrylate, isobornyl (meth)acrylate or adamantyl (meth)acrylate. Among these, methacrylate is preferred. Alternatively, acrylate is preferred.

[0077] The amount of cycloalkyl (meth)acrylate in the monomer mixture, if present, is preferably 10 to 55% by weight, more preferably 14 to 45% by weight, based on the total monomer mixture.

[0078] <Any monomer in the monomer mixture> As described above, the polymer composition preferably contains at least 50% by weight of the above monomers polymerized appropriately, based on the weight of the composition. In a preferred embodiment, the polymer composition contains at least 60% by weight, preferably at least 70% by weight, more preferably at least 80% by weight of the above monomers polymerized appropriately. Other conventional monomers other than those listed above may thus be present to a considerable extent. These other conventional monomers can be selected from all conventional (meth)acrylic and vinyl monomers in the field of intraocular lenses and do not fall into any of the above essential categories.

[0079] In a preferred embodiment, the monomer mixture further contains an amount of a UV light filter chromophore ("UV blocker" or "UV filter"), preferably a methacrylate substituted with benzotriazole, suitable for absorbing at least 50%, preferably at least 75%, more preferably at least 85% of the light radiation having a wavelength of 350 to 400 nm. Examples of such UV filter chromophores are 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate (CAS 96478-09-0), and 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (CAS 16432-81-8).

[0080] If the composition contains a defined UV light filter chromophore, the amount of this monomer is preferably 0.1 to 2% by weight, preferably 0.2 to 1% by weight, more preferably 0.4 to 0.8% by weight of the monomer mixture.

[0081] In a more preferred embodiment, the monomer mixture further comprises an amount of a blue light filter chromophore ("blue light filter") suitable for absorbing at least 50%, preferably at least 75%, more preferably at least 85% of the light radiation having a wavelength of 400 - 500 nm. Examples of such blue light filter chromophores are the polymerizable yellow dyes described in WO1995 / 011279A1. When the composition contains a defined blue light filter chromophore, the amount of this monomer is preferably 0.1 - 2% by weight, preferably 0.2 - 1% by weight, more preferably 0.4 - 0.8% by weight of the monomer mixture.

[0082] <Preferred Embodiment> A preferred intraocular lens composition according to the present invention is: · 0.1 - 12% by weight, preferably 0.5 - 8% by weight of a short crosslinking agent; · 1 - 25% by weight, preferably 2 - 10% by weight of a long crosslinking agent; · 15 - 90% by weight, preferably 18 - 85% by weight of one or more (meth)acrylate monomers of formula (I); · 5 - 75% by weight, preferably 15 - 70% by weight of one or more C1 - C4 - alkyl (meth)acrylates of formula (II) (when present); · 5 - 40% by weight, preferably 8 - 33% by weight of phenyl - Cl - C4 - alkyl (meth)acrylates of formula (III) (when present); · 10 - 55% by weight, preferably 14 - 45% by weight of cycloalkyl (meth)acrylates of formula (IV) (when present); and · Optionally, 0.1 and 2% by weight of a UV light filter chromophore and / or 0.1 and 2% by weight of a blue light filter chromophore, wherein the % by weight is based on the total monomer mixture in the monomer mixture.

[0083] In a very preferred embodiment, the intraocular lens composition comprises a polymer mixture of the following monomers: · 15 to 90% by weight, preferably 18 to 85% by weight, of one or more (meth)acrylate monomers of formula (I); · 5 to 75% by weight, preferably 15 to 70% by weight, of one or more C1-C4-alkyl (meth)acrylates of formula (II); · 1 to 25% by weight, preferably 2 to 10% by weight, of a long crosslinking agent; · 0.1 to 12% by weight, preferably 0.5 to 8% by weight, of a short crosslinking agent.

[0084] Such a mixture is referred to as Embodiment A. In a highly preferred embodiment, the UV light filter chromophore and / or blue light filter chromophore as defined above are included in Embodiment A.

[0085] In an alternative highly preferred embodiment, the intraocular lens composition comprises a polymer mixture of the following monomers: · 15 to 90% by weight, preferably 18 to 85% by weight, of one or more (meth)acrylate monomers of formula (I); · 5 to 40% by weight, preferably 8 to 33% by weight, of phenyl-Cl-C4-alkyl (meth)acrylates of formula (III); · 10 to 55% by weight, preferably 14 to 45% by weight, of cycloalkyl (meth)acrylates of formula (IV) · 1 to 25% by weight, preferably 2 to 10% by weight, of a long crosslinking agent; · 0.1 to 12% by weight, preferably 0.5 to 8% by weight, of a short crosslinking agent.

[0086] Such a mixture is referred to as Embodiment B. In a highly preferred embodiment, the UV light filter chromophore and / or blue light filter chromophore as defined above are included in Embodiment B.

