Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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SPECIFICATION
PROCESS FOR PRODUCING CYANOPSIA-CORRECTABLE
INTRAOCULAR LENS
TECHNICAL FIELD
The present invention relates to a process for producing
a cyanopsia-correctable intraocular lens and particularly to a
process for producing an intraocular lens for correction of the
cyanopsia which arises in aphakic eye patients after operation
of cataract.
BACKGROIJND ART
In recent years, with the increase in population of old
people, patients of senile cataract have increased. In aphakic
eye patients whose crystalline lens(es) has (have) been
enucleated by operation of cataract, the correction for eyesight
is generally effected by the use of any of spectacles, contact
lenses and intraocular lenses.
In effecting the above eyesight correction by
spectacles, the lenses for correction are thick convex lenses
having an unattractive appearance, and the image formed on the
retina is larger than that in normal eyes. Accordingly,
particularly when one eye is aphakic, there arises aniseikonia,
thus making larger the fatigue of optic nerve and cranial nerves
and giving a big burden to the spectacles users.
Hence, in recent years, there have been developed
contact lenses which are superior in oxygen supply to the cornea
and which give a smaller burden to the cornea even when worn for
a long time, thus providing a very effective means for eyesight
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correction in aphakic eye patients.
Further, there have been developed intraocular lenses
which are implanted into eyes and accordingly require no
detachment, and these lenses are gaining acceptance in the
market. The intraocular lenses, as compared with the above
mentioned spectacles, etc., have many advantages and are
expected to further spread in the future.
Incidentally, many of the aphakic eye patients after
cataract operation complain of glare, a difference of color
vision, etc. In particular, cyanopsia in which objects look
bluish is known generally. Cyanopsia is a disease in which,
owing to the removal of the crystalline lens(es) originally
having an yellow to yellowish brown color, a blue light (a
complementary color to an yellow to yellowish brown color)
reaches the retina without being weakened and consequently
objects look more blue than in normal eyes. Even when
artificial intraocular lenses of conventional type have been
implanted into eyes, a blue light reaches the retina without
being weakened, in the case of eyes implanted with posterior
chamber intraocular lenses made of polymethyl methacrylate
(PMMA). Consequently there is seen reduction in distingui-
shability between blue to bluish violet colors, as compared with
the case of phakic eyes.
Hence, intraocular lenses capable of correcting
cyanopsia are desired, and U.V. absorber-containing intraocular
lenses have been commercialized in order to allow the lenses to
have a light absorption characteristic close to that originally
possessed by human crystalline lenses. However, U.V. absorbers
show a very low absorption in a visible light region and is
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unable to absorb a visible blue light, though they can absorb an
U.V. light of 400 nm or less regarded to be a harmful
wavelength; therefore, with the U.V. absorber-containing
intraocular lenses, the correction of cyanopsia is incomplete.
When a large amount of an U.V. absorber is used in an
intraocular lens in order to allow the lens to have an increased
absorption in a visible light region, other properties of lens
material are decreased or worsened in many cases, which is not
preferable.
Incidentally, a so-called prepolymer process is known as
a process for producing the U.V. absorber-containing intraocular
lens mentioned above. In this prepolymer process, a monomer
solution comprising a monomer capable of forming a transparent
lens material upon polymerization, an U.V. absorber and a
polymerization initiator is introduced into a reactor and then
heated for a given length of time at a given temperature to
obtain a prepolymer of high viscosity: thereafter, the
prepolymer is filtered through a filter, casted into a cell
constituted by, for example, two glass plates and a gasket, and
then further heated for a given length of time at a given
temperature to obtain a transparent lens material.
This prepolymer process has such advantages that the
prepolyemr casted into the cell scarcely leaks out therefrom
because o-f its high viscosity and that the shrinkage degree in
the step of obtaining a transparent lens material from the
prepolymer is small, enabling the production of a transparent
lens material having a desired shape. On the other hand, the
prepolymer process has problems such as (i) polymerization is
effected in two steps thereby making the operation complicated,
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(ii) the control of the polyemerization degree and viscosity of
the prepolymer obtained in the first polymerization step is
difficult; for example, when the polymerization degree is high
and resultantly the prepolyemr viscosity is high, the filtration
treatment of the prepolymer conducted before its casting into
the cell is difficult (the filtration treatment of the
prepolymer of high viscosity is extremely difficult particularly
when there is used, for example, a filter of 0.2 ,u in pore
diameter in order to remove not only dust but also bacteria),
and (iii~ when a crosslinking monomer is used in order to allow
the polymer obtained to have a hardness, etcA, an insoluble
polymer is formed in the step of obtaining a prepolymer and the
filtration treatment becomes difficult also in this case, and
further an insoluble polyemr is formed even in the step of
polymer production after the filtration treatment and the
polymer obtained (an intraocular lens material) becomes
non-uniform.
