Intraocular implant having coating layer

An intraocular implant comprises a lens substrate having on the surface thereof a coating layer, the coating layer being comprised of a specific compound.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to an intraocular implant (or artificial 
substitute lens) having on its surface a coating layer. 
2. Related Background Art 
Cataracts have been hitherto treated by surgery to deliver a lens having 
turned opaque and insert an artificial lens into the lenticular capsule, 
and recovering vision after the surgery. At present, such an intraocular 
implant is prevailingly used in the "in-the-bag system" which is 
considered to cause less complication that may accompany implantation, 
i.e., a system in which the intraocular implant is inserted into the 
"lenticular capsule". 
As materials for such intraocular implants, polymethyl methacrylate is 
mainly used, and on the other hand, as materials for a lens support member 
called "haptic", polymethyl methacrylate, polyvinylidene fluoride or the 
like is used. 
The surfaces of intraocular implants are required to be hydrophilic in 
order to prevent corneal cells from being damaged or improve a lens fitted 
feeling, and methods hitherto known as means for making the surfaces of 
intraocular implants hydrophilic include a method in which the surface of 
an intraocular implant is subjected to a plasma treatment, or a method in 
which a hydrophilic coating is formed on the surface of an intraocular 
implant by plasma polymerization using monomers of a nitro compound 
represented by the general formula R-NO.sub.2 (R is a hydrocarbon). 
The method in which &he surface of an intraocular implant is subjected to a 
plasma treatment, which is a method comprising exposing the surface of an 
intraocular implant to oxygen plasma or nitrogen plasma to make its 
surface hydrophilic, has the following disadvantage. That is to say, the 
plasma treatment can achieve a uniform surface treatment with difficulty, 
and also may cause a deterioration with time wherein the hydrophilic 
nature becomes poor as time lapses. Hence, this method is not suited for 
the surface treatment& of intraocular implants which are required to be 
fitted for a long time. 
The coating or film formed by plasma polymerization of the R-NO.sub.2 
monomers can retain a superior hydrophilic nature, but a small discharge 
output applied in carrying out the polymerization may bring about an 
insufficient cross-linkage of the coating formed, resulting in an 
water-soluble film. Accordingly, a high discharge output is required for 
the formation of a non-water soluble film, and this necessarily limits 
film formation conditions to a such w high discharge output may also cause 
a slight opaqueness on the surface of the intraocular implant narrower 
scope. The film formation carried out at because of the plasma, which is 
unsuitable for the intraocular implant. 
Other methods for making the surfaces of intraocular implants hydrophilic 
include dipping and graft polymerization utilizing ultraviolet rays, both 
of which, however, are accompanied with deterioration with time, and there 
has been a problem in stability. 
On the other hand, the surfaces of intraocular implants are required to be 
capable of absorbing ultraviolet rays, harmful to retinas. For this 
purpose, U.S. Pat. No. 4,312,575, for example, discloses that a coloring 
substance may be included into the intraocular implant so that this 
coloring substance can absorb ultraviolet rays. 
However inclusion of the ultraviolet absorbing substance into an 
intraocular implant lens substrate has caused the problem that the 
mechanical strength of the intraocular implant is lowered. 
SUMMARY OF THE INVENTION 
An object of the present invention is to provide an intraocular implant 
that may suffer less deterioration with time, of the hydrophilic nature, 
has a coating laYer capable of being formed under mild film formation 
conditions for film formation, and can absorb ultraviolet rays without 
lowering the mechanical strength of the lens. 
The intraocular implant of the present invention comprises a lens substrate 
having on the surface thereof a coating layer, wherein said coating layer 
is comprised of at least one compound selected from the group consisting 
of; 
an amino compound represented by the general formula: R.sub.1 -NH.sub.2, 
wherein R.sub.1 represents a hydrocarbon group having not more than 10 
carbon atoms; 
a cyan compound represented by the general formula: R.sub.2 -CN, wherein 
R.sub.2 represents a hydrocarbon group having not more than 10 carbon 
atoms; 
an azo compound represented by the general formula: R.sub.3 
-N.dbd.N-R.sub.4, wherein R.sub.3 and R.sub.4 each represent hydrocarbon 
group having not more than 10 carbon atoms in total or hydrogen atom; and 
an amino acid represented by the general formula: R.sub.5 
-CH(NH.sub.2)COOH, wherein R.sub.5 represents a substituent constituted of 
C, H or N.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The intraocular implant of the present invention comprises a lens substrate 
having on the surface thereof a coating layer which is hydrophilic and 
capable of absorbing ultraviolet rays. As the lens substrate, 
conventionally knoWn intraocular implants can be used as they are. 
