STABLE POLYMERIZABLE UV-ABSORBING COLORANT
FOR INTRAOCULAR LENS
TECHNICAL FIELD
[0001] The present invention relates to a colorant for
intraocular lenses. In particular, the present invention
relates to a polymerizable colorant having an ability to
absorb the ultraviolet light (UV) and the light in the blue
region.
BACKGROUND ART
[0002] Cataract is a disease in which the opacity and
the pigmentation arise in the crystalline lens to thereby
cause a state that the entire visual field is fogged. As
for the treatment method therefor, a surgical operation is
generally performed such that the clouded crystalline lens
is removed and an intraocular lens (IOL) is inserted into
and installed in the capsule of crystalline lens. Most of
the materials for the intraocular lens, which are used for
the treatment, are based on acrylic or silicon polymer. In
particular, for example, polymethyl methacrylate (PMMA) has
been hitherto used.
However, the intrinsic crystalline lens has a property
that the ultraviolet light is not transmitted therethrough.
On the contrary, the ultraviolet light is transmitted
1
through the conventional polymer for the intraocular lens.
Therefore, there is a risk that the retina may be damaged.
Further, the intrinsic crystalline lens is slightly
yellowish, which has a property that a part of the light in
the blue region is suppressed from being transmitted.
However, the light in the blue region is approximately
completely transmitted through the conventional transparent
polymer for the intraocular lens. Therefore, the patients
complain the glare in many cases after the operation for
inserting the intraocular lenses. Further, there has been
also a risk that any disease originating from the retina
including, for example, macular degeneration may be caused
when the light in the blue region, which has the short
wavelength and the high energy, arrives at the interior of
the eye.
In view of the above, the material for the intraocular
lens is required to have the ability to absorb the
ultraviolet light and the coloring brought about by a
yellow-based colorant. In recent years, in view of the
safety, an UV absorber monomer and/or a yellow-based
colorant monomer is/are copolymerized in many polymers for
the intraocular lens. Various monomer compounds as
described above have been hitherto developed (Patent
Documents 1 to 4 ) . Monomer compounds, which are
copolymerizable with other monomers for the intraocular
lens material, have been also developed, each of which has
a chromophore such as an azo group or the like and a UV-
2
absorbing portion such as a benzophenone skeleton or the
like in one molecule (Patent Documents 5 and 6 ) .
PRIOR ART DOCUMENTS
Patent Documents:
[0003]
Patent Document 1: JP2685980B2;
Patent Document 2: JPH10-251537A;
Patent Document 3: JPH07-028911B2;
Patent Document 4: JP2604799B2;
Patent Document 5: JPH02-232056A;
Patent Document 6: JP2006-291006A.
SUMMARY OF THE INVENTION
Problems to Be Solved by the Invention:
[0004] The polymerizable UV-absorbing colorant monomers
described in Patent Documents 5 and 6 involve the following
problem. That is, the monomers are deficient in the
stability against the pH change, especially in the
stability under alkaline conditions, and the colorant
moiety (chromophore and UV-absorbing portion) is easily
eliminated from the polymer. In particular, in the case of
the intraocular lens material which is to be implanted in
the eye for a long period of time, the risk of the
elimination of the colorant moiety is further increased.
3
In view of the above, an object of the present invention is
to obtain a polymerizable UV-absorbing colorant monomer
which is stable even under alkaline conditions.
Means for solving the Problems:
[0005] The present inventors have made diligent
investigations in order to solve the problem as described
above. As a result, it has been found out that the problem
of the stability against the pH change is caused by the
presence of any ester bond between a colorant moiety and a
polymerizable group in a monomer. Further, it has been
found out that a polymerizable UV-absorbing colorant
monomer compound represented by the following general
formula (1) can solve the problem as described above.
That is, the present invention is as follows.
One aspect of the present invention resides in a
compound represented by the following general formula (1)
(hereinafter referred to as "colorant compound of the
present invention" as well).
4
[0006]
(In the general formula (1), R1 is a hydrogen atom, a
hydroxy group, a carboxy group, an alkyl group having 1 to
8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms,
a sulfonic acid group, or a benzyloxy group, and preferably
a hydrogen atom, a methyl group, or an ethyl group. R2 is
a hydrogen atom, a hydroxy group, or an alkoxy group having
1 to 4 carbon atoms, and preferably a hydrogen atom, a
hydroxy group, a methoxy group, or an ethoxy group. R3 is
represented by the following formula (2).)
[0007]
(In the general formula (2), R4 is a hydrogen atom or a
methyl group. Further, R5 is a single bond or an alkylene
group having 1 to 4 carbon atoms which may have a
substituent or substituents, preferably an alkylene group
having 1 to 4 carbon atoms which has no substituent.)
[0008] Another aspect of the present invention resides
in a polymer (hereinafter referred to as "polymer of the
present invention" as well) comprising the colorant
5
compound of the present invention described above and one
species or two or more species of other polymerizable
monomers which are copolymerized with each other.
[0009] Still another aspect of the present invention
resides in an intraocular lens (hereinafter referred to as
"intraocular lens of the present invention" as well)
comprising the polymer of the present invention described
above which is molded.
EFFECT OF THE INVENTION
[0010] According to the present invention, the
polymerizable UV-absorbing colorant monomer, which is
stable even under alkaline conditions, is provided. The
compound, which is represented by the general formula (1),
has, in its molecule, the benzophenone skeleton which has
the capability to absorb the ultraviolet light, the
azobenzene skeleton which has the capability to absorb the
light in the blue region, and the polymerizable group.
Therefore, the compound represented by the general formula
(1) can be copolymerized with another polymerizable monomer
or polymerizable monomers to obtain a polymer. The polymer
is useful as a material for the intraocular lens.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011]
Fig. 1 shows a chart illustrating a UV-visible
6
absorption spectrum of a polymer sheet obtained in Example
13.
Fig. 2 shows a chart illustrating a UV-visible
absorption spectrum of a polymer sheet obtained in Example
14.
Fig. 3 shows a chart illustrating UV-visible
absorption spectrums of filtrates obtained after alkalitreating
polymers.
MODE FOR CARRYING OUT THE INVENTION
[0012] The present invention will be explained in detail
below.
[0013] <1> Colorant compound of the present invention
The colorant compound of the present invention is
represented by the following general formula (1).
[0014]
[0015] In the general formula (1), R1 is a hydrogen
atom, a hydroxy group, a carboxy group, an alkyl group
having 1 to 8 carbon atoms, an alkoxy group having 1 to 8
carbon atoms, a sulfonic acid group, or a benzyloxy group.
Among them, it is preferable to use the hydrogen atom, a
7
methyl group, or an ethyl group in view of the reaction
efficiency in the production. In the general formula (1),
R2 is a hydrogen atom, a hydroxy group, or an alkoxy group
having 1 to 4 carbon atoms. Among them, it is preferable
to use the hydrogen atom, the hydroxy group, a methoxy
group, or an ethoxy group in view of the reaction
efficiency in the production, and it is especially
preferable to use the hydroxy group in view of the light
beam absorption characteristic. As shown in the general
formula (1), the colorant compound of the present invention
has the benzophenone skeleton and the azobenzene skeleton,
and they are the colorant moieties. In the general formula
(1), R3 is represented by the following formula (2).
[0016]
[0017] In the general formula (2), R4 is a hydrogen atom
or a methyl group.
In the general formula (2), R5 is a single bond or an
alkylene group having 1 to 4 carbon atoms which may have a
substituent or substituents, preferably an alkylene group
having 1 to 4 carbon atoms which has no substituent. The
alkylene group having 1 to 4 carbon atoms specifically
means a methylene group, an ethylene group, a propylene
group, or a butylene group. The alkylene group as
8
described above may have a substituent or substituents, or
the alkylene group as described above may have no
substituent. When the alkylene group as described above
has a substituent or substituents, it is possible to
exemplify such a mode that a substituent or substituents
including, for example, an alkyl group having 1 to 2 carbon
atoms, a halogen group, a carboxyl group, a carboxy-C1 to
C2-alkyl group, a hydroxy group, a hydroxyalkyl group
having 1 to 2 carbon atoms, an amino group, and an
aminoalkyl group having 1 to 2 carbon atoms is/are bonded
to a carbon atom or atoms of the alkylene group.
As described above, the substituent R3 is the group in
which the spacer is bonded to the (meth)acryloylamino group
which is the polymerizable group, and the substituent R3 is
the moiety which participates in the copolymerization in
the colorant compound of the present invention. Owing to
the structure represented by the general formula (2), the
colorant compound of the present invention has a property
that the reaction efficiency is high with respect to other
polymerizable monomers.
The term "(meth)acryloyl" means "acryloyl" or
"methacryloyl".
In the general formula (1), it is preferable that the
substituent R3 is bonded to the 3-position or the 4-
position of the azophenyl group.
[0018] The colorant compound of the present invention
represented by the general formula (1) is not particularly
9
limited, for example, those having the following structure
may be preferably exemplified.
[0019]
[0020]
10
[0021]
[0022]
[0023]
[0024]
11
[0025]
[0026]
[0027]
[0028]
12
[0029]
[0030]
[0031]
[0032]
13
[0033]
[0034]
[0035] The colorant compound of the present invention
has, in one molecule, the benzophenone skeleton (UVabsorbing
portion) which has the capability to absorb the
ultraviolet light and the azobenzene skeleton (chromophore)
which has the capability to absorb the light in the blue
region. Owing to the presence of the colorant moiety of
them, the colorant compound of the present invention has
the capability (light beam absorption characteristic) to
suppress the transmission of those in the UV region
(wavelength: not more than 380 nm) and the blue region
(wavelength: 380 to 500 nm). The colorant compound of the
present invention is more excellent in the light beam
absorption characteristic as compared with any conventional
colorant compound (for example, 2,4-dihydroxy-5-(4-(2-(N-2-
methacryloyloxyethyl)carbamoyloxy)
14
ethylphenylazo)benzophenone (BMAC) described in Patent
Document 6. Specifically, when the UV-visible absorption
spectrum is measured, the rising of the chart sharply
appears in the vicinity of 420 to 500 nm, and the compound
is excellent in the ability to suppress the light beam
transmission in the UV/blue region.
Further, as for the colorant compound of the present
invention, the UV-absorbing portion and the chromophore
(collectively referred to as "colorant moiety" as well)
exist in one molecule. Therefore, the inconvenience, in
which the chromophore is damaged by the ultraviolet light
and the colorant is subjected to the discoloration in a
time-dependent manner, is scarcely caused.
Additionally, the polymerizable group and the colorant
moiety are connected by the amide bond in the colorant
compound of the present invention. The bond as described
above is stable even under the alkaline conditions, and
hence the colorant moiety is not eliminated from the
polymer of the present invention as described later on. As
a result, the stability under the alkaline conditions is
realized, which has been deficient in any conventional
colorant compound having the ester bond and any copolymer
based on the use of the same.
[0036] The method for producing the colorant compound of
the present invention is not specifically limited.
However, for example, the colorant compound of the present
invention can be produced in accordance with Synthesis
15
Methods 1 to 3 described below.