Hence, an object of the present invention is to provide
a process for producing a cyanopsia-correctable intraocular
lens, which lens is able to eliminate the drawbacks of
conventional intraocular lenses containing an U.V. absorber and
can effectively correct the cyanopsia arising in aphakic eye
patients after operation of cataract.
Further, another object of the present invention is to
provide a process for producing a cyanopsia-correctable
intraocular lens, which process is able to obtain smoothly
without conducting a complicated operation, an intraocular lens
capable of effectively correcting the above cyanopsia.
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DISCLOSURE OF THE INVENTION
The present inventors made investigation in order to
achieve the above objects and, as a result, found that an
intraocular lens having a light absorption characteristic close
to that of human crystalline lens and being effective for
correction of cyanopsia can be obtained by a monomer cast
polymerization process in which a monomer solution comprising a
polymerizing monomer as shown below, a particular colorant and a
polymerization initiator is casted into a mold and polymerized
in a single step. The present inventors further found that the
monomer cast polymerization process can be conducted in a simple
operation as compared with the above mentioned prepolymer
process in which polymerization is effected in two steps,
and that the intraocular lens obtained is uniform.
Therefore, the present invention resides in a process
for producing a cyanopsia-correctable intraocular lens by
monomer cast polymerization, which process is characterized by
comprising steps of casting into a mold a monomer solution
comprising at least one monomer capable of forming a transparent
lens material upon polymerization, at ~least one colorant
selected from yellow, yellowish brown and orange colorants, and
a polymerization initiator; sealing the mold; and effecting
polymerization.
According to the present invention, by further adding an
U.VO absorber to the monomer solution, there can be obtained an
intraocular lens having a light absorption characteristic closer
to that of human crystalline lens and accordingly being very
effective for correction of cyanopsia.
According to the present inven-tion, by further adding a
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crosslinking monomer to the monomer solution,-there can be
obtained an intraocular lens superior in hardness, solvent
resistance, resistance -to YAG laser beam, etc.
According to the present invention, by selecting an azo
type polymerization initiator as said polymerization initiator,
there can be obtained an in-traocular lens which reduces the
significant fading of colorant oten arising when usiny a
peroxide type polymerization initiator and accordingly is stable
chemically.
BRIEF DESCRIPTION OF DRAWINGS
Figs. 1-8 are graphs showing the light transmittance
curves of cyanopsia-correctable intraocular lenses abtained
according to the present invention.
Fig. 9 is a graph showing an example of the light
transmittance curve of human crystalline lens.
Fig. 10 is a graph showing the light transmittance curve
of an intraocular lens of Comparative Example.
BEST MODE FOR CARRYING OUT THE INVENTION
In the process of the present invention for producing a
cyanopsia-correctable intraocular lens, there is firstly
prepared a monomer solution comprising at least one monomer
capable of forming a transparent lens material upon
polymerization, at least one colorant selected from yellow,
yellowish brown and orange colorants and a polymerization
initiator.
As the monomer capable of forming a -transparent lens
material upon polymerization, there are preferably used
(meth)acrylic acid esters obtaiend from (meth)acrylic acid and
alkanols of 1-6 carbon atoms (methanol, ethanol, propanol,
butanol, heptanol, hexanol). Incidentally, the "(meth)acrylic
acid" used herein means both of acyclic acid and methacrylic
acid. A particularly preferable (meth)acrylic acid ester is
methyl methacrylate. However, the monomer used in the present
invention is not restricted to the (meth)acrylic acid esters,
and there can also be used other monomers as long as they can
form a transparent lens material upon polymerization. As these
monomers, there can be mentioned, for example, (i) vinyl
group-containing monomers such as styrene, vinyl acetate and the
like, (ii) alkyl esters of unsaturated carboxylic acids such as
itaconic acid, fumaric acid, maleic acid and the like, (iii)
unsaturated carboxylic acids such as methacrylic acid, acrylic
acid, itaconic acid, fumaric acid, maleic acid and the like,
(iv) fluorine-containing monomers such as fluoro(meth)acrylate
and the like and (v) silicone-containing monomers.
