JP3429390B2 - Flexible intraocular lens - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a soft intraocular lens that can be easily inserted through a small incision, and more specifically, it can be inserted into the eye by holding the lens slightly bent and then releasing the force. The present invention relates to a soft intraocular lens having a high refractive index, which recovers to its original shape and stabilizes in an appropriate time without the optical parts sticking to each other.

[0002]

2. Description of the Related Art With the increase in the elderly population, the number of patients with senile cataract has been increasing. Treatment of cataracts is performed by removing the cloudy lens nucleus and cortex, correcting the visual acuity with glasses or contact lenses, or inserting an intraocular lens.Currently, the intraocular lens is taken after total lens removal. The method of fixing is widely practiced. As the lens material, PMMA (polymethylmethacrylate), which has excellent biocompatibility and processability, is the mainstream.

On the other hand, with the recent widespread use of ultrasonic emulsification and suction, small incision surgery has become popular for the purpose of reducing postoperative astigmatism. At present, it seems that many lenses for small incision surgery are made of silicone, which has a proven record as a coating material and a breast reconstruction material. However, it is difficult to bend and fix the silicone lens, and a special injector is required, and since the shape recovery force from the bent state is strong, it is easy to damage the cells in the capsule. In addition, there are various problems such as extremely few cell adhesions, inadequate intracapsular fixation, and relatively high postoperative inflammation and cloudiness.

In order to solve the above-mentioned drawbacks of silicone lenses, Japanese Patent Application Laid-Open No. 4-292609 discloses a flexible resin comprising a copolymer containing two or more arylalkyl (meth) acrylates and a crosslinkable monomer as monomer components. Intraocular lenses are disclosed.

Since the soft intraocular lens described in this patent publication has a high refractive index, it has an advantage that the lens thickness can be made thin. However, when the lens is bent, it sticks in the bent state and is hard to separate, so that it does not enter the eye. It has the drawback that the insertion procedure is not easy.

On the other hand, in Example 1 of US Pat. No. 5,331,073, a copolymer containing phenoxyethyl acrylate, n-hexyl acrylate and ethylene glycol dimethacrylate as a cross-linking monomer as monomer components is used. However, the intraocular lens described in Example 1 of this US patent specification returns to its original shape within a few seconds after bending, and the shape recovery is too fast. It has the drawback of being easily damaged.

The object of the present invention is to bend the lens small and hold it, insert it into the eye, and then release the held force without causing the optical parts of the lenses to stick to each other. It is to provide a soft intraocular lens that recovers its shape and stabilizes.

[0008]

DISCLOSURE OF THE INVENTION As a result of intensive studies for achieving the above-mentioned object, the present inventor has found that a copolymer prepared by polymerizing a specific monomer mixture and a soft intraocular polymer having a high refractive index The lens has the flexibility to be bent, and even when it is bent and the optical parts of the lens come into contact with each other, it does not stick, and when the held force is released, the lens recovers its original shape in a reasonable time and stabilizes. I found that

The present invention has been completed based on the above findings, and has the general formula (I)

[Chemical 5] (In the formula, X is a hydrogen atom, a C ₁ -C ₁₈ alkyl group, or a C ₁ -C
_{18 is an} alkoxy group, a halogen atom, an aromatic group, and Y is

[Chemical 6] (Wherein n is 0, 1 or 2), and at least one benzoic acid unsaturated ester monomer represented by the general formula (II)

[Chemical 7] (In the formula, R ¹ and R ² are each independently a hydrogen atom or a methyl group, and m is 0 or an integer of 1 to 4.)
And at least one kind of perfluorooctylethyloxyalkylene (meth) acrylate monomer represented by
General formula (III)

[Chemical 8] (In the formula, R ³ is a hydrogen atom or a methyl group, and R ⁴ is C
_A copolymer containing at least one alkyl (meth) acrylate monomer represented by _{4 to} C ₁₈ linear or branched alkyl group) and a crosslinkable monomer as essential monomer components. The gist is a soft intraocular lens characterized by:

The present invention will be described in detail below. The first monomer component constituting the soft intraocular lens of the present invention is a vinyl benzoate monomer represented by the above general formula (I), which is an essential monomer for obtaining a soft intraocular lens having a high refractive index. is there.