[0037] (Synthesis Method 1)
This method includes a diazotization step of an
aminoaryl compound to obtain a diazonium salt, a diazo
coupling step of the obtained diazonium salt and a
benzophenone compound to give a diazo compound, and an
amidation step of reacting the resulting diazo compound,
for example, with an acrylic acid compound or a methacrylic
acid compound by means of an amidation reaction to
introduce a polymerizable group.
The outline of Synthesis Method 1 is shown in the
following reaction formula. In the formula, R represents a
protecting group, R' represents a hydroxy group or a
halogen atom, and R1 to R5 represent the same or equivalent
substituents as those described above.
[0038]
[0039] (Synthesis Method 2)
This method includes an amidation step of an aminoaryl
compound, for example, with an acrylic acid compound or a
methacrylic acid compound by means of an amidation reaction
16
to introduce a polymerizable group, a diazotization step of
the obtained polymerizable aminoaryl compound to give a
diazonium salt, and a diazo coupling step of performing
diazo coupling of the resulting diazonium salt with a
benzophenone compound to give the colorant compound of the
present invention.
The outline of Synthesis Method 2 is shown in the
following reaction formula. In the formula, R represents a
protecting group, R' represents a hydroxy group or a
halogen atom, and R1 to R5 represent the same or equivalent
substituents as those described above.
In the amidation step of introducing the polymerizable
group into the aminoaryl compound, it is preferable that
the amino group on the aromatic group is blocked by the
protecting group is used, and the protecting group is
removed, for example, by means of an acid treatment before
the diazotization step.
[0040]
[0041] (Synthesis Method 3)
This method includes an amidation step of using a
17
nitroaryl compound as a starting material in place of the
aminoaryl compound and reacting it, for example, with an
acrylic acid compound or a methacrylic acid compound by
means of an amidation reaction to introduce a polymerizable
group, a reducing step of a nitro group of the obtained
polymerizable nitroaryl compound to an amino group, a
diazotization step of the obtained polymerizable aminoaryl
compound to give a diazonium salt, and a diazo coupling
step of the resulting diazonium salt with a benzophenone
compound to give the colorant compound of the present
invention.
The outline of Synthesis Method 3 is shown in the
following reaction formula. In the formula, R' represents
a hydroxy group or a halogen atom, and R1 to R5 represent
the same or equivalent substituents as those described
above.
[0042]
[0043] Alternatively, the colorant compound of the
present invention can be also produced in accordance with,
for example, a synthesis method including a protection step
18
of introducing a protecting group into an aliphatic amine
of an aminoaryl compound, a diazotization step of the
aminoaryl compound in which the aliphatic amine is
protected to obtain a diazonium salt, a diazo coupling step
of the resulting diazonium salt with a benzophenone
compound to give a diazo compound, a deprotection step of
removing the protecting group of the aliphatic amine, for
example, by means of an acid treatment, and an amidation
step of reacting the resulting diazo compound, for example,
with an acrylic acid compound or a methacrylic acid
compound by means of an amidation reaction to introduce a
polymerizable group.
[0044] The diazotization step, which is included in the
respective synthesis methods described above, can be
carried out in accordance with any known method.
It is possible to use, for example, as the diazotizing
agent, sodium nitrite or aqueous solution of sodium
nitrite, potassium nitrite or aqueous solution of potassium
nitrite, isoamyl nitrite, and/or nitrosyl sulfate (sulfuric
acid solution). The amount of use of the diazotizing agent
is not specifically limited. However, the amount of use of
the diazotizing agent is preferably 1.00 to 1.20 moles and
more preferably 1.02 to 1.10 moles per 1 mole of the
polymerizable group-containing aminoaryl compound. The
reaction temperature in the diazotization step is within a
range of -78°C to 50°C. The reaction temperature is
preferably within a range of -20°C to 20°C and more
19
preferably within a range of -20°C to 10°C. It is
preferable that the diazotization step is performed under a
neutral to acidic condition. It is possible to
appropriately add acid such as hydrochloric acid or the
like to the reaction solvent.
[0045] It is preferable that the diazo coupling step,
which is included in Synthesis Methods 2 and 3, is
performed under a weakly basic condition by using a weak
base as a catalyst, for the following reason. That is, in
the case of the strong base including, for example, sodium
hydroxide and potassium hydroxide generally used in the
diazo coupling reaction, the amide structure, which is
included in the diazonium salt of the polymerizable
aminoaryl compound, is decomposed or eliminated, and the
yield of the objective compound is lowered. On the
contrary, when the weak base is used, then the
decomposition can be remarkably suppressed, and it is
possible to secure the sufficient reactivity. As a result,
it is possible to dramatically raise the reaction yield.
Further, it is known that the vinyl group, which is
included in the diazonium salt, is also polymerized in the
presence of the strong base as described above, which
causes the conspicuous decrease in the yield. However,
when the weak base is used in place of the strong base, it
is also possible to suppress such an inconvenience.
The weak base, which is usable in this procedure, is
not specifically limited provided that the weak base is a
20
salt composed of a strong alkali and a weak acid, wherein
an aqueous solution thereof does not hydrolyze the amide
bond at 1 atm at 0°C to 25°C, causing no polymerization
reaction of the vinyl group. It is preferable to use a
weak base including, for example, sodium carbonate, sodium
hydrogencarbonate, potassium carbonate, sodium acetate, and
potassium acetate. The amount of use of the weak base is
preferably 4.0 to 10.0 moles and more preferably 6.0 to 8.0
moles per 1 mole of diazonium salt as converted into the
sodium equivalent. Further, the reaction temperature in
the diazo coupling step is within a range of -10°C to 10°C
and more preferably within a range of -5°C to 5°C.
[0046] It is possible to use, as the reaction solvent in
the diazo coupling step, organic solvents (alcohol-based
solvent such as methanol, ethanol, isopropyl alcohol and
the like, amide-based solvent such as N,Ndimethylacetoamide,
N,N-dimethylformamide, 1-methyl-2-
pyrrolidone and the like, sulfon-based solvent such as
sulforan and the like, sulfoxide-based solvent such as
dimethyl sulfoxide and the like, ureide-based solvent such
as tetramethylurea and the like, halogen-based solvent such
as dichloromethane, chloroform, 1,2-dichloroethane and the
like, ester-based solvent such as ethyl acetate, butyl
acetate and the like, ether-based solvent such as diethyl
ether, tetrahydrofuran and the like, and pyridine-based
solvent such as pyridine, a-picoline, 2,6-lutidine and the
like) singly or as a mixture system composed of a plurality
21
of types, as well as a mixture system composed of the
organic solvent and water and a system composed of water
singly. However, among them, it is preferable to use the
alcohol-based solvent. Further, it is also preferable to
use the above while mixing the same with water. Further,
it is also allowable to add and use the amide-based
solvent, the ester-based solvent, and/or the ether-based
solvent in addition to the alcohol-based solvent and the
water depending on the reaction.
[0047] The aminoaryl compound referred to herein is
represented by (i) or (v) in the reaction formula described
above, and the nitroaryl compound is represented by (ix) in
the same. Further, the polymerizable aminoaryl compound is
represented by (vi) or (vii) in the reaction formula
described above, and the polymerizable nitroaryl compound
is represented by (x) in the same.
[0048] The polymerizable aminoaryl compound or the
polymerizable nitroaryl compound described above can be
obtained, for example, by the amidation reaction of aminosubstituted
aromatic amine or nitro-substituted aromatic
amine and (meth)acrylic acid, the amidation reaction of
amino-substituted aromatic alkylamine or nitro-substituted
aromatic alkylamine and (meth)acrylic acid, the amidation
reaction of amino-substituted aromatic amine or nitrosubstituted
aromatic amine and (meth)acrylic acid chloride,
or the amidation reaction of amino-substituted aromatic
alkylamine or nitro-substituted aromatic alkylamine and
22
(meth)acrylic acid chloride. As for the amino-substituted
aromatic compound, it is possible to use those in which the
amide group is substituted with a protecting group
including, for example, t-butoxycarbonyl group,
benzyloxycarbonyl group, 9-fluorenylmethyloxycarbonyl
group, 2,2,2-trichloroethoxycarbonyl group,
allyloxycarbonyl group, p-toluenesulfonyl group, and 2-
nitrobenzenesulfonyl group.
[0049] The polymerizable aminoaryl compound described
above is exemplified, for example, by N-(4-
aminophenyl)(meth)acrylamide, N-[(4-
aminophenyl)methyl](meth)acrylamide, N-[2-(4-
aminophenyl)ethyl](meth)acrylamide, N-[3-(4-
aminophenyl)propyl](meth)acrylamide, N-[4-(4-
aminophenyl)butyl](meth)acrylamide, N-[(3-
aminophenyl)methyl](meth)acrylamide, N-[2-(3-
aminophenyl)ethyl](meth)acrylamide, N-[3-(3-
aminophenyl)propyl](meth)acrylamide, and N-[4-(3-
aminophenyl)butyl](meth)acrylamide.
Further, the polymerizable nitroaryl compound
described above is exemplified, for example, by N-(4-
nitrophenyl)(meth)acrylamide, N-[(4-
nitrophenyl)methyl](meth)acrylamide, N-[2-(4-
nitrophenyl)ethyl](meth)acrylamide, N-[3-(4-
nitrophenyl)propyl](meth)acrylamide, N-[4-(4-
nitrophenyl)butyl](meth)acrylamide, N-[(3-
nitrophenyl)methyl](meth)acrylamide, N-[2-(3-
23
nitrophenyl)ethyl](meth)acrylamide, N-[3-(3-
nitrophenyl)propyl](meth)acrylamide, and N-[4-(3-
nitrophenyl)butyl](meth)acrylamide.
[0050] As for the production method for producing the
colorant compound of the present invention, it is
preferable to use the synthesis method in which the
amidation step is performed before the diazo coupling step
as in Synthesis Method 2 or Synthesis Method 3, for the
following reason. That is, in the diazotization step of
Synthesis Method 1 described above, it is feared that any
byproduct having the high reactively may be produced by the
diazotization of aromatic amine. On the contrary,
according to Synthesis Method 2 or Synthesis Method 3
described above, the diazotization step is performed after
previously introducing the polymerizable group by means of,
for example, the amidation reaction. Therefore, it is
possible to avoid the production of the byproduct as
described above. As a result, according to Synthesis
Method 2 or Synthesis Method 3, the reaction efficiency is
satisfactory, and it is possible to obtain the colorant
compound of the present invention at a high yield.
Further, the nitroaryl compound, which is used as the
starting material in Synthesis Method 3, is more
inexpensive than the aminoaryl compound. Additionally, in
the amidation reaction, a byproduct, in which two molecules
of the polymerizable groups are introduced with respect to
the amino group, is usually produced when the polymerizable
24
group is introduced. However, the byproduct, which is
produced when the nitroaryl compound is amidated, is
removed more easily than that produced, for example, when
the aminoaryl compound is amidated. Therefore, taking the
economy and the convenience of the operation into
consideration as well, Synthesis Method 3, in which the
nitroaryl compound is used as the starting material, is
especially preferred as the production method for producing
the colorant compound of the present invention. The
colorant compound of the present invention can be
industrially produced by producing the same in accordance
with Synthesis Method 2 or Synthesis Method 3. The
colorant compound of the present invention is usable as a
useful colorant or a polymerizable UV-absorbing colorant
monomer.