The monomers can be used alone or in two or more. When
two or more monomers are used, they may be a mixture of monomers
selected from (meth)acrylic acid esters, or a mixture of a
(meth)acrylic acid ester and other monomer as mentioned above.
The monomer solution further comprises, as an essential
component, at least one coloran-t selected from yellow, yellowish
brown and orange colorants. As the yellow colorants, although
they are not restricted to the followings, there can be
mentioned C.I. (Color Index) Solvent Yellow 16, C.I. Solvent
Yellow 29, C.I. Solvent Yellow 33, C.I. Solvent Yellow 44, C.I.
Solvent Yellow 56, C.I. Solvent Yellow 77, C.I. Solvent Yellow
93, C.I. Disperse Yellow 3, etc. Also as the yellowish brown
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coloxants, although they are not restricted to the followings,
there can be mentioned C.I. Solvent Yellow 14, C.I. Solvent
Yellow 104, C.I. Solvent Yellow 105, C.I. Solvent Yellow 110,
C.I. Solvent Yellow 112, C.I. Solvent Yellow 113, C.I. Solvent
Yellow 114, etc. Further as the orange colorants, although they
are not restricted to the followings, there can be mentioned
C.I. Solvent Orange 60, C.I. Solvent Orange 67, C.I. Solvent
Orange 68, C.I. Solvent Orange 79, C.I. Solvent Orange 80, C.I.
Solvent Orange 86, C.I. Disperse Orange 47, etc.
These colorants can be used alone or in two or more of
the same or different colors.
These colorants show the maximum absorption at a
wavelength of 320-450 nm and can absorb a visible blue light and
an U.V. light, whereby the intraocular lens obtained is endowed
an effect for correction of cyanopsia. The use of an yellow
colorant showing the maximum absorption at a wavelength of
350-400 nm is particularly preferable.
When only the colorant is used without using an U.V.
absorber as mentioned later, the amount of colorant used is
preferably 0.01-0.05% (W/V) based on total monomer amount. The
reason is that when the amount is less than 0.01% (W/V), the
resulting intraocular lens shows an insufficient absorption and,
when the amount is more than 0.05% (W/V), the resulting
intraocular lens has a light absorption characteristic different
from that of human crystalline lens.
The monomer solution furthermore comprises a
polymerization initiator as an essential component~ As the
polymerization initiator, there can be used various
polymerization initiators such as azo type polymerization
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initiators, peroxide type polymerization initiators and the
like. The use of an azo type plymerization initiator is
particularly preferable. The reason is that (i) when an azo
type polymerization initiator is used in the process of the
present invention for producing a cyanopsia-correctable
intraocular lens by monomer cast polymerization, the addition
amount can be small as compared with when a peroxide type
polymerization initiator is used (for example, 2,2'-azobis-
isobutyronitrile which is an azo type polymerization initiator
is sufficient at an amount of 0.1% by weight while benzoyl
peroxide which is a peroxide type polymerization initiator is
used in an amount of 0.4% by weight), moreover, the amount of
the decomposition product of the polymerization initiator
remaining in the polymer obtained can be made small , as a
result, a chemically stable intraocular lens can be obtained,
and (ii) while the peroxide type polymerization initiator has a
bleaching action and may cause, for example, the fading of the
colorant coexisting in the monomer solution, the azo type
polyemrization initiator seldom causes such a problem.
As specific examples of the azo type polymerization
initiator, there can be mentioned l,l'-azobis(cyclohexane-
l-carbonitrile), 2,2'-azobisisobutyronitrile, 2,2'-azobis(2,4-
dimethylvaleronitrile), 2,2'-azobis(4-methoxy-2,4-dimethyl-
valeronitrile), dimethyl 2,2'-azobisisobutyrate, etc. The
amount of azo type polymerization initiator used is preferably
0.001-1.0% (W/W~ based on total monomer amount. The reason is
that when the amount is less than 0.001% (W/W), the
polymerization is insufficient and non-uniform and, when the
amount is more than 1.0% (W/W), foaming may occur.