In the above general formula (I), X is a hydrogen atom, a C ₁ -C ₁₈ alkyl group, a C ₁ -C ₁₈ alkoxy group, a halogen atom or an aromatic group, and Y is

[Chemical 9] (In the formula, n represents 0, 1 or 2). X is preferably a hydrogen atom, a methyl group, a methoxy group, a chlorine atom,
Examples thereof include bromine atom, phenyl group and benzyl group. Y is preferably a single bond (when n = 0) or —CH ₂ — (n =
1).

Specific preferred examples of the monomer (I) include vinyl benzoate, vinyl p-methylbenzoate, vinyl m-methylbenzoate, vinyl o-methylbenzoate, vinyl p-chlorobenzoate and m-chloro. Vinyl benzoate, vinyl o-chlorobenzoate, vinyl p-bromobenzoate, vinyl m-bromobenzoate, vinyl o-bromobenzoate, vinyl p-methoxybenzoate, vinyl m-methoxybenzoate, o-methoxybenzoate Vinylate, p-
Examples thereof include vinyl phenylbenzoate, vinyl p-benzylbenzoate and allyl benzoate, and particularly preferred are vinyl benzoate, vinyl p-methylbenzoate and vinyl p-chlorobenzoate.

In the present invention, the monomer of general formula (I) is preferably 40 to 90% by weight, more preferably 50% by weight.
It can be added in the range of up to 70% by weight. If the amount of the monomer (I) is less than 40% by weight, it is difficult to obtain a soft intraocular lens having a high refractive index, and if it exceeds 90% by weight, the obtained lens becomes hard, which is not preferable.

The second monomer component constituting the soft intraocular lens of the present invention is perfluorooctylethyloxyalkylene (meth) acrylate represented by the above general formula (II), and the surface adhesion of the soft intraocular lens is It is an important component for reducing the property and adding a function of recovering and stabilizing the original shape in an appropriate time of about 60 seconds.

In the above general formula (II), R ¹ and R ²
Are each independently a hydrogen atom or a methyl group, and m
Is 0 or an integer of 1 to 4.

Specific preferred examples of the monomer (II) include perfluorooctylethyloxypropylene (meth) acrylate, perfluorooctylethyloxyethylene (meth) acrylate, perfluorooctylethyl-dipropylene glycol (meth) acrylate, Perfluorooctylethyl-diethylene glycol (meth) acrylate, perfluorooctylethyl-tripropylene glycol (meth) acrylate, perfluorooctylethyl-triethylene glycol (meth) acrylate, perfluorooctylethyl-tetrapropylene glycol (meth) acrylate, Perfluorooctylethyl-tetraethylene glycol (meth) acrylate may be mentioned. Pyrene (meth) acrylate are particularly preferred.

In the present invention, the monomer of the general formula (II) is preferably 1 to 20% by weight, more preferably 5-1.
It can be added in the range of 0% by weight. Monomer (II)
Is less than 1% by weight, it becomes difficult to exert sufficient effect to reduce the surface tackiness and to recover and stabilize the original shape in an appropriate time. If it exceeds 20% by weight, the softness It is not preferable because the shape recovery property of the intraocular lens is remarkably lowered and the refractive index is lowered.

The third monomer component constituting the soft intraocular lens of the present invention is an alkyl (meth) acrylate represented by the above general formula (III), which is essential for imparting flexibility to the soft intraocular lens material. Is a component of.