[0087] A more preferred composition according to the present invention comprises a polymer mixture of the monomers of Examples 1 to 13. For each of the exemplary compositions of Examples 1 to 13, the monomers listed may be present in amounts slightly deviated from the amounts of the monomers used in the examples. The slight deviation here means that the amount of the monomer can be from 5 wt% less than the amount shown in the example to 5 wt% more, preferably from 2 wt% less than the exemplary amount to 2 wt% more, more preferably from 1 wt% less than the amount to 1 wt% more, and even more preferably from 0.5 wt% less than the amount to 0.5 wt% more. Therefore, for each lens composition according to the present invention in the examples, the monomers listed may be present at the listed amount ±5 wt%, preferably ±2 wt%, more preferably ±1 wt%, and most preferably ±0.5 wt%. Such slight deviations do not affect the properties of the resulting lens. The present invention thus provides a lens material characterized by the individual examples according to the present invention.

[0088] <Properties of this polymer composition> The intraocular lens composition defined in this specification does not contain any vacuoles. This distinguishes this composition from the compositions of the prior art. In the prior art, the tendency of the composition to gradually form vacuoles is determined by aging the composition at a specific temperature for a specific time. The general aging temperatures published in the literature are, for example, 37 °C or 40 °C (for example, in WO2015084788A1 and US8449610B2, the aging temperature is 45 °C for 1 day, followed by room temperature for 1 to 2 hours; in EP1857477B1, a temperature of 33 °C is adopted; in Biomedical Optic Express, 4, 8, 2013, 1294 - 1304, a temperature of 35 °C for 8 hours is adopted; in J Cataract Refract Surg 2004, 30, 1768 - 1772, a maximum temperature of 41 °C is adopted; in WO2012106118A2, a temperature of 50 °C is adopted (however, the test pieces are inspected without steps at room temperature)); the aging time is, for example, 1 day or several hours. In the prior art experiments on vacuole formation, the aging temperature was never raised above 50 °C and was subsequently cooled to room temperature. The general aging temperatures published in the literature are, for example, 37 °C or 40 °C (for example, in WO2015084788A1 and US8449610B2, the aging temperature is 45 °C for 1 day, followed by room temperature for 1 to 2 hours; in EP1857477B1, a temperature of 33 °C is adopted; in Biomedical Optic Express, 4, 8, 2013, 1294 - 1304, a temperature of 35 °C for 8 hours is adopted; in J Cataract Refract Surg 2004, 30, 1768 - 1772, a maximum temperature of 41 °C is adopted; in WO2012106118A2, a temperature of 50 °C is adopted (however, the test pieces are inspected without steps at room temperature)); the aging time is, for example, 1 day or several hours. In the prior art experiments on vacuole formation, the aging temperature was never raised above 50 °C and was subsequently cooled to room temperature.

[0089] Aging of the composition at higher temperatures is known and accepted to reproduce the accelerated aging process under in vivo conditions. Thus, by aging at higher temperatures, the tendency of the material after years of use to form vacuoles can be reproduced in a much shorter period. This test consists of aging the composition in 0.9% aqueous NaCl solution at 50 °C for 16 hours or more. These conditions are significantly more severe than those previously carried out in the art, and therefore this method is much more accurate in showing vacuole formation after long-term use in vivo.

[0090] Comparison using these standardized and more severe test conditions for various known intraocular lens compositions shows that the known compositions are prone to vacuole formation and / or haze formation. However, this composition remains completely free of vacuoles even when using the above more severe test conditions. From the fact that vacuole formation is completely prevented, this composition is very suitable for use as a foldable and implantable ophthalmic device in ophthalmic surgery such as the treatment of cataract and refractive correction surgery (for example, the treatment of myopia).

[0091] The intraocular lens composition defined herein preferably has a water absorption of less than 10% by weight, more preferably less than 5% by weight. The water absorption can be measured by weight according to the following procedure: A certain amount of lenses (usually 10 - 20) are completely hydrated and their weights are measured. Next, the lenses are dried in a vacuum oven until their weights are stable. Subsequently, the water absorption (%) is measured according to the formula (W wet -W dry ) / W dry *100% [where W wet is the weight of the hydrated lenses (the hydrated lenses are of course dried from the residual water on their surfaces), and W dry is the weight of the lenses after being completely dried in a vacuum oven].

[0092] The intraocular lens composition defined in this specification has adhesiveness within the range required for application to intraocular surgery. The adhesiveness can be evaluated by folding a test piece shaped like a flying disc with an optical portion of about 6 mm and a diameter of about 14 mm of the planar parallel flap periphery with a thickness of about 0.35 mm (see Fig. 9) into two, and applying pressure with a finger for 1 second or 2 seconds or longer so that half of the flap of the test piece contacts and presses against the other half of the test piece. Then, the pressure is released. The non-adhesive test piece immediately begins to return to its original shape, while the adhesive test piece remains folded because the interaction between the two halves of the lens is too strong for the lens to unfold. Furthermore, and most importantly, no deployment due to adhesiveness was observed when the completed lens of this formulation was subjected to an insertion test using an injector with a 2.2 mm nozzle and a viscoelastic medium.