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The monomer solution can comprise an U.V. abosrber if
necessary. The use of the U.V. absorber in combination with the
colorant can control the absorption of a light of 300-500 nm at
a desired level. Therefore, by selecting the type and addition
concentration of colorant so that the resulting intraocular lens
can have a visible region absorption characteristic close to
that of an individual human crystalline lens and further by
supplementing the shortage of U.V. region absorption by the U.V.
absorber, the resulting intraocu]ar lens can have a light
absorption characteristic closer to that of human crystalline
lens.
When the U.V. absorber is used together with the
colorant, the amount of colorant used can be 0.01-0.03% (W/V)
based on total monomer amount and the amount of U.V. absorber
used can be 0.03-0.05% (W/V). That is, in the intraocular
lenses of prior art using an U.V. absorber alone without
colorant, no light absorption characteristic curve close to that
of human crystalline lens can be obtained even when the U.V.
absorber is used in an amount of 0.3-0.5% (W/V), but in the
intraocular lens obtained according to the present invention,
the object can be achieved even when the to-tal amount of the
colorant and the U.V. absorber is as samll as 1/5 or less of the
amount of U.V. absorber used in the intraocular lenses of prior
art.
As such an U.V. absorber, there can be mentioned, for
exmaple, the followings.
Benzotriazole type
2-(2'-Hydroxy-5'-methylphenyl)benzotriazole (for
example, Tinuvin P, manufactured by Ciba-Geigy Corp.)
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2-(2'-Hydroxy-5'-tert-butylphenyl)benzotriazole
2-(2'-Hydroxy-3',5'-di-tert-butylphenyl)benzotriazole
2-(2'-Hydroxy-3'-tert-butyl-5'-methylphenyl)-5-chloro-
benzotriazole (for example, Tinuvin 326, manufactured by
Ciba-Geigy Corp.)
2-(2'-Hydroxy-3',5'-di-tert-butylphenyl)-5-chlorobenzo-
triazole
2-(2'-Hydroxy-3',5'-di-tert-amylphenyl)benzotriazole
2-(2'-Hydroxy-4'-octoxyphenyl)benzotriazole
Salicylic acid type
Phenyl salicylate
p-tert-Butylphenyl salicylate
p-Octylphenyl salicylate
Benzophenone type
2,4-Dihydroxybenzophenone
2-Hydroxy-4-methoxybenzophenone
2-Hydroxy-4-octoxybenzophenone
2-Hydroxy-4-dodecyloxybenzophenone
2,2'-Dihydroxy-4-methoxybenzophenone
2,2'-Dihydroxy-4,4'-dimethoxybenzophenone
2-Hydroxy-4-methoxy-5-sulfobenzophenone
Cyanoacrylate type
2-Ethylhexyl-2-cyano-3,3'-diphenylacrylate
Ethyl-2-cyano-3,3'-diphenyIacrylate
The monomer solution can comprise ~urther a crosslinking
monomer if necessary. By using this crosslinking monomer, the
resulting intraocular lens can have an improved hardness and
improved solvent resistance. After the transplant of
intraocular lens, there arises secondary cataract in some cases;
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in order to prevent the progress of the secondary cataract,
there is effected a treatment by an YAG laser beam; at that
time, if the YAG laser beam is misapplied on the lens, the lens
may develop cracks which may lead to lens breakage, etc. The
intraocular lens obtained by using a crosslinking monomer,
however, has a less tendency of developing cracks in the case of
misapplica-tion of YAG laser beam; moreover, the intraocular lens
scarcely gives rise to dissolution of lens monomer after the YAG
laser beam treatment and accordingly is superior also in
chemical stability.
As specific examples of the crosslinking monomer, there
can be mentioned di- or poly(meth)acrylates of diols or polyols
(herein, "(meth)acrylates" refer to both acrylates and
methacrylates), such as ethylene glycol dimethacrylate,
triethylene glycol dimethacryla-te, trimethylolpropane
triacrylate, trimethylolpropane trimethacrylate, divinylbenzene,
vinyl acrylate, vinyl me-thacrylate, allyl acrylate, allyl
methacrylate, diallyl phthalate, diethylene glycol
bisallylcarbonate and the like. The amount of crosslinking
monomer added is preferably 0.2-10% (W/V). The reason is that
when the amount is less than 0.2% (W/V), the resulting
intraocular lens has no sufficient effects for the improvement
of hardness, solvent resistance and resistance to YAG laser beam
and, when irradiated with an YAG laser beam, gives an increased
amount of monomer dissolution and; when the amount of
crosslinking monomer added is more than 10~ (W/V), the
machinability of the resulting lens becomes lower gradually.