Materials preferably used for the lens substrate include, for example, 
polymethyl methacrylate, hydroxyethyl methacrylate, silicone resins, and 
polyurethane resins. 
Materials used for the coating layer of the intraocular implant of the 
present invention include an amino compound represented by the general 
formula: R.sub.1 -NH.sub.2, wherein R.sub.1 represents a hydrocarbon group 
having not more than 10 carbon atoms; a cyan compound represented by the 
general formula: R.sub.2 -CN, wherein R.sub.2 represents a hydrocarbon 
group having not more than 10 carbon atoms; an azo compound represented by 
the general formula: R.sub.3 -N.dbd.N-R.sub.4, wherein R.sub.3 and R.sub.4 
each represent hydrocarbon group having not more than 10 carbon atoms in 
total or hydrogen atom; and an amino acid represented by the general 
formula: R.sub.5 -CH(NH.sub.2)COOH, wherein R.sub.5 represents a 
substituent constituted of C, H or N. 
The above compounds can be free of any deterioration With time, of the 
hydrophilic nature and yet absorb ultraviolet rays. 
The amino compound represented by the general formula: R.sub.1 -NH.sub.2 
includes, for example, saturated or unsaturated aliphatic amino compounds 
such as aminomethane, aminoethane, 1-aminopropane, 2-aminopropane, 
1-aminobutane, 2-aminobutane, 1-amino-2-methylpropane, 
1-aminopentane,1-aminohexane, 1-aminoheptane, 1-aminooctane, 
1-aminononane, 1-aminodecane, aminoethylene, 1-aminopropene and 
1-aminobutene; saturated or unsaturated alicyclic amino compounds such as 
aminocyclopentane, aminocyclohexane, aminocycloheptane, aminocyclooctane, 
aminocyclononane, aminocyclodecane, 1-aminocyclooctene, 
1-aminocyclononene, (aminomethyl)cyclohexane and 
(aminomethyl)cycloheptane; and aromatic amino compounds such as aniline, 
o-aminotoluene, m-aminotoluene, p-aminotoluene, o-aminostyrene, 
(aminomethyl)benzene, o-(aminomethyl)toluene, 2-aminop-xylene, 
1-aminonaphthalene and 2-aminonaphthalene. 
The cyan compound represented by the general formula: R.sub.2 -CN includes, 
for example, saturated or unsaturated aliphatic cyano compounds such as 
cyanomethane, cyanoethane, cyanopropane, cyanobutane, 1-cyanopropane, 
2-cyanopropane, 1-cyanobutane, 2-cyanobutane, 1-cyano-2-methylpropane, 
1-cyanopentane, 1-cyanonhexane, 1-cyanonheptane, 1-cyanooctane, 
cyanononane, 1-cyanodecane, cyanoethylene, 1-cyanopropene and 
1-cyanobutene; saturated or unsaturated alicyclic cyan compounds such as 
cyanocylopentane, cyanocylohexane, cyanocyloheptane, cyanocylooctane, 
cyanocylononane, cyanocylodecane, 1-cyanocylooctene, 1-cyanocylononene, 
(cyanomethyl)cyclohexane and (cyanomethyl)cycloheptane; and aromatic cyan 
compounds such as benzonitrile, o-cyanotoluene, m-cyanotoluene, 
p-cyanotoluene, o-cyanostyrene, (cyanomethyl)benzene, 
o-(cyanomethyl)toluene, 2-cyano-p-xylene, 1-cyanonaphthalene and 
2-cyanonaphthalene. formula: R.sub.3 -N.dbd.N-R.sub.4 include, for 
example, both R.sub.3 and R.sub.4 saturated or unsaturated aliphatic azo 
compounds such as azomethane, azoethane, azopropane, azopentane, 
methaneazoethane, methaneazopropane, methaneazobutane, methaneazopentane, 
ethaneazopropane, ethaneazobutane, azoethylene, azopropylene, 
methneazoethylene, methneazopropylene and 2-methylpropaneazoethylene; both 
R.sub.3 and R.sub.4 saturated or unsaturated alicyclic azo compounds such 
as azocyclopropane, azocyclobutane, and cyclopropane; both R.sub.3 and 
R.sub.4 aromatic azo compounds such as azobenzene, azotoluene, azoxylene, 
p-aminoazobenzene and p-cyanazobenzene; R.sub.3 saturated or unsaturated 
aliphatic and R.sub.4 saturated or unsaturated alicyclic azo compounds 
such as methaneazocyclopropane, ethaneazocyclobutane, 
ethyleneazocyclopropane and propyleneazocyclopropane; R.sub.3 saturated or 
unsaturated aliphatic and R.sub.4 aromatic azo compounds such as 
methaneazobenzene, ethaneazoxylene and ethyleneazostyrene; and R.sub.3 
alicyclic and R.sub.4 aromatic azo compounds such as 
cyclopropaneazobenzene, cyclopenteneazoxylene and cyclopropeneazotoluene. 