[0051] <2> Polymer of the present invention
The colorant compound of the present invention can be
made into a polymer by copolymerizing the colorant compound
of the present invention with one species or two or more
species of other copolymerizable monomer or monomers. In
the colorant compound of the present invention, the
chromophore and the polymerizable group are sterically
separated from each other, and hence the polymerization is
not inhibited. Therefore, the colorant compound of the
present invention can be used as a copolymerizable monomer
which has the satisfactory reactivity with respect to other
copolymerizable monomers. Other copolymerizable monomers
25
as described above are not specifically limited provided
that the monomers are ordinarily used. However, for
example, the following monomers are exemplified.
[0052] Straight-chain, branched-chain, and cyclic
alkyl(meth)acrylates including, for example, methyl
(meth)acrylate, ethyl (meth)acrylate, propyl
(meth)acrylate, isopropyl (meth)acrylate, butyl
(meth)acrylate, tert-butyl (meth)acrylate, isobutyl
(meth)acrylate, pentyl (meth)acrylate, tert-pentyl
(meth)acrylate, hexyl (meth)acrylate, heptyl
(meth)acrylate, octyl (meth)acrylate, 2-ethylhexyl
(meth)acrylate, nonyl (meth)acrylate, decyl (meth)acrylate,
dodecyl (meth)acrylate, stearyl (meth)acrylate, cyclopentyl
(meth)acrylate, cyclohexyl (meth)acrylate, and phenoxy
(meth)acrylate;
silicon-containing (meth)acrylates including, for
example, pentamethyldisiloxanylmethyl (meth)acrylate,
pentamethyldisiloxanylpropyl (meth)acrylate,
methylbis(trimethylsiloxy)silylpropyl (meth)acrylate,
tris(trimethylsiloxy)silylpropyl (meth)acrylate,
mono(methylbis(trimethylsiloxy)siloxy)bis(trimethylsiloxy)-
silylpropyl (meth)acrylate,
tris(methylbis(trimethylsiloxy)siloxy)silylpropyl
(meth)acrylate,
methylbis(trimethylsiloxy)silylpropylglyceryl
(meth)acrylate, tris(trimethylsiloxy)silylpropylglyceryl
(meth)acrylate,
26
mono(methylbis(trimethylsiloxy)siloxy)bis(trimethylsiloxy)-
silylpropylglyceryl (meth)acrylate,
trimethylsilylethyltetramethyldisiloxanylpropylglyceryl
(meth)acrylate, trimethylsilylmethyl (meth)acrylate,
trimethylsilylpropyl (meth)acrylate,
trimethylsilylpropylglyceryl (meth)acrylate,
pentamethyldisiloxanylpropylglyceryl (meth)acrylate,
methylbis(trimethylsiloxy)silylethyltetramethyldisiloxanylmethyl
(meth)acrylate,
tetramethyltriisopropylcyclotetrasiloxanylpropyl
(meth)acrylate, and
tetramethyltriisopropylcyclotetrasiloxybis(trimethylsiloxy)
silylpropyl (meth)acrylate;
fluorine-containing (meth)acrylates including, for
example, trifluoroethyl (meth)acrylate, tetrafluoropropyl
(meth)acrylate, pentafluoropropyl (meth)acrylate,
hexafluoroisopropyl (meth)acrylate, tetrafluoro-tert-pentyl
(meth)acrylate, hexafluorobutyl (meth)acrylate, hexafluorotert-
hexyl (meth)acrylate, octafluoropentyl (meth)acrylate,
2,3,4,5,5,5-hexafluoro-2,4-bis(trifluoromethyl)pentyl
(meth)acrylate, dodecafluoroheptyl (meth)acrylate, 2-
hydroxyoctafluoro-6-trifluoromethylheptyl (meth)acrylate,
2-hydroxydodecafluoro-8-trifluoromethylnonyl
(meth)acrylate, and 2-hydroxyhexadecafluoro-10-
trifluoromethylundecyl (meth)acrylate;
styrene derivatives including, for example, styrene,
pentafluorostyrene, methylstyrene, trimethylstyrene,
27
trifluoromethylstyrene, (pentamethyl-3,3-
bis(trimethylsiloxy)trisiloxanyl)styrene, (hexamethyl-3-
trimethylsiloxytrisiloxyanyl)styrene, and
dimethylaminostyren;
hydroxy group-containing (meth) acrylates including,
for example, hydroxyethyl (meth)acrylate, hydroxypropyl
(meth)acrylate, hydroxybutyl (meth)acrylate,
dihydroxypropyl (meth)acrylate, dihydroxydibutyl
(meth)acrylate, diethylene glycol mono(meth)acrylate,
triethylene glycol mono(meth)acrylate, and dipropylene
glycol mono(meth)acrylate;
(meth)acrylic acid;
vinyl lactams including, for example, Nvinylpyrrolidone,
a-methylene-N-methylpyrrolidone, Nvinylcaprolactam,
and N-(meth)acryloylpyrrolidone;
(meth)acrylamides including, for example,
(meth)acrylamide, N-methyl(meth)acrylamide, Nethyl(
meth)acrylamide, N-hydroxyethyl(meth)acrylamide, N,Ndimethyl(
meth)acrylamide, N,N-diethyl(meth)acrylamide, and
N-ethyl-N-aminoethyl(meth)acrylamide;
aminoalkyl(meth)acrylates including, for example,
aminoethyl (meth)acrylate, N-methylaminoethyl
(meth)acrylate, and N,N-dimethylaminoethyl (meth)acrylate;
alkoxy group-containing (meth)acrylates including, for
example, methoxyethyl (meth)acrylate, ethoxyethyl
(meth)acrylate, and methoxydiethylene glycol
(meth)acrylate;
28
aromatic ring-containing (meth)acrylates including,
for example, benzyl (meth)acrylate;
alkyl esters, which may be substituted with alkyl
group, fluorine-containing alkyl group or siloxanylalkyl
group, of itaconic acid, crotonic acid, maleic acid,
fumaric acid and the like;
glycidyl (meth)acrylate;
tetrahydrofurfuryl (meth)acrylate;
4-vinylpyridine;
heterocyclic N-vinyl monomers including, for example,
vinylimidazole, N-vinylpyperidone, N-vinylpiperidine, and
N-vinylsuccinimide;
N-(meth)acryloylpiperidine; and
N-(meth)acryloylmorpholine.
The term "(meth)acrylate" means "acrylate" or
"methacrylate", and this meaning also holds in the same
manner in relation to (meth)acrylic acid derivatives.
One species or two or more species of the
copolymerizable monomers described above can be selected
and polymerized to provide a macromonomer which can be used
as one of the copolymerizable monomers for producing the
polymer as well.
[0053] The polymer of the present invention can be
obtained by blending the colorant compound of the present
invention and one species or two or more species of other
copolymerizable monomers in arbitrary amounts, mixing them
uniformly or homogeneously, and then copolymerizing them.
29
The ratio, at which the colorant compound of the present
invention is blended when the polymer of the present
invention is copolymerized, is affected by the way of use
of the polymer, for example, the thickness in the case of
the intraocular lens as well. However, the ratio is
preferably 0.001 to 5 parts by weight, more preferably
0.005 to 2 parts by weight, and much more preferably 0.01
to 0.06 parts by weight with respect to 100 parts by weight
of the mixture of all of the copolymerizable monomers. If
the ratio is less than 0.001 parts by weight, it is feared
that the color development of the polymer may be
deteriorated. On the other hand, if the ratio exceeds 5
parts by weight, it is feared that the transparency may be
lowered due to the excessive denseness of the coloring of
the polymer, the physical property (for example, the
strength) of the polymer may be lowered, and/or the
colorant compound of the present invention may be easily
eluted from the polymer.
[0054] The polymer of the present invention can be
synthesized in accordance with any method ordinarily
carried out in the concerning technical field. For
example, the polymerization can be performed by uniformly
or homogeneously mixing the colorant compound of the
present invention with one species or two or more species
of other copolymerizable monomers, adding a polymerization
initiator, if necessary, and gradually performing the
heating within a temperature range of room temperature to
30
about 130°C, or radiating an electromagnetic wave
including, for example, a microwave, an ultraviolet light,
and a radiation (gamma ray). As for the polymerization, it
is possible to adopt various methods widely and generally
used by those skilled in the art including, for example,
the radical polymerization, the bulk polymerization, and
the solvent polymerization (solution polymerization). When
the heating polymerization is performed, it is also
allowable that the temperature is raised in a stepwise
manner.
The polymerization initiator described above is
exemplified, for example, by radical polymerization
initiators including, for example, azobisisobutyronitrile,
azobisdimethylvaleronitrile, 2,2'-azobis(2,4-
dimethylvaleronitrile), benzoyl peroxide, tert-butyl
hydroperoxide, cumene hydroperoxide, and benzoyl peroxide.
It is possible to use one species or two or more species of
them. It is preferable that the polymerization initiator
is used in an amount of use within a range of about 0.01 to
1 part by weight with respect to 100 parts by weight of the
mixture of all of the copolymerizable monomers. When the
polymerization is performed by using the light beam (ray)
or the like, it is preferable to further add a
photoinitiator (photopolymerization initiator) and a
sensitizer.
[0055] When the polymer of the present invention is
synthesized, it is also possible to use, in combination, a
31
known polymerizable UV absorber (ultraviolet absorber or
absorbent) (to mainly absorb the ultraviolet light portion)
and a polymerizable colorant (having no UV-absorbing
capability to mainly absorb the light in the blue region)
as well as a polymerizable UV-absorbing colorant. When the
polymerizable UV absorber, the polymerizable colorant, and
the polymerizable UV-absorbing colorant as described above
are used in combination, it is thereby possible to finely
adjust the balance between the UV-absorbing capability and
the absorbing capability to absorb the light in the blue
region of the polymer to be finally obtained. In
particular, when the polymer of the present invention is
used as a material for the intraocular lens as described
later on, the use in combination as described above is
useful in order to adjust the color tone of the intraocular
lens and/or sufficiently add the UV-absorbing ability. The
adjustment is made so that the amount of addition is
preferably not less than 0.01 parts by weight and more
preferably not less than 0.05 parts by weight with respect
to 100 parts by weight of the mixture of all of the
copolymerizable monomers. Further, in order to secure the
sufficient polymerization speed and the sufficient degree
of polymerization, the adjustment is made so that the
amount of addition is preferably not more than 5 parts by
weight and more preferably not more than 3 parts by weight
with respect to 100 parts by weight of the mixture of all
of the copolymerizable monomers.