[0093] The intraocular lens compositions defined in this specification are soft enough to be easily foldable. They have a deployment time of 1 to 150 seconds, preferably 3 to 120 seconds, more preferably 5 to 30 seconds. After the lens passes through the injector nozzle and is placed in a small water bath at 26°C (simulating surgical conditions), the deployment time can be determined by recording a video of the lens, so that the deployment process can be accurately observed and timed.

[0094] The present invention thus also provides an intraocular lens, a corneal prosthesis, a corneal ring, a corneal implant, or a corneal inlay, comprising the intraocular lens composition as defined above.

[0095] <Method for producing an intraocular lens composition> This intraocular lens composition can be prepared by a generally known polymerization process using a mixture of the monomers as defined above as the starting mixture for polymerization. In a preferred embodiment, the polymerization process is a radical polymerization process. In a more preferred embodiment, the polymerization is carried out in a single step using a mixture of monomers as the reactants. As is known in the art, the mixture of monomers may contain a solvent if suitable. However, preferably, the polymer mixture consists only of the monomers to be polymerized and a polymerization initiator.

[0096] Thus, the present invention also relates to a method for preparing the intraocular lens composition as defined above, the method comprising 1) preparing a mixture of the monomers as defined above; 2) preferably adding a radical polymerization initiator; 3) polymerizing; 4) optionally, performing extraction using a suitable solvent to remove residual unreacted monomers or other impurities; and including.

[0097] Suitable polymerization initiators are radical polymerization initiators. Such compounds are well known and any compound known for this purpose can be used. Preferably, the initiator is, for example, a diazo initiator such as 2,2-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(2-methylpropionitrile), azobisisobutyronitrile, lauroyl peroxide, benzoyl peroxide, and also, for example, a photoinitiator such as phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide can be used. More preferably, the initiator is an organic peroxide such as di-t-butyl peroxide, benzoyl peroxide, lauroyl peroxide or methyl ethyl ketone peroxide.

[0098] The amount of the initiator depends on the types of the initiator and the monomer mixture, as known to those skilled in the art. Generally, when expressed as a weight percentage of the monomer mixture, the amount of the initiator can be 0.1 to 2% by weight, preferably 0.2 to 1.5% by weight, more preferably 0.5 to 1% by weight.

[0099] In certain embodiments, it is necessary to reduce the atmospheric content of oxygen prior to polymerization. However, in other embodiments of the present composition, polymerization can be carried out in an atmosphere containing oxygen, such as air. This is advantageous as it does not require the use of an inert atmosphere as in the prior art. The polymerization of the present composition can be carried out, for example, in a gas atmosphere where oxygen is about 21%. Preferably, the polymerization is carried out in an atmosphere with an oxygen content of preferably less than 5%, most preferably less than 1%.

[0100] Alternatively, as known in the art, the polymerization can be carried out in an inert atmosphere. The inert atmosphere may contain nitrogen or argon (or a mixture thereof), or other known inert gas(es).

[0101] The polymerization is generally carried out in a mold formed of polypropylene or other suitable material, and provides the shape and optical part of a lens, obtained or made in the form of a sheet or button of a thickness sufficient to form a lens by the latest known common race cut technique.

[0102] Suitably, after the polymerization is completed, the obtained polymer composition can be removed from the mold and cut, if desired, to form the haptic part of the lens. Once completed, the lens is dried or hydrated in an aqueous system and stored appropriately.

[0103] For the purposes of clarification and concise description, each feature is described herein as part of the same or separate embodiments. However, it should be understood that the scope of the present invention may include embodiments having combinations of all or some of the features described. Hereinafter, the present invention will be described by the following non-limiting examples.

[0104] <Example according to the present invention> Examples 1 to 13 show the components of the composition according to the present invention.

[0105] Example 1: Component Weight % Phenyl methacrylate 21.8 Cyclohexyl acrylate 28.8 Di(ethylene glycol) ethyl ether acrylate 38.1 Poly(ethylene glycol 700) diacrylate 7.0 Trimethylolpropane triacrylate 4.4

[0106] Example 2: Component Weight % Butyl methacrylate 68.4 Di(ethylene glycol) ethyl ether acrylate 19.9 Poly(ethylene glycol 700) diacrylate 7.8 Tri(propylene glycol) diacrylate 3.9

[0107] Example 3: Component Weight % Benzyl acrylate 15.5 Isobornyl methacrylate 29.5 Di(ethylene glycol) ethyl ether acrylate 44.7 Poly(ethylene glycol 1000) dimethacrylate 6.2 Ethylene glycol dimethacrylate 4.1

[0108] Example 4: Component Weight % Ethyl methacrylate 30.0 2-Methoxyethyl acrylate 51.8 2-Methoxyethyl methacrylate 8.5 Poly(ethylene glycol 400) diacrylate 4.8 Ethylene glycol dimethacrylate 4.8