In the process of the present invention for producing a
cyanopsia-correctable intraocular lens, the above obtained
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monomer solution comprising a polymerizable monomer, a colorant
and a polymerization initiator as essential components and, if
necessary, an U.V. absorber and/or a crosslinking monomer is
preferably subjected to a filtration treatment by a filter and
then is casted into a mold. The reason for preferably
subjecting the monomer solution to a filtration treatment by a
filter before casting into a mold is that the treatment can
remove dust and bacteria. Unlike the case in which a prepolymer
of high viscosity is subjected to a filtration treatment in the
previously mentioned prepolymer-process, the above monomer
solution has a low viscosity and can be smoothly filtered even
by the use of, for example, a filter having micro-fine pores of
0.2 ~ in pore diameter.
As the mold into which the monomer solution is casted,
there can be mentioned test tubes made of a glass, a metal or a
plastic chemically stable to the monomer used, such as
polypropylene, polye-thylene, teflon or the like, as well as
molds having an intraocular lens shape and made of the same
materials as above.
An intraocular lens can be obtained by subjecting the
obtained polymer to lathe cut and also by melting the obtained
polymer and then subjecting the molten polymer to injection or
compression molding. Therefore, the shape and size of the mold
into which the monomer solution is casted can be selected
properly.
In the process of the present invention for producing a
cyanopsia-correctable intraocular lens, the mold into which the
monomer solution has been casted is then sealed and
polymerization is effected to obtain a polymer. Unlike the case
1 31 ~75~
of the above mentioned prepolymer process, this polymerization
is effected in a single step and the operation is simple.
The polymerization is effected by a means such as
heating, U.V. light application or the like depending upon the
kind of monomer used; however, since there are ordinarily used,
as a monomer for intraocular lens, thermal polymerization type
monomers which are polymerized by heating, thermal
polymerization is effected generally. The conditions of thermal
polymerization differ by the types of monomer and polymerization
initiator used, the amount of polymerization initiator used,
etc. but a stepwise or continuous temperature elevation method
is employed ordinarily. In the case of a stepwise temperature
elevation method, heating is effected, for example, at 30-60C
for 2-100 hours, at 70-90C for 2-20 hours and at 100-120C for
2-10 hours in this order, whereby a desired polymer is obtained.
The polymer obtained is slowly cooled to 30-60C in 2-24 hours,
then let to cool to room temperature, and taken out from the
mold.
The polymer taken out from the mold is processed into an
intraocular lens using an ordinary intraocular lens processing
technique.
The present invention is further explained below by way
of Examples.
Example 1
There were used 100 ml of methyl methacrylate (MMA) as a
monomer capable of forming a transparent lens material upon
polymerization, 0.015 g (0.015% (W/V) based on total monomer
amount) of C.I. Solvent Yellow 77 as an yellow colorant, and 0.1
14
131~7~
g (about 0.1% (W/W) based on total monomer amount) of
2,2'-azobisisobutyronitrile (AIBN~ as a polymerization
initiator. They were mixed to obtain a monomer solution.
The monomer solution was subjected to a filtration
treatment with a membrane filter (pore diameter: 0.2 ~). 20 ml
of the filtrate was casted into a Pyrex~test tube (inside
diameter: 15 mm) used as a polymerization mold. The test tube
was sealed, heated for 24 hours in a water bath of 45~C, heated
in a dryer of hot air circulation type for 5 hours at 60C, for
6 hours at 80C and for 6 hours at 110C, slowly cooled to 60C
in 6 hours, and let to cool to room temperature to obtain a bar
material consisting of polymethyl methacrylate (PMMA~.
The bar material was processed into a button-shaped
material of ~ mm~ in diameter and 3 mm in thickness. The
button-shaped material was lathe-cut and polished to obtain an
intraocular lens having a diameter of 6.5 mm ~, a center
thickness of 1.0 mm and a refraction power of principal point in
aqueous, of l20 D. The light transmittance curve of the
intraocular lens was measured by an ultraviolet-visible region
spectrophotometer, UV-240 manufactured by Shimadzu Corp. As
shown in Fig. 1, the intraoculax lens shows an absorption from
300 nm to the vicinity of 500 nm, and it became clear that the
light absorption characteristic is close to that of human
crystalline lens (an example of the light transmittance curve of
human crystalline lens is shown in Fig. 9) and is effective for
correction of cyanopsia.