32
[0056] As for the polymerizable UV absorber capable of
being used in combination for the purpose as described
above, it is possible to use, for example, benzophenonebased
polymerizable UV absorbers disclosed in Japanese
Patent Application Laid-open No. 2003-253248 and
benzotriazole-based polymerizable UV absorbers disclosed in
Japanese Patent No. 2685980. Specified examples are
exemplified, for example, by benzophenone-based
polymerizable UV absorbers including, for example, 2-
hydroxy-4-(meth)acryloyloxybenzophenone, 2-hydroxy-4-
(meth)acryloyloxy-5-t-butylbenzophenone, 2-hydroxy-4-
(meth)acryloyloxy-2',4'-dichlorobenzophenone, and 2-
hydroxy-4-(2'-hydroxy-3'-
(meth)acryloyloxypropoxy)benzophenone; benzotriazole-based
polymerizable UV absorbers including, for example, 2-(2'-
hydroxy-5'-(meth)acryloyloxyethylphenyl)-2H-benzotriazole,
2-(2'-hydroxy-5'-(meth)acryloyloxyethylphenyl)-5-chloro-2Hbenzotriazole,
2-(2'-hydroxy-5'-
(meth)acryloyloxypropylphenyl)-2H-benzotriazole, 2-(2'-
hydroxy-5'-(meth)acryloyloxypropyl-3'-t-butylphenyl)-5-
chloro-2H-benzotriazole, and 2-(2'-hydroxy-5'-(2"-
methacryloyloxyethoxy)-3'-t-butylphenyl)-5-methyl-2Hbenzotriazole;
salicylic acid derivative-based
polymerizable UV absorber including, for example, 2-
hydroxy-4-methacryloyloxymethylbenzoic acid phenylester;
and 2-cyano-3-phenyl-3-(3'-(meth)acryloyloxyphenyl)propenic
acid methylester. These compounds can be used singly, or
33
two or more species of these compounds can be used in
mixture.
[0057] As for the polymerizable colorant which can be
used in combination for the purpose as described above, it
is possible to use, for example, azo-based, anthraquinonebased,
nitro-based, and phthalocyanine-based polymerizable
colorants disclosed in Japanese Patent Application Laidopen
No. 10-251537. These colorants can be used singly, or
two or more species of these colorants can be used in
mixture.
Specified examples of the polymerizable azo-based
colorant are exemplified, for example, by 1-phenylazo-4-
(meth)acryloyloxynaphthalene, 1-phenylazo-2-hydroxy-3-
(meth)acryloyloxynaphthalene, 1-naphtylazo-2-hydroxy-3-
(meth)acryloyloxynaphthalene, 1-(a-anthrylazo-2-hydroxy-3-
(meth)acryloyloxynaphthalene, 1-((4'-(phenylazo)-
phenyl)azo)-2-hycrosy-3-(meth)acryloyloxynaphthalene, 1-
(2',4'-xylylazo)-2-(meth)acryloyloxynaphthalene, and 1-(otolylazo)-
2-(meth)acryloyloxynaphthalene, 2-(m-
(meth)acryloylamide-anilino)-4,6-bis(1'-(o-tolylazo)-2'-
naphthylamino)-1,3,5-triazine, 2-(m-vinylanilino)-4-(4'-
nitrophenylazo)-anilino)-6-chloro-1,3,5-triazine, 2- (1'-(otolylazo)-
2'-naphthyloxy)-4-(m-vinylanilino)-6-chloro-
1,3,5-triazine, 2-(p-vinylanilino)-4-(1'-(o-tolylazo)-2'-
naphthylamino)-6-chloro-1,3,5-triazine, N-(1'-(o-tolylazo)-
2'-naphtyhl)-3-vinylphthalic acid monoamide, N-(1'-(otolylazo)-
2'-naphtyl)-6-vinylphthalic acid monoamide, 3-
34
vinylphthalic acid-(4'-(p-sulfonylazo)-1'-naphthyl)
monoester and 6-vinylphthalic acid-(4'-(p-sulfonylazo)-1'-
naphthyl) monoester, 3-(meth)acryloylamide-4-
phenylazophenol, 3-(meth)acryloylamide-4-(8'-hydroxy-3',6'-
disulfo-1'-naphthylazo)-phenol, 3-(meth)acryloylamide-4-
(1'-phenylazo-2'-naphthylazo)-phenol, 3-
(meth)acryloylamide-4-(p-tolylazo)phenol, 2-amino-4-(m-(2'-
hydroxy-1'-naphthylazo)anilino)-6-isopropenyl-1,3,5-
triazine, 2-amino-4-(N-methyl-p-(2'-hydroxy-1'-
naphthylazo)anilino)-6-isopropenyl-1,3,5-triazine, 2-amino-
4-(m-(4'-hydroxy-1'-phenylazo)anilino)-6-isopropenyl-1,3,5-
triazine, 2-amino-4-(N-methyl-p-(4'-
hydroxyphenylazo)anilino)-6-isopropenyl-1,3,5-triazine, 2-
amino-4-(m-(3'-methyl-1'-phenyl-5'-hydroxy-4'-
pyrazolylazo)anilino)-6-isopropenyl-1,3,5-triazine, 2-
amino-4-(N-methyl-p-(3'-methyl-1'-phenyl-5'-hydroxy-4'-
pyrazolylazo)anilino)-6-isopropenyl-1,3,5-triazine, 2-
amino-4-(p-phenylazoanilino)-6-isopropenyl-1,3,5-triazine,
and 4-phenylazo-7-(meth)acryloylamide-1-naphthol.
[0058] Specified examples of the polymerizable
anthraquinone-based colorant are exemplified, for example,
by 1,5-bis((meth)acryloylamino)-9,10-anthraquinone, 1-(4'-
vinylbenzoylamide)-9,10-anthraquinone, 4-amino-1-(4'-
vinylbenzoylamide)-9,10-anthraquinone, 5-amino-1-(4'-
vinylbenzoylamide)-9,10-anthraquinone, 8-amino-1-(4'-
vinylbenzoylamide)-9,10-anthraquinone, 4-nitro-1-(4'-
vinylbenzoylamide)-9,10-anthraquinone, 4-hydroxy-1-(4'-
35
vinylbenzoylamide)-9,10-anthraquinone, 1- (3'-
vinylbenzoylamide)-9,10-anthraquinone, 1- (2' -
vinylbenzoylamide)-9,10-anthraquinone, 1- (4'-
isopropenylbenzoylamide)-9,10-anthraquinone, 1- (3'-
isopropenylbenzoylamide)-9,10-anthraquinone, 1- (2' -
isopropenylbenzoylamide)-9,10-anthraquinone, 1,4-bis(4'-
vinylbenzoylamide)-9,10-anthraquinone, 1,4-bis(4'-
isopropenylbenzoylamide)-9,10-anthraquinone, 1,5'-bis(4'-
vinylbenzoylamide)-9,10-anthraquinone, 1,5-bis(4'-
isopropenylbenzoylamide)-9,10-anthraquinone, 1-methylamino-
4-(3'-vinylbenzoylamide)-9,10-anthraquinone, 1-methylamino-
4-(4'-vinylbenzoyloxyethylamino)-9,10-anthraquinone, 1-
amino-4-(3'-vinylphenylamino)-9,10-anthraquinone-2-sulfonic
acid, 1-amino-4-(4'-vinylphenylamino)-9,10-anthraquinone-2-
sulfonic acid, 1-amino-4-(2'-vinylbenzylamino)-9,10-
anthraquinone-2-sulfonic acid, 1-amino-4-(3'-
(meth)acryloylaminophenylamino)-9,10-anthraquinone-2-
sulfonic acid, 1-amino-4-(3'-
(meth)acryloylaminobenzylamino)-9,10-anthraquinone-2-
sulfonic acid, 1-(p-ethoxycarbonylallylamino)-9,10-
anthraquinone, 1- (p-carboxyallylamino)-9,10-anthraquinone,
1,5-di-(p-carboxyallylamino)-9,10-anthraquinone, 1-(pisopropoxycarbonylallylamino)-
5-benzoylamide-9,10-
anthraquinone, 2-(3'-(meth)acryloylamide-anilino)-4-(3'-
(3"-sulfo-4"-aminoanthraquinone-1"-yl)-amino-anilino)-6-
chloro-1,3,5-triazine, 2-(3'-(meth)acryloylamide-anilino)-
4-(3'-(3"-sulfo-4"-aminoanthraquinone-1"-yl)-amino-
36
anilino)-6-hydrzino-1,3,5-triazine, 2,4-bis-((4"-
methoxyanthraquinonen-1"-yl)-amino)-6-(3'-vinylanilino)-
1,3,5-triazine, and 2-(2'-vinylphenoxy)-4-(4'-(3"-sulfo-4"-
aminoanthraquinone-1"-yl-amino)-anilino)-6-chloro-1,3,5-
triazine.
[0059] Specified examples of the polymerizable nitrobased
colorant are exemplified, for example, by onitroanilinomethyl
(meth)acrylate.
Specified examples of the polymerizable
phthalocyanine-based colorant are exemplified, for example,
by (meth)acrylolated tetraamino copper phthalocyanine and
(meth)acrylolated (dodecanoylated tetraamino copper
phthalocyanine).
[0060] Specified examples of the polymerizable UVabsorbing
colorant capable of being used in combination for
the purpose as described above are exemplified, for
example, by benzophenone-based polymerizable UV-absorbing
colorants including, for example, 2,4-dihydroxy-3-(pstyrenoazo)
benzophenone, 2,4-dihydroxy-5-(pstyrenoazo)
benzophenone, 2,4-dihydroxy-3-(p-
(meth)acryloyloxymethylphenylazo)benzophenone, 2,4-
dihydroxy-5-(p-
(meth)acryloyloxymethylphenylazo)benzophenone, 2,4-
dihydroxy-3-(p-
(meth)acryloyloxyethylphenylazo)benzophenone, 2,4-
dihydroxy-5-(p-
(meth)acryloyloxyethylphenylazo)benzophenone, 2,4-
37
dihydroxy-3-(p-
(meth)acryloyloxypropylphenylazo)benzophenone, 2,4-
dihydroxy-5-(p-
(meth)acryloyloxypropylphenylazo)benzophenone, 2,4-
dihydroxy-3-(o-
(meth)acryloyloxymethylphenylazo)benzophenone, 2,4-
dihydroxy-5-(o-
(meth)acryloyloxymethylphenylazo)benzophenone, 2,4-
dihydroxy-3-(o-
(meth)acryloyloxyethylphenylazo)benzophenone, 2,4-
dihydroxy-5-(o-
(meth)acryloyloxyethylphenylazo)benzophenone, 2,4-
dihydroxy-3-(o-
(meth)acryloyloxypropylphenylazo)benzophenone, 2,4-
dihydroxy-5-(o-
(meth)acryloyloxypropylphenylazo)benzophenone, 2,4-
dihydroxy-3-(p-(N,Ndi(
meth)acryloyloxyethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-5-(p-(N,Ndi(
meth)acryloyloxyethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-3-(o-(N,Ndi(
meth)acryloyloxyethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-5-(o-(N,Ndi(
meth)acryloylethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-3-(p-(N-ethyl-N-
(meth)acryloyloxyethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-5-(p-(N-ethyl-N-
38
(meth)acryloyloxyethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-3-(o-(N-ethyl-N-
(meth)acryloyloxyethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-5-(o-(N-ethyl-N-
(meth)acryloyloxyethylamino)phenylazo)benzophenone, 2,4-
dihydroxy-3-(p-(N-ethyl-N-
(meth)acryloylamino)phenylazo)benzophenone, 2,4-dihydroxy-
5-(p-(N-ethyl-N-(meth)acryloylamino)phenylazo)benzophenone,
2,4-dihydroxy-3-(o-(N-ethyl-N-
(meth)acryloylamino)phenylazo)benzophenone, and 2,4-
dihydroxy-5-(o-(N-ethyl-N-
(meth)acryloylamino)phenylazo)benzophenone; and benzoic
acid-based polymerizable UV-absorbing colorants including,
for example, 2-hydroxy-4-(p-styrenoazo) benzoic acid
phenylester. These compounds can be used singly, or two or
more species of these compounds can be used in mixture.