In the above general formula (III), R ³ is a hydrogen atom or a methyl group, preferably a hydrogen atom, and R ⁴ is a C ₄ -C ₁₈ linear or branched alkyl group. Therefore, specific examples of the monomer represented by the general formula (III) include butyl (meth) acrylate, pentyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, cyclohexyl (meth) acrylate, Heptyl (meth) acrylate, octyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, undecyl (meth) acrylate, dodecyl (meth) acrylate, tridecyl (meth) acrylate, tetradecyl (meth) acrylate, pentadecyl ( (Meth) acrylate, octadecyl Acrylate etc. are mentioned, butyl (meth) acrylate, 2-ethylhexyl (meth)
Acrylate and nonyl (meth) acrylate are particularly preferred.

The general (III) monomer is preferably 1
It can be added in the range of 0 to 50% by weight, more preferably 20 to 40% by weight, and particularly preferably 20 to 35% by weight. If it is less than 10% by weight, it becomes difficult to give sufficient flexibility to the lens, and if it exceeds 50% by weight, the refractive index is lowered, which is not preferable.

In the present invention, each of the above-mentioned monomers (I), (II) and (III) may be a single kind or a mixture of plural kinds.

The fourth monomer component constituting the soft intraocular lens of the present invention is a crosslinkable monomer, either alone or in a mixture of 2
It is used as a mixture of two or more species. The crosslinkable monomer is an essential component for preventing plastic deformation of the lens and further improving mechanical strength, and specific examples thereof include ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, and triethylene. Glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,6-hexanediol di (meth) acrylate, 1 , 9-nonyldiol di (meth) acrylate, allyl (meth) acrylate, divinylbenzene, diallyl phthalate and the like, ethylene glycol dimethacrylate, 1,9-nonyldiol diacrylate and trimethylolpropane tri Acrylate is particularly preferred.

The amount of the crosslinkable monomer used is 0. to the total amount of the monomers of the general formulas (I), (II) and (III).
1 to 10% by weight is preferable. Particularly preferably, 0.5 to
It is 5% by weight. If it is less than 0.1% by weight, the effect of introducing the crosslinkable monomer is unlikely to be exhibited, and if it exceeds 10% by weight, brittleness is caused due to an increase in the number of crosslinking points, and mechanical strength is apt to decrease, which is not preferable.

In the present invention, in addition to the above essential components, a monomer having an ultraviolet absorbing ability can be used as a constituent component of the soft intraocular lens, and the following compounds can be mentioned as typical examples.

Japanese Patent Application No. Hei 7 (1999), which is a patent application by the applicant of the present application.
-The compound represented by the following general formula (IV) described in the specification of No. 54221

[Chemical 10] (In the formula, R ⁵ is a hydrogen atom, a halogen atom, a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkoxy group);

Japanese Patent Application No. Hei 7 (1999), which is a patent application by the applicant of the present application
Compounds represented by the following general formula (V) described in Japanese Patent No. 35228

[Chemical 11] (In the formula, R ⁶ is a hydrogen atom or a halogen atom, and R ⁷
Is a hydrogen atom or a methyl group);

A compound represented by the following general formula (VI) described in JP-A-2-63463.

[Chemical 12] (In the formula, R ⁸ is a chlorine atom or a methoxy group);

Or a compound represented by the general formula (VII) described in WO94 / 24112.

[Chemical 13] (In the formula, R ⁹ is a halogen atom or a branched C ₁ -C
₆ represents an alkoxy group, R ¹⁰ is —CH ₂ CH ₂ O—, —C.
_{H (CH 3) CH 2 O} -, - CH 2 CH (CH 3) O -, -
_{CH 2 CH 2 CH 2 OCH 2} -, - CH (CH 3) CH 2 OC
H ₂ - or _{-CH 2 CH (CH 3) OCH} 2 - shows a)

The amount of the monomer having an ultraviolet absorbing ability used is preferably 0.1 to 3% by weight based on the total amount of the monomers of the general formulas (I), (II) and (III). It is particularly preferably 0.2 to 1.5% by weight. If the amount is less than 0.1% by weight, the ultraviolet ray preventing effect cannot be expected, and even if the amount exceeds 3% by weight, the ultraviolet ray preventing effect cannot be expected to be further improved.