[0109] Example 5: Component Weight % Benzyl methacrylate 30.6 Cyclohexyl acrylate 14.9 Di(ethylene glycol) methyl ether methacrylate 48.0 Poly(ethylene glycol 1000) dimethacrylate 4.4 Trimethylolpropane trimethacrylate 2.1

[0110] Example 6: Component Weight % Propyl methacrylate 21.7 2-(2-Methoxyethoxy)ethyl methacrylate 70.2 Poly(propylene glycol 800) diacrylate 5.4 Trimethylolpropane trimethacrylate 2.7

[0111] Example 7: Component Weight % 2-Phenylethyl acrylate 10.0 Cyclohexyl methacrylate 33.1 2-Methoxyethyl acrylate 45.4 Poly(ethylene glycol 400) diacrylate 8.0 Ethylene glycol dimethacrylate 3.5

[0112] Example 8: Component Weight % tert-Butyl acrylate 52.4 Tetrahydrofurfuryl acrylate 35.1 Poly(ethylene glycol 700) diacrylate 9.4 Tri(ethylene glycol) dimethacrylate 3.1

[0113] Example 9: Component Weight % Benzyl acrylate 16.7 1-Adamantyl methacrylate 25.0 Triethylene glycol methyl ether methacrylate 36.7 2-Ethoxyethyl methacrylate 16.7 Poly(ethylene glycol 600) diacrylate 2.5 Trimethylolpropane triacrylate 2.5

[0114] Example 10: Component Weight % Ethyl methacrylate 22.2 2-Methoxyethyl acrylate 23.0 2-Ethoxyethyl methacrylate 44.0 Poly(ethylene glycol 550) dimethacrylate 8.6 Tetra(ethylene glycol) dimethacrylate 2.2

[0115] Example 11: Component Weight % 2-Phenylethyl methacrylate 26.9 Isobornyl methacrylate 14.4 2-Methoxyethyl acrylate 48.3 Poly(ethylene glycol 400) diacrylate 6.7 Ethylene glycol dimethacrylate 3.6

[0116] Example 12: Component Weight % Methyl methacrylate 26.5 2-(2-Methoxyethoxy)ethyl methacrylate 65.3 Poly(propylene glycol 800) diacrylate 4.1 Tetra(ethylene glycol) diacrylate 4.1

[0117] Example 13: Component Weight % 2-Phenylethyl acrylate 8.3 1-Adamantyl methacrylate 30.3 2-Methoxyethyl acrylate 15.9 Di(ethylene glycol) ethyl ether acrylate 34.6 Poly(ethylene glycol 550) dimethacrylate 8.2 Di(ethylene glycol) dimethacrylate 2.7

[0118] The components were mixed together and stirred at room temperature until homogeneous. Subsequently, the mixture was filtered through a 0.45 μm inert filter and used to fill a mold formed of polypropylene or other suitable material.

[0119] Next, the filled mold was placed in an oven and the temperature was raised from room temperature (about 20 °C) to 90 °C over 5 hours, and then the temperature was maintained at 90 °C for an additional 6 hours to cure the polymer mixture. As will be understood by those skilled in the art, this heat profile can be varied depending on the mixture to adjust the results.

[0120] At this point, the molds were cooled to room temperature, then opened and the pieces were recovered. Depending on the type of mold, further machining, such as routing and milling, may be performed as is known in the art. Extraction of residual unreacted monomers may also be considered.

[0121] <Comparative Example> Examples 14 - 17 show compositions outside the scope of the present invention that exhibit void formation or other problems.

[0122] Example 14: Component wt% Benzyl acrylate 16.5 Isobornyl methacrylate 31.4 Di(ethylene glycol) ethyl ether acrylate 47.6 Ethylene glycol dimethacrylate 4.4

[0123] Example 15: Component wt% Benzyl methacrylate 32.0 Cyclohexyl acrylate 15.6 Di(ethylene glycol) methyl ether methacrylate 50.2 Trimethylolpropane trimethacrylate 2.1

[0124] Example 16: Component Weight % Butyl methacrylate 74.2 Di(ethylene glycol) ethyl ether acrylate 21.6 Tri(propylene glycol) diacrylate 4.2

[0125] Example 17: Component Weight % Ethyl methacrylate 21.0 2-Methoxyethyl acrylate 26.3 2-Ethoxyethyl methacrylate 50.3 Tetra(ethylene glycol) dimethacrylate 2.5

[0126] Example 18: Component Weight % Benzyl acrylate 17.1 1-Adamantyl methacrylate 25.6 Triethylene glycol methyl ether methacrylate 37.7 2-Ethoxyethyl methacrylate 17.1 Poly(ethylene glycol 600) diacrylate 2.6

[0127] The lenses were prepared from these compositions according to the same procedure as described above for Examples 1 to 13.