Example ~
The same procedure as in Example 1 was repeated except
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that 0.03% (W/V), based on total monomer amount, of C.I. Solvent
Yellow 29 was used as an yellow colorant in place of the C.I.
Solvent Yellow 77 used in Example 1, to obtain an intraocular
lens having a diameter of 6.5 mm~ , a center thickness of 1.0 mm
and a refraction power of principal point in aqueous, of +20 D.
The intraocular lens was measured for light
transmittance curve in the same manner as in Example 1. The
result is shown in Fig. 2. As shown in Fig. 2, the intraocular
lens, similarly to the intraocular lens of Example 1, shows an
absorption from 300 nm to the vicini-ty of 500 nm, and it became
clear that the light absorption characteristic is close to that
of human crystalline lens and is effective for correction of
cyanopsia.
Example 3
There were used 100 ml of methyl methacrylate (MMA) as a
monomer capable of forming a transparent lens material upon
polymerization, 0.015 g (0.015% (W/V) based on total monomer
amount) of C.I. Yellow 77 as an yellow colorant, 0.03 g (0.03%
(W/V) based on total monomer amount) of Tinuvin P (manufactured
by Ciba-Geigy Corp.) as an U.V. absorber, and 0.1 g (about 0.1
(W/W) based on total monomer amount) of 2,2'-azobisisobutyro-
nitrile (AIBN) as a polymerization initiator. They were mixed
to obtain a monomer solution.
The monomer solution was subjected to a filtration
treatment with a membrane filter (pore diameter: 0.2 ~). 20 ml
of the filtrate was casted into a Pyrex test tube (inside
diametero 15 mm) used as a polymerization mold. The test tube
was sealed, heated for 24 hours in a water bath of 45C, heated
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in a dryer of hot air circulation type for 5 hours at 60C, for
6 hours at 80C and for 6 hours at 110C, slowly cooled to 60C
in 6 hours, and let to cool to room temperature to obtain a bar
material consisting of polymethyl methacrylate (PMMA).
The bar material was processed into a button-shaped
material of 8 mm~ in diameter and 3 mm in thickness. The
button-shaped material was la-the-cut and polished to obtain an
intraocular lens having a diameter of 6.5 mm ~, a center
thickness of 1.0 mm and a refraction power of principal point in
aqueous, of +20 D.
The light transmittance curve of the intraocular lens
was measured in the same manner as in Example 1. The result is
shown in Fig. 3. In the intraocular lens of Example 1 using
only an yellow colorant without using any ultraviolet absorber,
sliyht light transmittance was seen in an ultraviolet region
(300-370 nm), as shown in Fig. 1. In the intraocular lens of
this Example, however, complete absorption of a light in the
above ultraviolet region became possible as is clear from Fig.
3. Therefore, the intraocular lens of the present Example has a
light absorption charactexistic closer to that of human
crystalline lens and is particularly effective for correction of
cyanopsia.
As a comparative example corresponding to the prior art,
there was obtained an intraocular lens in the same procedure as
in Example 3 except that no yellow colorant was used and 0.3%
(W/V), based on total monomer amount, of Tinuvin P was used as
an U.V. absorber. The light transrnittance curve of this
comparative intraocular lens containing a large amount of an
U.V. absorber is shown in Fig. 10. As is clear from Fig. 10, in
Y~
-the comparative intraocular lens, although the lens contained a
very large amount of an U.V. absorber, it was impossible to
obtain a light transmittance curve closer to that of human
crystalline lens than in Example 3.
From these results, it became clear that the intraocular
lens of Example 3 can achieve a light absorption characteristic
closer to that of human crystalline lens than the comparative
intraocular lens, although the total amount of colorant and U.V.
absorber in the lens was very small at 3/20 of the amount of
U.V. abosrber in the comparative intraocular lens.
Examples 4-7
The intraocular lenses of Examples 4-7 were obtained in
the same procedure as in Example 3 except that there were used
the following yellow colorants and U.V. absorbers.