The amino acid represented by the general formula: R.sub.5 
-CH(NH.sub.2)COOH include, for example, aliphatic amino acids such as 
glycine, alanine, valine, serine and asparagine; amino acids having an 
aromatic ring, such as phenylalanine; and amino acids having a 
heterocyclic ring, such as histidine. 
In the present invention, the above compounds can be used alone or in 
combination of two or more kinds. A carbon atom number of more than 11 in 
total, contained in R.sub.3 and R.sub.4, or a carbon atom number of more 
than 11 in each of R.sub.1 and R.sub.2 may result in an insufficient 
hydrophilic nature of the resulting coating. 
The coating layer comprising the above compound(s) has a higher cross-link 
density and better barrier properties than those of the lens substrate, so 
that the free monomers contained in the lens substrate can be prevented 
from dissolving therefrom into an eye. Of the above compounds, the amino 
acids are particularly preferred because of their superior compatibility 
with organisms. 
The coating layer of the present invention is formed by plasma 
polymerization or vacuum deposition polymerization using monomers of the 
above compound(s). 
The plasma polymerization in the present invention can be carried out, for 
example, by using the apparatus as illustrated in FIG. 1 or 2, but the 
apparatus are by no means limited to these and any commonly available 
plasma polymerization apparatus can be used without difficulty. 
In the apparatus of an internal electrode type as illustrated in FIG. 1, a 
pair of electrodes 2a and 2b opposed each other are provided in a reaction 
vessel 1, and a lens substrate S is placed between them. The electrode 2b 
is connected to an electric source through a lead wire 3. The inside of 
the reaction vessel 1 is evacuated through an exhaust vent 4 to which a 
vacuum pump is connected, and monomers are fed from a monomer feed pipe 5. 
Film formation is carried out by generating plasma between the electrodes 
2a and 2b, where, for example, the temperature of the lens substrate S can 
be controlled by feeding a cooling water from an inlet 6 and discharging 
it from an outlet 7 in instances in Which the lens substrate S is placed 
on the lower electrode 2a. 
Plasma polymerization conditions in this instance may be arbitrarily 
selected based on conditions employed in ordinary plasma polymerization 
reactions. For example, the inside of the reaction vessel is evacuated to 
a vacuum of 1.times.10.sup.-3 Torr, and thereafter monomers are introduced 
into the reaction vessel 1 at a flow rate of not more than 100 SCCM, and 
preferably not more than 20 SCCM, per minute, and the pressure is 
controlled to be approximately from 0.01 to 10 Torr. Under such 
conditions, an inert gas may be introduced into the reaction vessel 1. In 
carrying out this reaction, the discharge output may be set to not more 
than 300 W. and preferably not more than 100 W. The coating formed on the 
lens substrate S may have a thickness usually from 50 to 2,000 .ANG., and 
preferably from 50 to 3,000 .ANG., in approximation. The polymerization 
can be completed usually in 10 minutes or less. 