[0061] When the polymer of the present invention is
copolymerized, it is possible to form a three-dimensional
cross-linked structure in the polymer obtained by blending
a cross-linking agent and/or using, as the copolymerizable
monomer, a macromonomer having two or more polymerizable
groups in the molecule. Accordingly, it is possible to
improve the mechanical strength and the hardness of the
polymer, and/or it is possible to suppress the elution of
the monomer (including the colorant compound of the present
invention) from the polymer. Further, when the polymer of
the present invention is used as the material for the
39
intraocular lens as described later on, then it is also
possible to obtain the intraocular lens which is uniform
and transparent, which has no distortion or no strain, and
which is excellent in the optical characteristic, and/or it
is also possible to apply the durability (resistance
against chemicals, resistance against heat, and resistance
against solvents) to the intraocular lens.
When the cross-linking agent and/or the macromonomer
is/are blended, it is preferable that the cross-linking
agent and/or the macromonomer is/are used at the blending
ratio within a range of the ratio of 0.01 to 10 parts by
weight per 100 parts by weight of the mixture of all of the
copolymerizable monomers. If the ratio is less than 0.01
parts by weight, the effect is hardly obtained. On the
other hand, if the ratio exceeds 10 parts by weight, there
is a tendency that the obtained polymer becomes fragile.
The macromonomer as described above is exemplified,
for example, by butanediol di(meth)acrylate, ethylene
glycol di(meth)acrylate, diethylene glycol
di(meth)acrylate, triethylene glycol di(meth)acrylate,
propylene glycol di(meth)acrylate, dipropylene glycol
di(meth)acrylate, diallyl fumarate, allyl (meth)acrylate,
vinyl (meth)acrylate, trimethylolpropane tri(meth)acrylate,
methacryloyloxyethyl (meth)acrylate, divinylbenzene,
diallyl phthalate, diallyl adipate, triallyl diisocyanate,
a-methylene-N-vinylpyrrolidone, 4-vinylbenzyl
(meth)acrylate, 3-vinylbenzyl (meth)acrylate, 2,2-
40
bis((meth)acryloyloxyphenyl)hexafluoropropane, 2,2-
bis((meth)acryloyloxyphenyl)propane, 1,4-bis(2-
(meth)acryloyloxyhexafluoroisopropyl)benzene, 1,3-bis(2-
(meth)acryloyloxyhexafluoroisopropyl)benzene, 1,2-bis(2-
(meth)acryloyloxyhexafluoroisopropyl)benzene, 1,4-bis(2-
(meth)acryloyloxyisopropyl)benzene, 1,3-bis(2-
(meth)acryloyloxyisopropyl)benzene, and 1,2-bis(2-
(meth)acryloyloxyisopropyl)benzene.
[0062] Further, it is also possible to apply various
functionalities to the polymer of the present invention by
selecting appropriate copolymerizable monomer or monomers.
When the oxygen permeability is applied to the polymer
of the present invention, it is appropriate to select, as
the copolymerizable monomer, for example, siliconcontaining
monomers such as silicon-containing
(meth)acrylates, silicon-containing styrene derivatives and
the like, and fluorine-containing alkyl (meth)acrylates.
When the strength of the polymer is raised and/or the
hardness is regulated, it is appropriate to select, as the
copolymerizable monomer, for example, alkyl (meth)acrylates
and styrene derivatives including styrene or (meth)acrylic
acid.
When fluorine-containing monomers, which include, for
example, fluorine-containing alkyl (meth)acrylates and
fluorine-containing styrene derivatives, are selected as
the copolymerizable monomer, it is possible to apply the
function against the pollution with lipid when the polymer
41
of the present invention is used as the material for the
intraocular lens as described later on.
When the hydrophilicity is applied to the polymer of
the present invention, it is appropriate to select, as the
copolymerizable monomer, monomers having hydrophilic groups
including, for example, hydroxy(meth)acrylates,
(meth)acrylamides, aminoalkyl(meth)acrylates,
(meth)acrylate, and N-vinyllactams. It is possible to
obtain the hydrous and soft intraocular lens when the
polymer of the present invention is used as the material
for the intraocular lens as described later on.
When monomers containing aromatic rings including, for
example, styrene-based monomers and aromatic ringcontaining
(meth)acrylates are selected as the
copolymerizable monomer, the polymer of the present
invention can be used as the material for the lens having a
high refractive index.
When the copolymerizable monomer, which is usable to
apply the various functionalities to the polymer of the
present invention, is selected and blended as described
above, the adjustment is appropriately made so that the
copolymerizable monomer is preferably not less than 0.01
parts by weight and more preferably not less than 0.05
parts by weight with respect to 100 parts by weight of the
mixture of all of the copolymerizable monomers, and the
copolymerizable monomer is not more than 5 parts by weight
and more preferably not more than 3 parts by weight with
42
respect to 100 parts by weight of the mixture of all of the
copolymerizable monomers.
[0063] As described above, the colorant compound of the
present invention has the light beam absorption
characteristic in the UV region (wavelength: not more than
380 nm) and the blue region (wavelength: 380 to 500 nm).
Therefore, the polymer of the present invention can shut
off the ultraviolet light, and the polymer of the present
invention can reduce the intensity of the light in the blue
region. Specifically, it is preferable that the light beam
transmittance is decreased from a wavelength in the
vicinity of 500 nm, and the light beam transmittance is 0%
at wavelengths of not more than 400 nm. More preferably,
when the UV-visible absorption spectrum is measured, then
the rising in the chart sharply appears in the vicinity of
420 to 500 nm, and the colorant compound of the present
invention is more excellent in the light beam transmittance
suppressing ability in the UV/blue region than the
conventional colorant compound (for example, BMAC).
Further, in order not to allow the light having the
wavelength of not more than 400 nm to be transmitted, it is
preferable to use any other UV absorber. Therefore, when
the colorant compound of the present invention is used as
the material for the intraocular lens as described later
on, it is possible to suppress the harmful influence of the
light beam on the eye.
[0064] In the polymer of the present invention, the
43
colorant compound of the present invention is directly
bonded to the polymer chain by means of the
copolymerization. Therefore, the colorant compound of the
present invention is not eluted from the polymer of the
present invention. This feature can be confirmed by the
fact that no change occurs in the spectrum of the light
beam transmittance between before and after the immersion
of the polymer of the present invention for 24 hours in
ethanol at 40°C.
Further, as described above, the amide bond, which
connects the polymerizable group and the colorant moiety in
the colorant compound of the present invention, is stable
even under the alkaline conditions (for example, at pH of
not less than 12). Therefore, the colorant moiety is not
eliminated from the polymer of the present invention. As a
result, the stability under the alkaline conditions, which
has been deficient in any copolymer based on the use of the
conventional colorant compound having the ester bond, is
realized. The high light beam absorption characteristic
can be also maintained in the polymer after the alkali
treatment. This feature can be confirmed by the fact that
the light beam transmittance, which is brought about by an
immersion solution obtained after immersing the polymer of
the present invention in a 4N sodium hydroxide aqueous
solution at room temperature for 4 hours, is substantially
100%.
[0065] <3> Intraocular lens of the present invention
44
The polymer of the present invention can be used as
the material for the intraocular lens.
In general, when a colorant compound is added to the
polymer, the colorant compound raises the hardness. On the
contrary, the colorant compound of the present invention is
excellent in the softness or flexibility. Therefore, the
intraocular lens of the present invention, which is molded
by using the polymer of the present invention as the
material for the intraocular lens, can be expected to
retain the softness, and the intraocular lens of the
present invention is easily handled when the surgical
operation is performed.
Further, the polymer of the present invention exhibits
the excellent resistance against the light and the chemical
agents, the polymer of the present invention has the high
fastness property, and the colorant moiety is not eluted
from the polymer as well. Therefore, it is possible to
obtain the excellent intraocular lens which has the high
safety and which suffers neither decolorization nor
discoloration.
Other than the above, the polymer of the present
invention can be also used as materials, for example, for
glasses, sunglasses, contact lenses, and the polymer of the
present invention can be also used for paints and building
materials.
Further, the polymer of the present invention has the
chemically stable colorant moiety, and the polymer of the
45
present invention can be used without any deterioration
even outdoors and in severe environments in which it is
estimated that the temperature change and the pH change may
be intense.
[0066] When the polymer of the present invention is used
as the material for the intraocular lens, the molding can
be performed in accordance with any known method. For
example, the following technique is exemplified. That is,
the polymerization reaction is performed in an appropriate
mold or a vessel to obtain a rod-shaped, block-shaped, or
plate-shaped polymer. After that, the polymer is processed
to have a desired shape by means of the mechanical
processing including, for example, the cutting processing
and the polishing processing. Alternatively, the
polymerization reaction is performed in a mold
corresponding to a desired shape to obtain a polymer molded
product, followed by mechanically applying the finishing
processing, if necessary.
The support portion of the intraocular lens may be
manufactured distinctly from the intraocular lens, and the
support portion may be thereafter attached. Alternatively,
no problem arises even when the support portion of the
intraocular lens is molded simultaneously (integrally) with
the intraocular lens.
[0067] When the polymer of the present invention is
molded to provide the intraocular lens, it is also
allowable that the surface modification treatment is
46
applied, if necessary, in order to make the surface of the
lens hydrophilic. It is preferable to perform the plasma
treatment or the treatment based on the ultraviolet light.
It is more preferable to perform the corona discharge
treatment, the glow discharge treatment, or the UV/ozone
treatment. When the treatment is performed as described
above, any ordinary apparatus and any ordinary methods,
which have been hitherto known, can be used as the
treatment apparatus and the treatment method.
EXAMPLES
[0068]
An example, in which an aminoaryl compound was used as
a starting material, is shown below, in relation to the
exemplary synthesis of the polymerizable aminoaryl compound
used for synthesizing the colorant compound of the present
invention.
[0069]
[Synthesis Example 1] Synthesis of N-[2-[4-(tertbutoxycarbonylamino)
phenyl]ethyl]methacrylamide
47
[0071] 2-[4-(tert-Butoxycarbonyl)phenyl]ethylamine (3.54
g) and methacrylic acid (1.57 g) were dissolved in
chloroform (80 mL), to which water-soluble carbodiimide
(2.88 g) was added while being cooled with ice. The
mixture was stirred at 4°C for 1 hour, then at room
temperature overnight, and concentrated under reduced
pressure. The residue was washed with 5% potassium
hydrogensulfate, saturated sodium hydrogencarbonate, and
brine, dried with anhydrous magnesium sulfate, and
concentrated under reduced pressure. The resulting residue
was applied to silica gel column chromatography and eluted
with hexane-ethyl acetate (volume ratio: 2:1) and
subsequently with hexane-ethyl acetate (volume ratio: 1:1).