(Example 4)
Yellow colorant: 0.03% (W/V), based on total monomer
amount, of C.I. Solvent Yellow 29
U.V. absorber : 0.03% (W/V), based on total monomer
amount, of Tinuvin P (manufactured by
Ciba-Geigy Corp.)
(Example 5)
Yellow colorant: 0.01% (W/V), based on total monomer
amount, of C.I. Solvent Yellow 16
U.V. absorber : 0.05% (W/V), based on total monomer
amount, of Tinuvin 326 (manufactured by
Ciba-Geigy Corp.)
(Example 6)
Yellow colorant: 0.01% (W/V), based on total monomer
18
1 31 ~ ~,3~s
amount, of C.I. Solvent Yellow 93
U.V. absorber : 0.05% (W/V), based on total monomer
amount, of Tinuvin 326 (manufactured by
Ciba-Geigy Corp.)
(Example 7)
Yellow colorant: 0.01% (W/V), based on total monomr
amount, of C.I. Solvent Yellow 56
U.V. absorber : 0.05% (W/V), based on total monomer
amount, of Tinuvin 326 (manufactured by
Ciba-Geigy Corp.)
The intraocular lenses of Examples 4, 5, 6 and 7 were
measured for light transmittance curve in the same manner as in
Example 1. The results are shown in Figs. 4, 5, 6 and 7,
respectively.
It became clear that the light transmittance curves of
the intraocular lenses of Examples 4-7 shown in Figs. 4-7 are
close to the light absorption characteristic of human
crystalline lens, similarly to the case of the intraocular lens
of Example 3 and are particularly effective for correction of
cyanopsia.
Example 8
An intraocular lens was obtained by using the same
yellow colorant and U.V. absorber as in Example 6 but in amounts
different from those in Example 6. The amount of the yellow
colorant used (C.I. Solvent Yellow 93) was 0.03% (W/V) based on
total monomer amount (0.01% (W/V) in Example 6), and the amount
of the U.V. absorber (Tinuvin 326) was 0.03% (W/V) based on
total monomer amount (0.05% (W/V) in Example 6).
19
7 ~ ~
The intraocular lens was measured for light
transmittance curve and the result is shown in Fig. 8. From
Fig. 8, it became clear that the intraocular lens of the present
E~ample can absorb a visible region light of 400-500 nm in a
larger extent than the intraocular lens of Example 6 and that by
appropriately varying the addition amounts of yellow colorant
and U.V. absorber, there can be obtained various
cyanopsia-correctable intraocular lenses havin~ different li~ht
absorption characteristics. This has a very important
significance when considering that the light transmittance curve
of human crystalline lens changes with the aging.
Example 9
There were used 100 ml of methyl methacrylate (MMA) as a
monomer capable of forming a transparent lens mate~ial upon
polymerization, 2 9 (2% (W/V) based on total monomer amount) of
ethylene glycol dimethacryalte (EDMA) as a crosslinking monomer,
0.01 9 (0.01% (W/V) based on total monomer amount) of C.I.
Solvent Yellow 93 as an yellow colorant, 0.05 g (0.05% (W/V)
based on total monomer amountJ of Tinuvin~326 (manufactured by
Ciba-Geigy Corp.) as an V.V. absorber, and 0.1 y (about 0.1%
(W/W) based on total monomer amount) of 2,2'-azobisisobutyro-
nitrile (AIBN) as a polymerization initiator. They were mixed
to obtain a monomer solution.
The monomer solution was subjected to a filtration
treatrnent with a membrane filter (pore diameter: 0.2 ~), and 20
ml of the filtrate was casted into a Pyrex test tube (inside
diameter: 15 mm) used as a polymerization mold. The test tube
was sealed, heated for 24 hours in a water bath of 45C, heated
~ 3 ~ g 7 ~ ~
in a dryer of hot air circulation type for 5 hours at 60C, for
6 hours at ~0C and for 6 hours at 110C, slowly cooled to 60C
in 6 hours, and let to cool to room temperature to obtain a bar
material mainly consisting of polymethyl methacrylate ~PMMA).
The bar material was processed into a button-shaped
material of 8 mm~ in diameter and 3 mm in thickness. The
bar-shaped material was lathe-cut and polished to obtain an
intraocular lens having a diameter of 6.5 mm~ , a center
-thickness of 1.0 mm and a refraction power of principal point in
aqueous, of +20 D.