In the apparatus of a non-electrode type as illustrated in FIG. 2, a coil 
electrode 11 is provided on one end of a reaction vessel -0, and the 
inside of the reaction vessel is evacuated from an exhaust vent 12 to 
which a vacuum pump is connected from the side opposite to the coil 
electrode 11. Then an inert carrier gas as exemplified by argon and helium 
is fed from a carrier gas feed pipe 13 and an electric current is flowed 
to the coil electrode 11, thereby generating plasma. This plasma activates 
in the reaction vessel the monomers fed from the feed pipe 14, and thus a 
coating is formed on the lens substrate S. The carrier gas is introduced 
into a reaction vessel 10 so that the dissociation of the monomer gas can 
be suppressed. The energy source for the generation of plasma may be of 
either direct current or alternate current. The state in which the lens 
substrate S is set may be changed (for example, the lens may be reversed) 
so that the whole surface of the substrate S can be uniformly provided 
with the coating layer. 
A typical example for carrying out the vacuum depositIon polymerization in 
the present invention by using the vacuum deposition polymerization 
apparatus as illustrated in FIG. 3 will be descrIbed below but by no means 
limited to this. In the case of this vacuum deposition polymerization 
apparatus, the inside of the reaction vessel 20 is evacuated from an 
exhaust vent 21. Monomer containers 22 in which monomers are put are 
heated with halogen lamps 23 to vaporize the monomers, thereby forming a 
coating on the lens substrate S. The thickness of the coating can be 
controlled by monitoring it using a monitor 24 to open or shut a shutter 
25. The numeral 26 denotes a partition wall. 
In this instance, for example, the inside of the reaction vessel 20 is 
evacuated to a vacuum of not more than 5.times.10.sup.-4 Torr, and 
monomers are heated to a temperature at which they are sufficiently 
vaporized in the reaction vessel 20. The film formation is carried out 
while opening or shutting the shutter 25. The coating formed on the 
surface of the substrate lens 20 may have a thickness of from 50 to 20,000 
.ANG., and preferably from 50 to 3,000 .ANG., in approximation, which can 
be formed usually within several ten minutes. A heat treatment may also be 
carried out after the coating has been formed, but it must be applied in 
the extent that the lens substrate S may not be affected adversely. 
The lens substrate used in the present invention comprises PMMA, HEMA, 
silicone rubber, or &he like as previously described, and &he lens 
substrates made of these have a compatibility with organisms Which is 
preferable as the intraocular implant. These lens substrates may also be 
subjected to any desired treatment before the coating is formed thereon, 
without causing any difficulties. Such a treatment include, for example, 
an argon plasma treatment. 
EXAMPLES 
The effect of the present invention will become apparent from Examples set 
out below, but the scope of a right on the present invention is by no 
means limited to these Examples. 
EXAMPLE 1 
A PMMA lens With a thickness of 1 mm at maximum and a diameter of 7 mm was 
set as the lens substrate S in the plasma polymerization apparatus as 
illustrated in FIG. 1. The inside of the reaction vessel 1 was evacuated 
to a vacuum of 1.times.10.sup.-6 Torr, and thereafter, while allylamine 
was fed from the monomer feed pipe 6 at a rate of 10 cc per minute, the 
pressure inside the reaction vessel 1 was controlled to be 
1.times.10.sup.-1 Torr. Then, While the temperature of the lens substrate 
S was maintained at 30.degree. C., a high frequency electric power of 
13.56 MHz was applied to the electrode 2b. The discharge output was 70 W, 
under which the plasma polymerization was carried out for 10 minutes. As a 
result, there was obtained an intraocular implant having on its surface a 
coating layer with a thickness of 1,000 .ANG.. 
The hydrophilic nature of the resulting intraocular implant was determined 
by measuring a contact angle to water using a dropping method for every 
prescribed days lapsed. On this intraocular implant, also measured Was 
transmittance of light with wavelengths of from 250 to 850 nm to determine 
the transmittances of visible light and ultraviolet light. The measurement 
results are shown in Tables 1 and 2. 
Example 2 
A silicone resin lens with a thickness of 1 mm at maximum and a diameter of 
7 mm was set as the lens substrate S in the plasma polymerization 
apparatus as illustrated in FIG. 2. The inside of the reaction vessel 1 
was evacuated to a vacuum of 1.times.10.sup.-6 Torr, and thereafter, while 
argon gas was fed from the carrier gas feed pipe 13 at a rate of 10 SCCM 
per minute and acetonitrile monomers were fed from the monomer feed pipe 6 
at a rate of 10 cc per minute, the pressure inside the reaction vessel 10 
was controlled to be 2.times.10.sup.-1 Torr. A high frequency electric 
power of 13.56 MHz was applied to the coil electrodes 11 to generate 
plasma. The discharge output was 50 W, under which the plasma 
polymerization was carried out for 10 minutes. As a result, there was 
obtained an intraocular implant having on its surface a coating layer with 
a thickness of 1,000 .ANG.. 