Colorants can also be used to color the resulting soft intraocular lens material. Specific examples of preferable colorants include various disperse dyes described in JP-A-7-24052, and CI solvent yellow 93, CI solvent yellow 44, CI solvent yellow 16, CI solvent yellow 77, CI.
Desperse Yellow 3 and the like are particularly preferable. The amount of the colorant used is preferably 0.1% by weight or less based on the total amount of the monomers of the general formulas (I), (II) and (III).

Next, a method of manufacturing the soft intraocular lens of the present invention will be described. In producing the copolymer that constitutes the soft intraocular lens of the present invention, first, a polymerization initiator is added to the above-mentioned monomer mixture and sufficiently stirred to prepare a homogeneous monomer mixture, and then the usual monomer mixture is added. Polymerize by the method. The usual method is a method in which after the radical polymerization initiator is added, the temperature is raised stepwise or continuously in the temperature range of 40 to 120 ° C., or ultraviolet rays or visible rays are irradiated.

Specific examples of the radical polymerization initiator are known as general radical polymerization initiators,
Azo-based initiators such as azobisvaleronitrile and azobisisobutyronitrile (hereinafter referred to as AIBN), and organic peroxides such as bis (4-t-butylcyclohexyl) peroxydicarbonate can be used. The amount of the initiator used is 0.5 to 5% by weight based on the total amount of the monomers.
A degree is preferable.

The copolymer constituting the soft intraocular lens of the present invention can be obtained by a mold method in which the above-mentioned monomer mixture is filled in a mold having a desired intraocular lens shape to obtain a molded product,
Polymerization is carried out in a suitable mold or container to obtain a rod-shaped, block-shaped, plate-shaped copolymer, and then the copolymer is cut at a low temperature,
It can be molded into an intraocular lens shape by a polishing method.

Further, in the case of obtaining an intraocular lens, the support portion of the lens may be manufactured separately from the lens and attached to the lens later, or may be integrally molded at the same time as the lens. Examples of the material for the supporting portion include polypropylene and PMMA.

[0035]

EXAMPLES The present invention will be further described below with reference to examples, but the present invention is not limited to these examples.

Example 1 In an ampoule tube having a volume of 30 ml, 2.6 g (65% by weight) of vinyl benzoate (BAV) as a monomer (I) and perfluoroethyloxypropylene methacrylate (BRM) as a monomer (II) of 0. 2 g (5% by weight), 1.2 g of monomer (III) butyl acrylate (BA)
(30% by weight), 0.04 g of ethylene glycol dimethacrylate (EGDM), which is a crosslinkable monomer (1% by weight based on the total amount of the above-mentioned monomers (I), (II) and (III)), and a polymerization initiator. Azobisisobutyronitrile (AIBN) 0.008 g (0.
(2% by weight), and stirred sufficiently to obtain a homogeneous monomer mixture. Teflon film (thickness 1mm)
Was injected from both sides with a glass plate (thickness: 1.3 mm) and into a mold for making an intraocular lens made of polypropylene. Next, the molding die and the molding die were transferred into a pressure polymerization furnace, and polymerization was carried out at a temperature of 110 ° C. for 2 hours in a nitrogen atmosphere at a pressure of 2 kgf / cm ^{2 to} obtain a film-shaped and intraocular lens optical part-shaped copolymer. Got The obtained copolymer was immersed in 100 ml of methanol to remove unpolymerized monomers, and then sufficiently dried to obtain a test sample, and various physical properties were measured. The physical properties were measured according to the following methods.

1. Refractive index measurement Using an Atago refractometer, e-line (5
The refractive index at 46.1 nm) was measured. 2. Adhesiveness When the intraocular lens optical part-shaped copolymer was gripped with an intraocular lens insertion instrument and the force was released in a room at 36 ° C, the adhesiveness of the lens optical part was observed. [Evaluation Criteria] ◯: The optical part does not stick at all Δ: The optical part sticks and leaves after a while ×: The optical part sticks and does not separate 3. The shape-recoverable film-like copolymer (length 10 mm, width 5 mm, thickness about 1 mm) was folded in two and the time required to return to the original shape was measured (unit is seconds).