[0128] The present invention provides an intraocular lens composition that improves known lens materials, has no vacuoles even under severe test conditions, has a hardness appropriately adjusted to provide a moderate unfolding speed, ease of folding, and a moderate insertion force, and does not exhibit excessive adhesiveness. Furthermore, the refractive index (RI) is within the allowable values in all cases, and the optical quality (MTF) is consistently very good.

[0129] <Grisning test> The Grisning test is carried out by putting the lens into a 7 ml vial filled with 0.9% NaCl aqueous solution, maintaining the vial at 50 °C for 16 hours or more, cooling it at room temperature (20 °C) in about 0.5 to 1 hour, taking the lens out of the vial, and analyzing it with a microscope (Olympus BX50) under dark field illumination at magnifications of 20 times to 100 times, and up to 500 times as needed. In the microscope, micro-illumination method was used and no additional filter was added. The formation of vacuoles is visually evaluated.

[0130] The results for the lenses of Examples 1 to 13 are shown in FIGS. 1 to 13. It can be seen that no vacuoles were observed in these lenses prepared according to the present invention. The results of the Grisning test are summarized in Table 1 together with other parameters.

[0131] The lenses of Examples 14 to 18 are outside the scope of the present invention. Vacuoles exist in the lenses of Examples 14 to 17; the lens of Example 18 turns white after hydration in water and already has a few vacuoles before the Grisning test is carried out. These results are summarized in Table 2.

[0132] For comparison, the following commercially available lenses were used to conduct the Grisning test.

[0133] · AcrySof® (Alcon) · iSert® 255 (HOYA Surgical Optics) · Avansee™ (Kowa Pharmaceutical Europe) · Tecnis® (Johnson & Johnson Surgical Vision) · Asqelio™ (AST Products)

[0134] The results are shown in FIGS. 14 to 18 and summarized in Table 3. In the Alcon AcrySof (Figure 14), Hoya 255 (Figure 15), and Tecnis (Figure 17) lenses, many vacuoles are seen. The cloudy appearance of the Avansee lens (Figure 16) after the glistening test may be due to the formation of innumerable very small vacuoles. Water droplets that remained were seen in the 100x photographs but were not forcibly removed so as not to affect the glistening inside the material. Vacuoles are also seen in the Asqelio lens (Figure 18). Water droplets that remained were seen in the 100x photographs but were not forcibly removed so as not to affect the glistening inside the material.

[0135]

Table 1

[0136] Expansion speed: Measured after injecting into a water bath at 26°C (using an injector tip with a diameter of 2.2 mm; all lenses were injected using ophthalmic viscosurgical device). Adhesiveness: Based on the observation of a test piece folded into two like a flying disc; however, none of the lenses during the test could not expand after injection, and in all cases, the adhesiveness can be regarded as very low. RI: Measured using a refractometer of Index Instrument Limited, model CRL 12 - 70, at room temperature using a wavelength of 589 nm (all samples were hydrated in deionized water except for Example 13 hydrated in 0.9% NaCl aqueous solution). MTF was measured by PMTF by Lamda - X (all samples were hydrated in deionized water except for Example 13 hydrated in 0.9% NaCl aqueous solution).

[0137]

Table 2

[0138]

Table 3

[0139] <Additional Comparative Example>

[0140]

Table 4

[0141]

Table 5

[0142] Examples 19 and 20 represent a comparison with the products from US6140438. Examples 4 and 6 of US6140438 were reproduced as shown in that document. The polymerizable components specified in Tables 19 and 20 and, as a polymerization initiator, 1 part by weight of 2,2'-azobis(2,4-dimethylvaleronitrile) per 100 parts by weight of the total amount of the polymerizable components were mixed, and the mixture was poured into a casting mold having a desired intraocular lens shape. This casting mold was placed in an oven and subjected to thermal polymerization molding at 50°C for 24 hours. Subsequently, the casting mold was transferred to an air circulation dryer and heated from 65°C to 130°C at a rate of 10°C / hour, and then cooled to room temperature. Subsequently, LED black light irradiation was performed for 1 hour by using an irradiation device. Subsequently, the obtained polymer was taken out from the casting mold and further dried in an oven at 50°C for 2 days.

[0143] The lens compositions prepared in the same manner were subjected to the curing procedures described for Examples 1 to 13 instead of the curing procedure described in US6140438. The results were the same for both curing procedures.

[0144] The glazing test was carried out using the severe method described for Examples 1 to 13. The results for each of the lenses of Examples 19 and 20 are shown in Figures 20 to 21 and summarized in Table 4.

[0145]

Table 6

[0146] As shown in Table 4, the lens material prepared from the intraocular lens composition according to US6140438 contains vacuoles and is cloudy when observed under LED light. Thus, even though the lens of US6140438 is said to be free of vacuoles under the mild conditions and short time frame applied in US6140438, harsher conditions that reproduce the accelerated aging process under in vivo conditions indicate that the lens of US6140438 actually does have vacuoles and causes haze. Therefore, the lens material according to US6140438 shows very poor performance compared to the lens material according to the present invention that does not show vacuoles and turbidity.