On the resulting intraocular implant the contact angle and transmittance 
were measured in the same manner as Example 1. The measurement results are 
shown in Tables 1 and 2. 
EXAMPLE 3 
In the same manner as Example 2, plasma polymerization was carried out 
using azoethane as monomers, to prepare an intraocular implant. 
Polymerization conditions and lens substrate were the same as used in 
Example 2. The contact angle and transmittance were measured to obtain the 
results as shown in Tables 1 and 2. 
EXAMPLE 4 
In the same manner as Example 2, plasma polymerization was carried out 
using glycine as monomers, to prepare an intraocular implant. 
Polymerization conditions and lens substrate were the same as used in 
Example 2. The contact angle and transmittance were measured to obtain the 
results as shown in Tables 1 and 2. 
EXAMPLE 5 
In the same manner as Example 1, plasma polymerization was carried out 
using an HEMA lens with a thickness of 1 mm in thickness at maximum and a 
diameter of 7 mm as the lens substrate S and also using allylamine as 
monomers, to prepare an intraocular implant. Polymerization conditions 
were the same as used in Example 1. The contact angle and transmittance 
were measured to obtain the results as shown in Tables 1 and 2. 
EXAMPLE 6 
A PMMA lens with a thickness of 1 mm at maximum and a diameter of 7 mm was 
set as the lens substrate S in the vacuum deposition polymerization 
apparatus as illustrated in FIG. 3. The inside of the reaction vessel I 
was evacuated to a vacuum of 5.times.10.sup.-6 Torr, allylamine monomers 
in &he monomer containers 22 were heated to 200.degree. C. to evaporate 
them, and the shutter 25 was kept open for 5 minutes, thus prepared an 
intraocular implant having on its surface a coating layer. The contact 
angle and transmittance of this intraocular implant were measured to 
obtain the results as shown in Tables 1 and 2. 
EXAMPLE 7 
In the same manner as Example 6, vacuum deposition polymerization was 
carried out using a silicone rubber lens with a thickness of 1 mm in 
thickness at maximum and a diameter of 7 mm as the lens substrate S, to 
prepare an intraocular implant. Polymerization conditions and lens 
substrate were the same as used in Example 6. The contact angle and 
transmittance were measured to obtain the results as shown in Tables 1 and 
2. 
COMATIVE EXAMPLE 1 
In the same manner as Example 1, plasma polymerization was carried out 
using nitroethane as monomers, to prepare an intraocular implant. The 
polymerization conditions and lens substrate were the same as used in 
Example 1. The contact angle and transmittance were measured to obtain the 
results as shown in Tables 1 and 2. 
COMATIVE EXAMPLE 2 
In the same manner as Example 1, plasma polymerization was carried out 
using nitroethane as monomers, to prepare an intraocular implant. The 
polymerization conditions and lens substrate were the same as used in 
Example 2. The contact angle and transmittance were measured to obtain the 
results as shown in Tables 1 and 2. 
COMATIVE EXAMPLE 3 
A PMMA lens with a thickness of 1 mm at maximum and a diameter of 7 mm was 
set as the lens substrate S in the plasma polymerization apparatus as 
illustrated in FIG. 1. The inside of the reaction vessel 1 was evacuated 
to a vacuum of 1.times.10.sup.-6 Torr, and thereafter, while nitrogen gas 
was fed from the carrier gas feed pipe 6 at a rate of 10 cc per minute, 
the pressure inside the reaction vessel 1 was controlled to be 
3.times.10.sup.-1 Torr. While maintaining the substrate temperature at 
30.degree. C., a high frequency electric power of 13.56 MHz was applied to 
the coil electrodes 11 to generate plasma. The discharge output was 50 W, 
under which the plasma polymerization was carrier out for 2 minutes, thus 
obtained an intraocular implant having on its surface a coating layer. 