The results of physical property characteristics are shown in Table 1. From Table 1, the copolymer obtained in this example had a high refractive index of 1.55, had no tackiness, and was capable of recovering its shape in an appropriate time of 58 seconds.

Examples 2 to 8 Polymerization was carried out in the same manner as in Example 1 except that the monomer composition was changed as shown in Table 1 to obtain copolymers. Then, the unpolymerized monomer was removed by the same operation as in Example 1, and various physical properties were measured. The results are shown in Table 1. From Table 1, the copolymers obtained in Examples 2 to 8 all have a high refractive index, no tackiness, and flexibility,
The shape was recovered in about 0 seconds.

COMPARATIVE EXAMPLE 1 Phenylethyl methacrylate (PEMA) 2.176 g (54.4 wt%), butyl acrylate (BA) 1.824 g (45.6 wt%), ethylene glycol dimethacrylate ( EGD
M) 0.12 g (3 based on the total amount of PEMA and BA
0.008 g of AIBN as a polymerization initiator (0.2% by weight based on the total amount of the above monomers) was added to a monomer mixture solution containing 100% by weight) to carry out polymerization to obtain a copolymer. Then, the unpolymerized monomer was removed by the same operation as in Example 1, and various physical properties were measured. The results are shown in Table 1. The polymer obtained in this comparative example has a low refractive index of 1.48,
Further, when the intraocular lens optical part-shaped copolymer was gripped by an intraocular lens insertion instrument and the force was released in a room at 36 ° C., the lens optical parts showed adhesiveness.

Comparative Example 2 Phenylethyl methacrylate (PEMA) 1.26 g
(31.5% by weight), phenyl acrylate (PEA)
2.74 g (68.5% by weight) and 0.12 g of ethylene glycol dimethacrylate (EGDM) (PEMA
And 3% by weight based on the total amount of PEA) were used to carry out polymerization in the same manner as in Comparative Example 1 to obtain a copolymer. Then, the unpolymerized monomer was removed by the same operation as in Comparative Example 1, and various physical properties were measured. The results are shown in Table 1. The polymer obtained in this comparative example has a high refractive index of 1.55,
When the intraocular lens optical part-shaped copolymer was gripped with an intraocular lens insertion instrument and the force was released in a room at 36 ° C., the lens optical parts showed adhesiveness.

[0042]

[Table 1]

The abbreviations in Table 1 indicate the following, respectively. BAV: vinyl benzoate (monomer (I)) BRM: perfluorooctylethyloxypropylene methacrylate (monomer (II)) PEMA: phenylethyl methacrylate (non-invention) PEA: phenylethyl acrylate (non-invention) BA: butyl acrylate (Monomer (III)) EHA: 2-ethylhexyl acrylate (monomer (III)) NA: nonyl acrylate (monomer (III)) EGDM: ethylene glycol dimethacrylate (crosslinkable monomer) 1.9NA: 1,9-nonyldioldi Acrylate (crosslinkable monomer) TMPTA: trimethylolpropane triacrylate (crosslinkable monomer)

As shown in Table 1, the materials of Examples 1 to 8 each have a high refractive index of 1.53 to 1.55, no tackiness, and a proper time of 55 to 64 seconds. It can be seen that the shape is recovered.

On the other hand, the materials of Comparative Examples 1 and 2 were
It can be seen that the adhesiveness is high and the shape recovery is relatively fast at 23 seconds and 25 seconds, which is not preferable as a material for the intraocular lens.