Claims

1. An intraocular lens composition comprising a polymer mixture of the following monomers: a short crosslinker comprising two or more (meth)acrylate moieties and a linking moiety located between two of said (meth)acrylate moieties, said linking moiety being linked to said (meth)acrylate moieties via an ester group, the longest chain of atoms between an oxygen atom of an ester group linking a first (meth)acrylate moiety to said linking moiety and an oxygen atom of an ester group linking a second (meth)acrylate moiety to said linking moiety being 1 to 11 atoms; a long crosslinker comprising two or more (meth)acrylate moieties and a linking moiety located between two of said (meth)acrylate moieties, said linking moiety being linked to said (meth)acrylate moieties via an ester group, the longest chain of atoms between an oxygen atom of an ester group linking a first (meth)acrylate moiety to said linking moiety and an oxygen atom of an ester group linking a second (meth)acrylate moiety to said linking moiety being 12 atoms or more; one or more (meth)acrylate monomers of formula (I): 【Chemistry 1】 [Where: X is -(C1-C4 alkyl)-O-, -(C1-C4 alkyl)-S-, -(C1-C4 alkyl)-N- or a C1-C8 alkyl group, said C1-C8 alkyl group including cycloalkyl, one of the C atoms being replaced by a heteroatom selected from the group of O, S and N; Y is absent or -C1-C4 alkyl; n is 1 to 6; R is H or CH ３ It is. one or more Cl-C4-alkyl(meth)acrylate monomers of formula (II) below or a combination of at least one phenyl-Cl-C4-alkyl(meth)acrylate of formula (III) below with at least one cycloalkyl(meth)acrylate of formula (IV) below: 【Chemistry 2】 [Where: Y is -C1-C4 alkyl; R is H or CH ３ It is. 【Chemistry 3】 [Where: X is absent or -C1-C4 alkyl; R is H or CH ３ It is. 【Chemistry 4】 [Where: X is absent, a C1-C5 alkyl group, or a -[(C1-C4 alkyl)-O]n- group (n is 1 to 8); Y is a C3-C18 alkyl group containing at least one cycloalkyl moiety, said C3-C18 alkyl group optionally containing one or more heteroatoms selected from the group of O and N; R is H or CH ３ It is.

2. The longest chain of atoms defined for the long crosslinker and the short crosslinker includes C atoms, O atoms, and N atoms, the sum of C atoms exceeds the sum of O atoms and N atoms, and the chain of atoms is R ２ , OR ２ , S.R. ２ , N.R. ２ ２ , COOR ２ or F; R ２ is H, alkyl, cycloalkyl, heterocycloalkyl, aromatic moiety, or any combination thereof; R ２ The intraocular lens composition of claim 1 , wherein said intraocular lens composition has a molecular weight of up to 100 Da.

3. 3. An intraocular lens composition according to claim 1 or 2, wherein the amount of the short crosslinker is 0.1 to 12 wt. %, and / or the amount of the long crosslinker is 0.5 to 25 wt. %, and / or the amount of the one or more (meth)acrylate monomers of formula (I) is 10 to 90 wt. %, and / or the amount of the one or more Cl-C4-alkyl (meth)acrylate monomers of formula (II) or the combination of the phenyl-Cl-C4-alkyl (meth)acrylate of formula (III) and the cycloalkyl (meth)acrylate of formula (IV) is 5 to 70 wt. %, based on the total monomer mixture.

4. The short crosslinker is ethylene glycol di(meth)acrylate, or trimethylolpropane tri(meth)acrylate, or tetra(ethylene glycol) di(meth)acrylate. The intraocular lens composition according to any one of claims 1 to 3, comprising di(ethylene glycol) di(meth)acrylate, tri(propylene glycol) di(meth)acrylate, or tri(ethylene glycol) di(meth)acrylate.

5. The intraocular lens composition of any one of claims 1 to 4, wherein the long crosslinker comprises poly(ethylene glycol) di(meth)acrylate or poly(propylene glycol) di(meth)acrylate.

6. The intraocular lens composition of any one of claims 1 to 5, wherein the one or more (meth)acrylate monomers of formula (I) comprise di(ethylene glycol) ethyl ether acrylate, or 2-methoxyethyl acrylate, or 2-methoxyethyl methacrylate, or di(ethylene glycol) methyl ether methacrylate, or tetrahydrofurfuryl acrylate, or triethylene glycol methyl ether methacrylate, or mixtures thereof.