The desired compound was obtained as white needles. The
yield was 2.92 g. Spectrum data of ^-NMR (400 MHz, CDC13)
is shown for the obtained compound.
5: 1.52 (s, 9H), 1.91 (s, 3H), 2.80 (t, 2H, J = 6.8 Hz),
3.54 (q, 2H, J = 6.8 Hz), 5.28 (t, 1H, J = 1.4 Hz), 5.59
(s, 1H), 5.76 (br.s, 1H), 6.46 (br.s, 1H), 7.12 (d, 2H, J =
8.3 Hz), 7.31 (d, 2H, J = 8.3 Hz).
[0072]
[Synthesis Example 2] Synthesis of N-[2-[4-(tertbutoxycarbonylamino)
phenyl]ethyl]acrylamide
48
[0074] 2-[4-(tert-Butoxycarbonyl)phenyl]ethylamine (2.36
g) and acrylic acid (0.84 g) were reacted in the same
manner as in Synthesis Example 1, and the objective
compound was obtained as white needles. The yield was 2.02
g. Spectrum data of ^-NMR (400 MHz, CDC13) is shown for
the obtained compound.
5: 1.52 (s, 9H), 2.80 (t, 2H, J = 6.8 Hz), 3.57 (q, 2H, J =
6.8 Hz), 5.51 (br.s, 1H), 5.62 (dd, 1H, J = 10.5 Hz, 0.9
Hz), 6.01 (dd, 1H, J = 17.4 Hz, 10.5 Hz), 6.26 (dd, 1H, J =
17.4 Hz, 0.9 Hz), 6.45 (br.s, 1H), 7.12 (d, 2H, J = 8.2
Hz), 7.30 (d, 2H, J = 8.2 Hz).
[0075]
[Synthesis Example 3] Synthesis of N-[4-(tertbutoxycarbonylamino)
benzyl]methacrylamide
[0076]
[0077] 4-(tert-Butoxycarbonylamino)benzylamine (5.38 g)
and methacrylic acid (1.89 g) were reacted in the same
manner as in Synthesis Example 1, and the objective
compound was obtained as white needles. The yield was 4.15
g. Spectrum data of ^-NMR (400 MHz, CDC13) is shown for
49
the obtained compound.
5: 1.50 (s, 9H), 1.96 (s, 3H), 4.43 (d, 2H, J = 5.4 HZ),
5.32 (t, 1H, J = 0.3 Hz), 5.68 (s, 1H), 5.96 (br.s, 1H),
6.46 (br.s, 1H), 7.21 (d, 2H, J = 8.8 Hz), 7.32 (d, 2H, J =
8.8 Hz).
[0078]
An example, in which a nitroaryl compound was used as
a starting material, is shown below, in relation to the
exemplary synthesis of the polymerizable aminoaryl compound
used for synthesizing the colorant compound of the present
invention.
[0079]
[Synthesis Example 4] Synthesis of N-[2-(4-
aminophenyl)ethyl]methacrylamide
[0080]
[0081] 2-(4-Nitrophenyl)ethylamine hydrochloride (1.72
g) and sodium hydrogencarbonate (5.00 g) were dissolved in
water (25 mL), to which ethyl acetate (25 mL) was added,
followed by being stirred in an ice bath. Methacryloyl
chloride (1.79 g) was added dropwise thereto. After
stirring for 10 minutes, the organic layer was separated.
The aqueous layer was extracted with ethyl acetate, the
organic layers were combined, washed with water and brine,
50
dried over anhydrous sodium sulfate, and evaporated under
reduced pressure. The recrystallization was performed by
using a mixture solvent of hexane and ethyl acetate. N-[2-
(4-Nitrophenyl)ethyl]methacrylamide was obtained as pale
yellowish crystals. The yield was 1.25 g (63%). Spectrum
data of 1H-NMR (400 MHz, CDCl3) is shown for the obtained
compound.
5: 1.93 (s, 3H), 2.99 (t, 2H, J = 6.8 Hz), 3.60 (q, 2H, J =
6.8 Hz), 5.32 (t, 1H, J = 1.2 Hz), 5.61 (s, 1H), 5.82
(br.s, 1H), 7.37 (d, 2H, J = 8.6 Hz), 8.17 (d, 2H, J = 8.6
Hz).
Subsequently, N-[2-(4-nitrophenyl)ethyl]methacrylamide
(1.20 g) was dissolved in ethanol (15 mL) and water (5 mL).
Ammonium chloride (364 mg) and iron powder (933 mg) were
added, and the reflux was performed at 80°C for 4 hours.
Iron powder was collected by the filtration, and the
filtrate was evaporated under the reduced pressure. Water
and ethyl acetate were added to the residual oil and the
organic layer was separated. The organic layer was washed
with water and brine, dried over anhydrous sodium filfate,
and evaporated to give the desired compound as a pale red
oily substance. The yield was 1.01 g (97%). Spectrum data
of 1H-NMR (400 MHz, CDCl3) is shown for the obtained
compound.
5: 1.91 (s, 3H), 2.74 (t, 2H, J = 6.8 Hz), 3.51 (q, 2H, J =
6.8 Hz), 3.61 (br.s, 2H), 5.27 (t, 1H, J = 1.4 Hz), 5.59
(s, 1H), 5.76 (br.s, 1H), 6.64 (d, 2H, J = 8.3 Hz), 6.98
51
(d, 2H, J = 8.3 Hz).
[0082]
[Synthesis Example 5] Synthesis of N-(4-
aminobenzyl)methacrylamide
[0083]
[0084] 4-Nitrobenzylamine hydrochloride (1.51 g) and
sodium hydrogencarbonate (4.13 g) were dissolved in water
(25 mL), to which ethyl acetate (25 mL) was added, followed
by being stirred in an ice bath. Methacryloyl chloride
(1.26 g) was added dropwise thereto. After stirring for 10
minutes, the mixture was extracted with ethyl acetate.
After washing with water and brine, the organic layer was
dried over anhydrous sodium sulfate and evaporated. After
that, the recrystallization was performed by using a
mixture solvent of hexane and ethyl acetate. N-(4-
Nitrobenzyl)methacrylamide was obtained as pale yellowish
crystals. The yield was 1.05 g (60%). Spectrum data of
1H-NMR (400 MHz, CDCl3) is shown for the obtained compound.
5: 2.01 (s, 3H), 4.61 (d, 2H, J = 6.0 Hz), 5.41 (t, 1H, J =
1.0 Hz), 5.76 (t, 1H, J = 1.0 Hz), 6.29 (br.s, 1H), 7.45
(d, 2H, J = 8.8 Hz), 8.17 (d, 2H, J = 8.8 Hz).
Subsequently, N-(4-nitrobenzyl)methacrylamide (811 mg)
was dissolved in ethanol (12 mL) and water (4 mL).
Ammonium chloride (183 mg) and iron powder (573 mg) were
52
added, and the reflux was performed at 80°C for 4 hours.
Iron powder was collected by the filtration, and the
filtrate was evaporated. Water and ethyl acetate were
added to the residue and the organic layer was separated.
The organic layer was dried over anhydrous sodium sulfate
and evaporated to give a pale red oily substance. The
yield was 580 mg (89%). Spectrum data of 1H-NMR (400 MHz,
CDCl3) is shown for the obtained compound.
5: 1.97 (t, 3H, J = 1.3 Hz), 3.67 (br.s, 2H), 4,37 (d, 2H,
J = 5.6 Hz), 5.31 (t, 1H, J = 1.4 Hz), 5.68 (br.t, 1H),
5.92 (br.s, 1H), 6,65 (d, 2H, J = 8.3 Hz), 7.09 (d, 2H, J =
8.3 Hz).
[0085]
The polymerizable UV-absorbing colorant of the present
invention was synthesized by using the polymerizable
aminoaryl compound synthesized as described above.
Examples 1 to 12 are shown below in relation thereto.
[0086]
[Example 1] Synthesis of 2,4-dihydroxy-5-[4-[2-
(methacrylamide)ethyl]phenylazo]benzophenone (hereinafter
referred to with an abbreviation of "HBZ-PHM")
[0087]
53
[0088] N-[2-[4-(tert-
Butoxycarbonylamino)phenyl]ethyl]methacrylamide (609 mg)
was dissolved in ethyl acetate (2 mL), to which 4 M
hydrogen chloride in ethyl acetate (5 mL) was added. The
mixture was stirred for 40 minutes at room temperature,
followed by being concentrated under reduced pressure. The
residue was dissolved in 1 M hydrochloric acid (4 mL), to
which an aqueous solution (10 mL) of sodium nitrite (145
mg) was added dropwise while being cooled with ice,
followed by being stirred at 4°C for 40 minutes to prepare
a diazonium salt. Subsequently, 2,4-dihydroxybenzophenone
(428 mg) was dissolved in ethanol (20 mL), to which an
aqueous solution (20 mL) of sodium carbonate (423 mg) was
added. A solution containing the diazonium salt described
above was added dropwise to the mixture while being cooled
with ice. The mixture was stirred at 4°C for 1 hour, and
then at room temperature for 4 hours, while 4 M
hydrochloric acid was added dropwise to adjust pH to 6.
Water (40 mL) was added to the mixture, and the precipitate
was collected by the filtration, followed by being washed
with water. The precipitate was dissolved in chloroform
without being dried, which was dried over anhydrous
magnesium sulfate and evaporated. Methanol was added to
54
the residue and allowed to stand at 4°C overnight. After
that, the precipitated objective compound was obtained as
orange crystals. The yield was 326 mg (38%). Spectrum
data of 1H-NMR (400 MHz, CDCl3) is shown for the obtained
compound.
1H-NMR (400 MHz, CDCl3) 5: 1.93 (t, 3, J = 1.0 Hz), 2.94
(t, 2H, J = 6.8 Hz), 3.61 (q, 2H, J = 6.8 Hz), 5.31 (t, 1H,
J = 1.0 Hz), 5.61 (t, 1H, J = 1.0 Hz), 5.80 (br.t, 1H),
6.58 (s, 1H), 7.33 (d, 2H, J = 8.8 Hz), 7.56 (t, 2H, J =
7.2 Hz), 7.64 (tt, 1H, J = 7.3 Hz, 2.4 Hz), 7.73-7.76 (m,
4H), 8.23 (s, 1H), 12.89 (s, 1H), 13.94 (s, 1H).
[0089]
[Example 2] Synthesis of 2-hydroxy-5-[4-[2-
(methacrylamide)ethyl]phenylazo]benzophenone (hereinafter
referred to with an abbreviation of "NBZ-PHM")
55
[0091] In the same manner as in Example 1, N-[2-[4-
(tert-butoxycarbonylamino)phenyl]ethyl]methacrylamide (609
mg) was subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 2-hydroxybenzophenone (396 mg). The
objective compound was obtained as orange crystals. The
yield was 630 mg (76%) . Spectrum data of ^-NMR (400 MHz,
CDCI3) is shown for the obtained compound.