Next, the same proceudre as in the above case using 2%
(W/V) of a crosslinking monomer was repeated except that the
amount of crosslinking monomer was changed to 0.2% ~W/V), 10.0%
(W/V) and 15.0% (W/V) based on total monomer amount, to
additionally obtain three different intraocular lenses.
The total four intraocular lenses obtained were
confirmed to each have a light absorption characteristic close
to that of human crystalline lens and be effective as a
cyanopsia-correctable intraocular lens.
Further,these four intraocular lenses were tested for
harndess, solvent resistance, machinability, resistnace to
Nd:YAG laser beam, and dissolution of monomer, colorant or U.V.
absorber due to application of Nd:YAG laser beam. The results
are shown in Table 1 together with the results of the
intraocular lens containing no crosslinking monomer (the lens
corresponding to the intraocular lens of Example 1).
As is clear from Table 1, it was confirmed that the
addition of crosslinking monomer in an amount of 0.2-15% (W/V)
significantly improves hardness, solvent resistance and
13i87 ~3
resistance to ~Td:YAG laser beam and significantly reduces the
dissolution of monomer due to application of Nd:YAG laser beam,
as compared wit:h the case of no addition of crosslinking
monomer.
It also became clear that machinability is satisfactory
when the amount: of crosslinking monomer added is 10.0~ (W/V) or
less.
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The test methods of various properties shown in Table 1
are as follows.
(1) Hardness
Measured in accordance with JIS K 7202, using a test
piece consisting of a disc of 15 mm ~ in diameter and 5 mm in
thickness.
(2) Solvent resistance
0.5 g of a ground sample was placed in an Erlenmeyer
flask with stopper; 50 ml of benzene was added; the mixture was
allowed to stand for 5 days at room temperature with shaking at
given time intervals; and the condition of dissolution of the
sample was observed. The sample was rated as "good" in solvent
resistance when it was insoluble and as "poor" in solvent
resistance when it was soluble.
(3) Machinability
The surface condition after lathe cut was observed with
a mangifier of ~0 magnification to examine the extent of small
defects and lathe marks on the surface. An excellent surface
condition was expressed as ~ , a good surface condition as O ,
and a poor surface condition as ~.
(4) Resistance to Nd:YAG laser beam
A Nd:YAG laser beam having a power of 2 mJ (millijoule)
was allowed to hit the posterior surface of an intraocular lens
and then the change of the intraocular lens was observed with a
magnifier. The change of the intraocular lens after application
of Nd:YAG laser beam is rated in two items of pits and cracks.
The pits are through-holes generated in the lens and
characteristic of laser beam application. Each through-hole per
se is extremely small and accordingly hardly affects the optical
24
131~ 7 r~ ~
properties of the lens. Meanwhile, the cracks refer to not only
the generation of through-holes in the lens but also the
secondary chanye of the lens material in the neighborhood of the
through-holes. The intraocular lens having cracks retain no
optical properties required for lenses, in many cases. Further,
the cracks are serious when viewed as a physical damage of lens
and, in some cases, lead to lens breakage.
(5) Dissolution of monomer, etc. due to application of ~d:YAG
laser beam
A test piece consisting of a disc of 12 mm~ in diameter
and 1 mm in thickness was placed in a 5-ml cell for
spectrophotometer, together with 4 ml of purified water. To the
surface of the tes-t piece was applied a Nd:YAG laser beam 100
times at a power of 10 mJ (millijoule). After the application,
the test piece was taken out and the absorbance at the maximum
absorption wavelength (206 nm) of the monomer was measured by a
spectrophotometer. Using a calibration curve prepared
beforehand, there was calculated the amount of monomer ~in terms
of MMA (unit: ~g)) dissolved in water owing to the application
of the Nd:YAG laser beam.
With respect to the colorant and the U.V. absorber,
there were measured absorbances at the respective maximum
absorption wavelengths (detection limit: 0.007 ppm).
As illustrated also in Examples, according to the
present invention there has been provided a process for
producing a cyanopsia-correctable intraocular lens, which lens
is able to effectively correct the cyanopsia arising in aphakic
eye patients after operation of cataract.
According to the present invention there has also been
~3187~
provided a process for producing a cyanopsia-correctable
intraocular lens, which process is able to obtain s~oothly
without requiring a complicated operation, an intraocular lens
capable of effectively correcting the above cyanopsia.
26