7. The intraocular lens composition according to any one of claims 1 to 6, wherein the one or more Cl-C4-alkyl (meth)acrylate monomers of formula (II) include butyl methacrylate, or ethyl methacrylate, or propyl methacrylate, or tert-butyl acrylate, or methyl methacrylate, or the phenyl-Cl-C4-alkyl (meth)acrylates of formula (III) include phenyl methacrylate, or benzyl acrylate, or benzyl methacrylate, or 2-phenylethyl acrylate, or 2-phenylethyl methacrylate, and the cycloalkyl (meth)acrylates of formula (IV) include cyclohexyl acrylate, or isobornyl methacrylate, or cyclohexyl methacrylate, or 1-adamantyl methacrylate, or isobornyl methacrylate.

8. The intraocular lens composition according to any one of claims 1 to 7, comprising a mixture of polymers: (a) 5 to 40% by weight, preferably 22±5% by weight, of phenyl methacrylate 10 to 55% by weight, preferably 29±5% by weight, of cyclohexyl acrylate 15 to 55% by weight, preferably 38±5% by weight, of di(ethylene glycol) ethyl ether acrylate 1-20% by weight, preferably 7±5% by weight, of poly(ethylene glycol) diacrylate having a molecular weight of 250-5000 Da, preferably 400-1000 Da 2 to 10% by weight, preferably 4±2% by weight, of trimethylolpropane triacrylate, or (b) 5 to 80% by weight, preferably 68±5% by weight, of butyl methacrylate 3 to 45% by weight, preferably 20±5% by weight, of di(ethylene glycol) ethyl ether acrylate 1-15% by weight, preferably 8±5% by weight, of poly(ethylene glycol) diacrylate having a molecular weight of 250-1800 Da, preferably 400-1000 Da 0.1 to 8% by weight, preferably 4±2% by weight, of tri(propylene glycol) diacrylate, or (c) 5 to 65% by weight, preferably 16±5% by weight, of benzyl acrylate 5 to 75% by weight, preferably 30±5% by weight, of isobornyl methacrylate 15 to 80% by weight, preferably 45±5% by weight, of di(ethylene glycol) ethyl ether acrylate 1-15% by weight, preferably 6±5% by weight, of 250-5000 Da, preferably 4 Poly(ethylene glycol) dimethacrylate having a molecular weight of 00 to 2500 Da 0.1 to 8% by weight, preferably 4±2% by weight, of ethylene glycol dimethacrylate, or (d) 1 to 60% by weight, preferably 30±5% by weight, of ethyl methacrylate 3 to 75% by weight of methoxyethyl acrylate and / or 2 to 85% by weight of methoxyethyl methacrylate, preferably 52±5% by weight of methoxyethyl acrylate and 9±5% by weight of methoxyethyl methacrylate 1-15% by weight, preferably 5±2% by weight, of poly(ethylene glycol) diacrylate having a molecular weight of 200-5000 Da, preferably 200-1000 Da 0.1 to 8% by weight, preferably 5±2% by weight, of ethylene glycol dimethacrylate, or (e) 5 to 75% by weight, preferably 31±5% by weight, of benzyl methacrylate 25 to 75% by weight, preferably 15±5% by weight, of cyclohexyl acrylate 15 to 80% by weight, preferably 48±5% by weight, of di(ethylene glycol) methyl ether methacrylate 1-15% by weight, preferably 4±2% by weight, of poly(ethylene glycol) dimethacrylate having a molecular weight of 250-5000 Da, preferably 400-1600 Da 0.1 to 8% by weight, preferably 2±1% by weight, of trimethylolpropane trimethacrylate, or (f) 1 to 65% by weight, preferably 22±5% by weight, of propyl methacrylate, 5 to 85% by weight, preferably 70±5% by weight, of 2-(2-methoxyethoxy)ethyl methacrylate 1-15% by weight, preferably 5±2% by weight, of poly(propylene glycol) diacrylate having a molecular weight of 230-2000 Da, preferably 400-1600 Da 0.1 to 8% by weight, preferably 3±2% by weight, of trimethylolpropane trimethacrylate, or (g) 1 to 55% by weight, preferably 10±5% by weight, of 2-phenylethyl acrylate 3 to 65% by weight, preferably 33±5% by weight, of cyclohexyl methacrylate 15 to 90% by weight, preferably 45±5% by weight, of 2-methoxyethyl acrylate 1-15% by weight, preferably 8±5% by weight, of poly(ethylene glycol) diacrylate having a molecular weight of 200-5000 Da, preferably 200-1600 Da 0.1 to 8% by weight, preferably 4±2% by weight, of ethylene glycol dimethacrylate, or (h) 1 to 70% by weight, preferably 52±5% by weight, of tert-butyl acrylate 3 to 75% by weight, preferably 35±5% by weight, of tetrahydrofurfuryl acrylate 1-15% by weight, preferably 9±5% by weight, of poly(ethylene glycol) diacrylate having a molecular weight of 200-2000 Da, preferably 400-1000 Da 0.1 to 8% by weight, preferably 3±2% by weight, of tri(ethylene glycol) dimethacrylate, or (i) 1 to 55% by weight, preferably 17±5% by weight, of benzyl acrylate 2 to 45% by weight, preferably 25±5% by weight, of 1-adamantyl methacrylate 15 to 80% by weight of triethylene glycol methyl ether methacrylate and / or 2 to 45% by weight of 2-ethoxyethyl methacrylate, preferably 37±5% by weight of triethylene glycol methyl ether methacrylate and 17±5% by weight of 2-ethoxy Ethyl Methacrylate 1-15% by weight, preferably 3±2% by weight, of poly(ethylene glycol) diacrylate having a molecular weight of 200-5000 Da, preferably 200-1600 Da 0.1 to 8% by weight, preferably 3±2% by weight, of trimethylolpropane triacrylate, or (j) 1 to 75% by weight, preferably 22±5% by weight, of ethyl methacrylate 2 to 75% by weight of 2-methoxyethyl acrylate and / or 2 to 75% by weight of 2-ethoxyethyl methacrylate, preferably 23±5% by weight of 2-methoxyethyl acrylate and 44±5% by weight of 2-ethoxyethyl methacrylate 1-15% by weight, preferably 9±5% by weight, of poly(ethylene glycol) dimethacrylate having a molecular weight of 200-2000 Da, preferably 200-1000 Da 0.1 to 8% by weight, preferably 2±1% by weight, of tetra(ethylene glycol) dimethacrylate, or (k) 1 to 55% by weight, preferably 27±5% by weight, of 2-phenylethyl methacrylate 2 to 55% by weight, preferably 14±5% by weight, of isobornyl methacrylate 15 to 80% by weight, preferably 48±5% by weight, of 2-methoxyethyl acrylate 1-15% by weight, preferably 7±5% by weight, of poly(ethylene glycol) diacrylate having a molecular weight of 200-5000 Da, preferably 200-1600 Da 0.1 to 8% by weight, preferably 4±2% by weight, of ethylene glycol dimethacrylate, or (l) 1 to 65% by weight, preferably 27±5% by weight, of methyl methacrylate 10 to 85% by weight, preferably 65±5% by weight, of 2-(2-methoxyethoxy)ethyl methacrylate 1-15% by weight, preferably 4±2% by weight, of poly(propylene glycol) diacrylate having a molecular weight of 230-2000 Da, preferably 400-1500 Da 0.1 to 8% by weight, preferably 4±2% by weight, of tetra(ethylene glycol) diacrylate, or (m) 1 to 55% by weight, preferably 8±5% by weight, of 2-phenylethyl acrylate 2 to 45% by weight, preferably 30±5% by weight, of 1-adamantyl methacrylate 5 to 80% by weight of 2-methoxyethyl acrylate and / or 2 to 75% by weight of di(ethylene glycol) ethyl ether acrylate, preferably 16±5% by weight of 2-methoxyethyl acrylate and 35±5% by weight of di(ethylene glycol) ethyl ether acrylate, 1-15% by weight, preferably 8±5% by weight, of poly(ethylene glycol) dimethacrylate having a molecular weight of 200-5000 Da, preferably 200-1600 Da 0.1 to 8% by weight, preferably 3±2% by weight, of di(ethylene glycol) dimethacrylate.