^-NMR (400 MHz, CDC13) 5: 1.92 (s, 3H) , 2.93 (t, 2H, J =
6.8 Hz), 3.61 (q, 2H, J = 6.8 Hz), 5.29 (t, 1H, J = 1.2
Hz), 5.61 (s, 1H), 5.79 (br.t, 1H), 7.20 (d, 1H, J = 8.8
Hz), 7.32 (d, 2H, J = 8.3 Hz), 7.57 (t, 2H, J = 7.3 Hz),
7.66 (t, 1H, J = 7.3 Hz), 7.77-7.81 (m, 4H), 8.15 (dd, 1H,
J = 9.3 Hz, 2.4 Hz), 8.26 (d, 1H, J = 2.4 Hz), 12.44 (s,
1H) .
[0092]
[Example 3] Synthesis of 2-hydroxy-5-[4-[2-
(methacrylamide)ethyl]phenylazo]-4-methoxybenzophenone
(hereinafter referred to with an abbreviation of "MBZ-PHM")
56
[0094] In the same manner as in Example 1, N-[2-[4-
(tert-butoxycarbonylamino)phenyl]ethyl]methacrylamide (609
mg) was subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 2-hydroxy-4-methtoxybenzophenone (456 mg).
The objective compound was obtained as orange crystals.
The yield was 553 mg (62%). Spectrum data of ^-NMR (400
MHz, CDCI3) is shown for the obtained compound.
^-NMR (400 MHz, CDC13) 5: 1.92 (s, 3H) , 2.92 (t, 2H, J =
6.8 Hz), 3.60 (q, 2H, J = 6.8 Hz), 4.09 (s, 3H) , 5.29 (t,
1H, J = 1.4 Hz), 5.60 (s, 1H) , 5.76 (br.t, 1H) , 6.71 (s,
1H), 7.29 (d, 2H, J = 8.8 Hz), 7.53 (t, 2H, J = 8.8 Hz),
7.61 (t, 1H, J = 7.8 Hz), 7.71 (d, 2H, J = 6.8 Hz), 7.76
(d, 2H, J = 6.8 Hz), 8.03 (s, 1H), 12.91 (s, 1H).
[0095]
[Example 4] Synthesis of 4-ethoxy-2-hydroxy-5-[4-[2-
(methacrylamide)ethyl]phenylazo]benzophenone (hereinafter
referred to with an abbreviation of "EBZ-PHM")
57
[0097] In the same manner as in Example 1, N-[2-[4-
(tert-butoxycarbonylamino)phenyl]ethyl]methacrylamide (609
mg) was subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 4-ethoxy-2-hydroxybenzophenone (485 mg). The
objective compound was obtained as orange crystals. The
yield was 652 mg (71%). Spectrum data of ^-NMR (400 MHz,
CDCI3) is shown for the obtained compound.
^-NMR (400 MHz, CDCI3) 5: 1.59 (t, 3H, J = 6.8 Hz), 1.92
(s, 3H), 2.92 (t, 2H, J = 6.8 Hz), 3.60 (q, 2H, J = 6.8
Hz), 4.33 (q, 2H, J = 6.8 Hz), 5.29 (t, 1H, J = 1.2 Hz),
5.60 (s, 1H), 5.77 (br.t, 1H), 6.68 (s, 1H), 7.30 (d, 2H, J
= 8.3 Hz), 7.53 (t, 2H, J = 7.3 Hz), 7.61 (t, 1H, J = 7.3
Hz), 7.71 (d, 2H, J = 7.3 Hz), 7.78 (d, 2H, J = 8.4 Hz),
8.03 (s, 1H), 12.90 (s, 1H).
[0098]
[Example 5] Synthesis of 5-[4-[2-
(acrylamide)ethyl]phenylazo]-2,4-dihydroxybenzophenone
(hereinafter referred to with an abbreviation of "HBZ-PHA")
58
[0100] In the same manner as in Example 1, N-[2-[4-
(tert-butoxycarbonylamino)phenyl]ethyl]acrylamide (581 mg)
was subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 2,4-dihydroxybenzophenone (428 mg). The
objective compound was obtained. The yield was 313 mg
(38%) . Spectrum data of ^-NMR (400 MHz, CDC13) is shown
for the obtained compound.
5: 2.94 (t, 2H, J = 6.8 Hz), 3.64 (q, 2H, J = 6.4 Hz), 5.56
(br.t, 1H), 5.64 (dd, 1H, J = 10.8 Hz, 1.5 Hz), 6.03 (dd,
1H, J = 17.1 Hz, 10.8 Hz), 6.28 (dd, 1H, J = 17.1 Hz, 1.5
Hz), 6.58 (s, 1H), 7.33 (d, 2H, J = 8.3 Hz), 7.54-7.59 (m,
2H), 7.65 (t, 1H, J = 78 Hz), 7.73-7.76 (m, 4H), 8.23 (s,
1H), 12.90 (s, 1H), 13.94 (s, 1H).
[0101]
[Example 6] Synthesis of 5-[4-[2-
(acrylamide)ethyl]phenylazo]-2-hydroxy-4-
methoxybenzophenone (hereinafter referred to with an
abbreviation of "MBZ-PHA")
59
[0103] In the same manner as in Example 5, N-[2-[4-
(tert-butoxycarbonylamino)phenyl]ethyl]acrylamide (581 mg)
was subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 2-hydroxy-4-methoxybenzophenone (456 mg).
The objective compound was obtained. The yield was 510 mg
(59%) . Spectrum data of ^-NMR (400 MHz, CDC13) is shown
for the obtained compound.
5: 2.92 (t, 2H, J = 6.8 Hz), 3.62 (q, 2H, J = 6.8 Hz), 4.09
(s, 3H), 5.56 (br.t, 1H), 5.63 (dd, 1H, J = 10.2 Hz, 1.5
Hz), 6.02 (dd, 1H, J = 17.1 Hz, 10.2 Hz), 6.26 (dd, 1H, J =
17.1 Hz, 1.5 Hz), 6.70 (s, 1H), 7.29 (d, 2H, J = 8.3 Hz),
7.53 (t, 2H, J = 7.3 Hz), 7.61 (t, 1H, J = 7.8 Hz), 7.70-
7.76 (m, 4H), 8.03 (s, 1H), 12.92 (s, 1H).
[0104]
[Example 7] Synthesis of 5-[4-[2-
(acrylamide)ethyl]phenylazo]-4-ethoxy-2-hydroxybenzophenone
(hereinafter referred to with an abbreviation of "EBZ-PHA")
60
[0106] In the same manner as in Example 5, N-[2-[4-
(tert-butoxycarbonylamino)phenyl]ethyl]acrylamide (581 mg)
was subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 4-ethoxy-2-hydroxybenzophenone (485 mg). The
objective compound was obtained. The yield was 583 mg
(66%) . Spectrum data of ^-NMR (400 MHz, CDC13) is shown
for the obtained compound.
5: 1.59 (t, 3H, J = 7.1 Hz), 2.93 (t, 2H, J = 6.9 Hz), 3.64
(q, 2H, J = 6.9 Hz), 4.33 (q, 2H, J = 7.1 Hz), 5.52 (br.t,
1H), 5.63 (dd, 1H, J = 10.4 Hz, 1.3 Hz), 6.02 (dd, 1H, J =
16.9 Hz, 10.4 Hz), 6.27 (dd, 1H, J = 16.9 Hz, 1.3 Hz), 6.68
(s, 1H), 7.29 (d, 2H, J = 8.5 Hz), 7.50-7.55 (m, 2H), 7.61
(t, 1H, J = 7.4 Hz), 7.69-7.72 (m, 2H), 7.96 (d, 2H, J =
8.3 Hz), 8.02 (s, 1H), 12.89 (s, 1H).
[0107]
[Example 8] Synthesis of 5-[4-[2-
(acrylamide)ethyl]phenylazo]-2-hydroxybenzophenone
(hereinafter referred to with an abbreviation of "NBZ-PHA")
61
[0109] In the same manner as in Example 5, N-[2-[4-
(tert-butoxycarbonylamino)phenyl]ethyl]acrylamide (581 mg)
was subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 2-hydroxybenzophenone (396 mg). The
objective compound was obtained. The yield was 525 mg
(66%) . Spectrum data of ^-NMR (400 MHz, CDC13) is shown
for the obtained compound.
5: 2.94 (t, 2H, J = 6.8 Hz), 3.64 (q, 2H, J = 6.8 Hz), 5.56
(br.t, 1H), 5.63 (dd, 1H, J = 10.3 Hz, 1.5 Hz), 6.02 (dd,
1H, J = 17.1 Hz, 10.3 Hz), 6.27 (dd, 1H, J = 17.1 Hz, 1.5
Hz), 7.20 (d, 1H, J = 9.3 Hz), 7.32 (d, 2H, J = 8.3 Hz),
7.57 (tt, 2H, J = 7.3 Hz, 1.5 Hz), 7.66 (t, 1H, J = 7.8
Hz), 7.77-7.81 (m, 4H), 8.15 (dd, 1H, J = 9.3 Hz, 2.4 Hz),
8.26 (d, 1H, J = 2.4 Hz), 12.45 (s, 1H).
[0110]
[Example 9] Synthesis of 2,4-dihydroxy-5-[4-[2-
(methacrylamide)ethyl]phenylazo]benzophenone (HBZ-PHM)
62
[0111]
[0112] HBZ-PHM was synthesized in accordance with the
following method different from the method of Example 1.
1 M hydrochloric acid (15 mL) was added to N-[2-[4-
aminophenyl]ethyl]methacrylamide (930 mg), to which an
aqueous solution (5 mL) of sodium nitrite (355 mg) was
added dropwise while being cooled with ice, followed by
being stirred at 4°C for 1 hour to prepare a diazonium
salt. Subsequently, 2,4-dihydroxybenzophenone (975 mg) was
dissolved in ethanol (40 mL), to which an aqueous solution
(40 mL) of sodium carbonate (970 mg) was added. The
solution containing the diazonium salt described above was
added dropwise to the mixture while being cooled with ice.
The mixture was stirred at 4°C for 1 hour, and then at room
temperature for 2 hours, to which 4 M hydrochloric acid was
added dropwise to adjust pH to 6. Water (40 mL) was added
to the mixture, and the precipitate was collected by the
filtration, followed by being washed with water. The
precipitate was dissolved in chloroform after being dried,
which was adsorbed to silica gel. The column
chromatography was performed using ethyl acetate, and
orange crystals were obtained. Methanol was added to the
63
crystals to perform the reflux, followed by being left to
stand at room temperature overnight. The precipitated
objective compound was obtained as orange crystals. The
yield was 774 mg (40%). Spectrum data of 1H-NMR (400 MHz,
CDCl3) is shown for the obtained compound.
5: 1.93 (t, 3H, J = 1.0 Hz), 2.94 (t, 2H, J = 6.8 Hz), 3.61
(q, 2H, J = 6.8 Hz), 5.31 (t, 1H, J = 1.0 Hz), 5.61 (t, 1H,
J = 1.0 Hz), 5.81 (br.t, 1H), 6.58 (s, 1H), 7.33 (d, 2H, J
= 8.5 Hz), 7.56 (t, 2H, J = 7.2 Hz), 7.64 (tt, 1H, J = 7.2
Hz, 2.4 Hz), 7.72-7.76 (m, 4H), 8.22 (s, 1H), 12.89 (s,
1H), 13.93 (s, 1H).