[0046]

EFFECT OF THE INVENTION The soft intraocular lens of the present invention allows the lens optical parts to adhere to each other in a proper time without sticking even when the lens is bent and held small and inserted into the eye, and then the force is released. It recovers its shape and stabilizes. Therefore, it has the effect of being able to assimilate in the eye without damaging the cells in the capsule. Further, since it has a high refractive index, it has an advantage that the lens can be manufactured thin.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI C08F 220/18 C08F 220/18 220/24 220/24 290/06 290/06 G02C 7/04 G02C 7/04 (56) Reference Documents JP-A-4-100001 (JP, A) JP-A-1-254165 (JP, A) JP-A-1-254166 (JP, A) JP-A-4-115213 (JP, A) JP-A-7- 24052 (JP, A) JP 4-268314 (JP, A) JP 1-299560 (JP, A) JP 1-299559 (JP, A) JP 3-228014 (JP, A) JP-A-8-224295 (JP, A) JP-A-60-1212 (JP, A) JP-A-58-24101 (JP, A) JP-A-7-33830 (JP, A) International Publication 89/007952 ( WO, A1) (58) Fields investigated (Int.Cl. ⁷ , DB name) A61L 27/00 C08F 2/44 C08F 218/02 C08F 218/10 C08F 218/12 C08F 220 / 18 C08F 220/24 C08F 290/06 G02C 7/04

Claims (10)

(57) [Claims] 1. A compound represented by the general formula (I): (In the formula, X is a hydrogen atom, a C ₁ -C ₁₈ alkyl group, or a C ₁ -C
_{18 is an} alkoxy group, a halogen atom, or an aromatic group, and Y is (Wherein n represents 0, 1 or 2) and at least one benzoic acid unsaturated ester monomer represented by the general formula (II) (In the formula, R ¹ and R ² are each independently a hydrogen atom or a methyl group, and m is 0 or an integer of 1 to 4.)
And at least one kind of perfluorooctylethyloxyalkylene (meth) acrylate monomer represented by the following general formula (III): (In the formula, R ³ is a hydrogen atom or a methyl group, and R ⁴ is C
_A copolymer containing at least one alkyl (meth) acrylate monomer represented by ( _{4 to} C ₁₈ linear or branched alkyl group) and a crosslinkable monomer as essential monomer components. A soft intraocular lens characterized by. 2. The soft intraocular lens according to claim 1, wherein the monomer of the general formula (I) is selected from the group consisting of vinyl benzoate, vinyl p-methylbenzoate and vinyl p-chlorobenzoate. 3. The soft intraocular lens according to claim 1, wherein the monomer of the general formula (II) is perfluorooctylethyloxypropylene (meth) acrylate. 4. The soft intraocular lens according to claim 1, wherein the monomer of the general formula (III) is selected from the group consisting of butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate and nonyl (meth) acrylate. 5. The soft intraocular lens according to claim 1, wherein the crosslinkable monomer is selected from the group consisting of ethylene glycol dimethacrylate, 1,9-nonyldiol diacrylate and trimethylolpropane triacrylate. 6. A crosslinkable composition comprising 40 to 90% by weight of a monomer of general formula (I), 1 to 20% by weight of a monomer of general formula (II) and 10 to 50% by weight of a monomer of general formula (III). The soft intraocular lens according to claim 1, comprising 0.1 to 10% by weight of the monomer based on the total amount of the monomers of the general formulas (I), (II) and (III). 7. The soft intraocular lens according to claim 1, which contains a monomer having an ultraviolet absorbing ability as a monomer component. 8. The intraocular soft eye according to claim 7, which contains 0.1 to 3% by weight of a monomer having an ultraviolet absorbing ability with respect to the total amount of the monomers of the general formulas (I), (II) and (III). lens. 9. The soft intraocular lens according to claim 7, which contains at least one selected from the group consisting of yellow, yellow-brown and orange colorants. 10. At least one selected from the group consisting of yellow, tan and orange colorants is represented by the general formula (I) or (I
The soft intraocular lens according to claim 9, comprising 0.1% by weight or less based on the total amount of the monomers I) and (III).