9. An intraocular lens composition according to any one of claims 1 to 8, further comprising in the mixture a UV light filter chromophore (preferably a benzotriazole substituted methacrylate) in an amount suitable for absorbing at least 50% of light radiation having a wavelength of 350 to 400 nm and / or a blue light filter chromophore in an amount suitable for absorbing at least 50% of light radiation having a wavelength of 400 to 500 nm.

10. The intraocular lens composition according to any one of claims 1 to 9, which has a water absorption amount, measured by weight, of less than 10% by weight.

11. An intraocular lens composition according to any of claims 1 to 10 for use as a foldable implantable ophthalmic device in the treatment of cataract and refractive surgery.

12. An intraocular lens, keratoprosthesis, corneal ring, corneal implant, or corneal inlay comprising an intraocular lens composition as defined in any one of claims 1 to 10.

13. 1) preparing a mixture of monomers as defined in any one of claims 1 to 10; 2) adding a preferably radical polymerization initiator; 3) polymerizing the mixture of monomers; and 4) optionally, extracting to remove by-products and / or residual unreacted monomers; A method for preparing the intraocular lens composition according to any one of claims 1 to 10, comprising:

14. 14. The method of claim 13, wherein the polymerization is carried out in an atmosphere comprising oxygen, preferably air.

15. The method of claim 13, wherein the polymerization is carried out in an inert atmosphere.

16. 16. The method according to any of claims 13 to 15, wherein the radical polymerization initiator is a diazo initiator, preferably 2,2-azobis(2,4-dimethylvaleronitrile) and / or azobisisobutyronitrile, or the radical polymerization initiator is an organic peroxide, preferably di-t-butyl peroxide, benzoyl peroxide, or methyl ethyl ketone peroxide, or the radical polymerization initiator is a photoinitiator such as phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

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