[0113]
[Example 10] Synthesis of 5-[4-[2-
(methacrylamide)methyl]phenylazo]-2,4-dihydroxybenzophenone
(hereinafter referred to with an abbreviation of "HBZ-BZM")
[0114]
[0115] In the same manner as in Example 1, N-[4-(tertbutoxycarbonylamino)
benzyl]methacrylamide (581 mg) was
subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 2,4-dihydroxybenzophenone (428 mg). The
objective compound was obtained. The yield was 470 mg
(57%). Spectrum data of 1H-NMR (400 MHz, CDCl3) is shown
64
for the obtained compound.
5: 1.99 (s, 3H), 4.56 (d, 2H, J = 5.9 Hz), 5.37 (s, 1H),
5.73 (s, 1H), 6.13 (br.t, 1H), 6.57 (s, 1H), 7.25 (s, 1H),
7.41 (d, 2H, J = 8.8 Hz), 7.53-7.57 (m, 2H), 7.63 (t, 1H, J
= 7.3 Hz), 7.72-7.76 (m, 4H), 8.22 (s, 1H), 12.88 (s, 1H),
13.89 (s, 1H).
[0116]
[Example 11] Synthesis of 5-[4-[2-
(methacrylamide)methyl]phenylazo]-2-hydroxy-4-
methoxybenzophenone (hereinafter referred to with an
abbreviation of "MBZ-BZM")
[0117]
[0118] In the same manner as in Example 10, N-[4-(tertbutoxycarbonylamino)
benzyl]methacrylamide (581 mg) was
subjected to the acid treatment, followed by being
converted into a diazonium salt to perform the diazo
coupling with 2-hydroxy-4-methoxybenzophenone (456 mg).
The objective compound was obtained. The yield was 511 mg
(59%). Spectrum data of 1H-NMR (400 MHz, CDCl3) is shown
for the obtained compound.
5: 2.00 (s,3H), 4.09 (s, 3H), 4.56 (d, 2H, J = 5.9 Hz),
5.37 (s, 1H), 5.73 (s, 1H), 6.10 (br.t, 1H), 6.70 (s, 1H),
7.39 (d, 2H, J = 8.8 Hz), 7.51-7.55 (m, 2H), 7.61 (t, 1H, J
65
= 7.8 H z ) , 7.69-7.72 (m, 2 H ) , 7.78 (d, 2H, J = 8.3 H z ),
8.03 (s, 1H), 12.92 (s, 1H).
[0119]
[Example 12] Synthesis of 5-[4-[2-
(methacrylamide)methyl]phenylazo]-2-hydroxy-4-
methoxybenzophenone (MBZ-BZM)
[0120]
[0121] MBZ-BZM was synthesized in accordance with the
following method different from the method of Example 11.
1 M hydrochloric acid (9 mL) was added to N-[4-
aminobenzyl]methacrylamide (574 mg), to which an aqueous
solution (3 mL) of sodium nitrite (210 mg) was added
dropwise while being cooled with ice, followed by being
stirred at 4°C for 1 hour to prepare a diazonium salt.
Subsequently, 2,4-dihydroxybenzophenone (637 mg) was
dissolved in ethanol (25 mL), to which an aqueous solution
(25 mL) of sodium carbonate (644 mg) was added. The
solution containing the diazonium salt described above was
added dropwise to the mixture while being cooled with ice.
The mixture was stirred at 4°C for 1 hour, and then at room
temperature for 2 hours, to which 4 M hydrochloric acid was
added dropwise to adjust pH to 6. Water (25 mL) was added
66
to the mixture, and the precipitate was collected by the
filtration, followed by being washed with water. The
precipitate was dissolved in chloroform after being dried,
which was adsorbed to silica gel. The column
chromatography was performed with ethyl acetate, and orange
crystals were obtained. Methanol was added to the crystals
to perform the reflux, followed by being left to stand at
room temperature overnight. The precipitated objective
compound was obtained as orange crystals. The yield was
370 mg (29%). Spectrum data of 1H-NMR (400 MHz, CDCl3) is
shown for the obtained compound.
5: 2.00 (t, 3H, J = 1.1 Hz), 4.57 (d, 2H, J = 6.0 Hz), 5.38
(t, 1H, J = 1.4 Hz), 5.73 (br.t, 1H), 6.16 (br.s, 1H), 6.57
(s, 1H), 7.41 (d, 2H, J = 8.5 Hz), 7.56 (t, 2H, J = 7.4
Hz), 7.63 (tt, 1H, J = 7.3 Hz, 2.4 Hz), 7.71-7.78 (m, 4H),
8.22 (s, 1H), 12.88 (s, 1H), 13.89 (s, 1H).
[0122]
The polymerizable UV-absorbing colorant obtained in
Example was copolymerized with other polymerizable monomer.
[Example 13]
0.03 parts by mass of the polymerizable UV-absorbing
colorant (HBZ-PHM) obtained in Example 1, 60 parts by mass
of 2-phenoxyethyl acrylate, 40 parts by mass of ethyl
acrylate, and 0.5 parts by mass of 2,2'-azobis(2,4-
dimethylvaleronitrile) were blended uniformly or
homogeneously, followed by being polymerized at 80°C for 40
67
minutes to manufacture a polymer sheet having a thickness
of 1 mm. The obtained polymer sheet was used as a sample
to measure the light beam transmittance at wavelengths of
220 to 800 nm. A result is shown in Fig. 1.
Further, this sample was immersed in ethanol at 40°C
for 24 hours to perform the elution treatment, and then the
light beam transmittance was measured again. As a result,
the spectrum was not changed between before and after the
elution treatment. This fact indicates that the
polymerizable UV-absorbing colorant is chemically bonded in
the material. It has been successfully confirmed that no
elution is caused after the polymerization even when the
colorant compound of the present invention is used for the
polymer synthesis by using the same together with other UV
absorber in combination. A UV-visible spectrophotometer
was used to measure the light beam transmittance (the same
was also used in the following procedures).
[0123]
The polymerizable UV-absorbing colorant obtained in
Example was copolymerized with other polymerizable monomer
together with other polymerizable UV absorber.
[Example 14]
A polymer sheet was prepared in the same manner as in
Example 13 except that 0.15 parts by mass of 2-[2'-hydroxy-
5'-(2"-methacryloyloxyethoxy)-3'-t-butylphenyl]-5-methyl-
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2H-benzotriazole was further blended as a UV absorber. The
light beam transmittance was measured at wavelengths of 220
to 800 nm in the same manner as in Example 13 by using the
obtained sheet as a sample. A result is shown in Fig. 2.
The spectrum of the light beam transmittance was not
changed between before and after the elution treatment. It
has been successfully confirmed that the polymerizable UVabsorbing
colorant of the present invention is incorporated
as the copolymer component into the polymer, and the
polymerizable UV-absorbing colorant of the present
invention is not eluted after the polymerization, even when
the polymerizable UV-absorbing colorant of the present
invention is used together with other polymerizable UV
absorber in combination.
[0124] Comparison of stability under alkaline
condition>
HBZ-PHM (1 part by weight) obtained in Example 1 and
methyl methacrylate (26 parts by weight) were changed in a
mixed solvent of dioxane (52 parts by weight), N,Ndimethylformamide
(22 parts by weight), and water (20 parts
by weight), to which 2.4 parts by weight of 2,2'-
azobis(2,4-dimethylvaleronitrile) was added, followed by
being polymerized at 75°C for 5 hours under an argon
atmosphere to obtain an HBZ-PHM copolymer.
As Comparison Example, 2,4-dihydroxy-5-(4-(2-(N-2-
methacryloyloxyethyl)carbamoyloxy)ethylphenylazo)
benzophenone (BMAC), which was synthesized in accordance
69
with a procedure disclosed in Synthesis Example 1 of Patent
Document 6 (JP2006-291006A), was used in place of HBZ-PHM
to perform a polymerization reaction in the same manner as
described above, and a BMAC copolymer was obtained.
Powders of the polymers (200 mg), which were obtained
after performing the Soxhlet extraction for 12 hours with
ethanol for powders of the respective obtained copolymers,
were suspended in ethanol (5 mL) respectively, to each of
which 4 N NaOH (5 mL) was added, followed by being stirred
at room temperature for 4 hours. The test solution in this
situation exhibited that pH was 12 to 14 with pH test
paper. After the completion of the stirring, the solution
was neutralized with 4 N HCl, to which ethanol was further
added. Insoluble matters were removed by the filtration,
and the filtrate was observed. As a result, the filtrate
was colorless and transparent in the case of the HBZ-PHM
copolymer. On the other hand, the filtrate was colored to
be yellow in the case of the BMAC copolymer. Further, Fig.
3 shows results of the measurement of the light beam
transmittances at wavelengths of 220 to 800 nm for the
respective filtrates. The filtrate of the BMAC copolymer
after the alkali treatment exhibited the transmittance
pattern which was the same as or equivalent to that of the
BMAC copolymer. This fact strongly suggests that the
colorant moiety of BMAC is eliminated from the copolymer on
account of the alkali treatment. On the other hand, any
light beam having any wavelength was transmitted through
70
the filtrate of the HBZ-PHM copolymer after the alkali
treatment, and the colorant component was not liberated or
released from the copolymer even in the case of the
condition of pH of not less than 12 brought about by the
alkali treatment. That is, it has been confirmed that the
HBZ-PHM copolymer is stable against the pH change as
compared with the BMAC copolymer, and the HBZ-PHM copolymer
is scarcely affected by the pH change.
INDUSTRIAL APPLICABILITY
[0125] According to the present invention, the
polymerizable UV-absorbing colorant monomer, which is
stable even under alkaline conditions, is provided. The
colorant compound of the present invention has, in its
molecule, the benzophenone skeleton which has the
capability to absorb the ultraviolet light, the azobenzene
skeleton which has the capability to absorb the light in
the blue region, and the polymerizable group. Therefore,
the colorant compound of the present invention can be
copolymerized with other polymerizable monomer to obtain
the polymer, and the polymer is useful as the material, for
example, for the intraocular lens.

CLAIMS
1. A compound represented by the following general
formula ( 1 ):
(in the general formula (1), R1 is a hydrogen atom, a
hydroxy group, a carboxy group, an alkyl group having 1 to
8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms,
a sulfonic acid group, or a benzyloxy group, R2 is a
hydrogen atom, a hydroxy group, or an alkoxy group having 1
to 4 carbon atoms, and R3 is represented by the following
formula (2)):
(in the general formula (2), R4 is a hydrogen atom or a
methyl group, and R5 is a single bond or an alkylene group
having 1 to 4 carbon atoms which may have a substituent or
substituents.)
2. The compound according to claim 1, wherein R1 is
a hydrogen atom, a methyl group, or an ethyl group.
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3. The compound according to claim 1 or 2, wherein
R2 is a hydrogen atom, a hydroxy group, a methoxy group, or
an ethoxy group.
4. A polymer comprising the compound as defined in
any one of claims 1 to 3 and one species or two or more
species of other polymerizable monomers which are
copolymerized with each other.
5. An intraocular lens comprising the polymer as
defined in claim 4 which is molded.