For the resulting intraocular implant, the contact angle and transmittance 
were measured to obtain the results as shown in Tables 1 and 2. 
COMATIVE EXAMPLE 4 
In the same manner as Comparative Example 3, plasma treatment was carried 
out using a silicone resin lens with a thickness of 1 mm in thickness at 
maximum and a diameter of 7 mm as the lens substrate S, to prepare an 
intraocular implant. Discharge conditions and gases were the same as used 
in Comparative Example 3. The contact angle and transmittance were 
measured to obtain the results as shown in Tables 1 and 2. 
COMATIVE EXAMPLE 5 
Contact angle and transmittance of a control silicone rubber substrate 
(with a thickness of 1 mm in thickness at maximum and a diameter of 7 mm) 
were measured. The measurement results are shown in Tables 1 and 2. 
COMATIVE EXAMPLE 6 
Contact angle and transmittance of a PMMA substrate (with a thickness of 1 
mm in thickness at maximum and a diameter of 7 mm) were measured. The 
measurement results are shown in Tables 1 and 2. 
EXAMPLE 8 
Using allylamine as monomers, a coating layer was uniformly formed in the 
same manner as Example 2 on the whole surface of a substrate comprising 
silicone resin having a diameter of 10 mm and a thickness of 0.3 mm, thus 
prepared a sample. On this sample, water was dropped and a rubbing test 
was carried out by backward and forward rubbing it 10 times with tissue 
paper for lens under application of a load of 10 g. A similar rubbing test 
was also carried out using isopropyl alcohol (IPA). 
COMATIVE EXAMPLE 7 
The same test as Example 8 was carried out for a control silicone resin 
substrate having a diameter of 10 mm and a thickness of 0.3 mm. 
The test results in these Example 8 and Comparative Example 7 are shown in 
Table 3, in which the sample having caused clouding is evaluated as "O", 
and the one having caused no clouding, as "X". 
TABLE 1 
______________________________________ 
Contact angle (.theta..degree.) 
Days lapsed: 
0 2 5 10 30 100 200 
______________________________________ 
Example 1 
32 34 35 36 36 36 36 
Example 2 
48 50 51 52 52 52 52 
Example 3 
45 48 50 51 51 51 51 
Example 4 
47 50 51 52 52 52 52 
Example 5 
38 41 42 42 42 42 42 
Example 6 
32 35 37 38 38 38 38 
Example 7 
35 38 41 42 43 43 43 
Comparative 
Coating dissolved in water 
Example 1 
Example 2 
Coating dissolved in water 
Example 3 
40 64 65 65 65 65 65 
Example 4 
40 120 120 120 120 120 120 
Example 5 
120 120 120 120 120 120 120 
Example 6 
65 65 65 65 65 65 65 
______________________________________ 
TABLE 2 
______________________________________ 
Wavelength: 
Transmittance (%) 
(nm) 850 600 450 400 350 300 250 
______________________________________ 
Example 1 
91 90 85 80 70 6 5 
Example 2 
92 92 90 78 69 42 22 
Example 3 
91 91 90 76 58 40 21 
Example 4 
92 92 90 77 59 44 30 
Example 5 
92 92 87 80 68 52 5 
Example 6 
90 90 90 86 55 15 5 
Example 7 
91 91 91 90 84 40 14 
Comparative 
90 90 90 90 90 80 5 
Example 1 
Comparative 
92 92 92 92 92 82 72 
Example 2 
Comparative 
92 92 92 92 92 85 5 
Example 3 
Comparative 
94 94 93 93 92 90 80 
Example 4 
Comparative 
94 94 93 93 92 90 80 
Example 5 
Comparative 
92 92 92 92 92 85 5 
Example 6 
______________________________________ 
TABLE 3 
______________________________________ 
Water IPA 
______________________________________ 
Example 8 .circle. 
.circle. 
Comparative Example 7 
.circle. 
X 
______________________________________ 
As described in the above, the intraocular implant of the present invention 
has the following advantages. 
(1) A stable hydrophilic nature free of deterioration with time can be 
attained. 
(2) The hydrophilic nature and ultraviolet light screening properties can 
be concurrently attained without any lowering of mechanical strength of 
lenses. 
(3) Because of a higher cross-link degree and better barrier properties of 
the coating layer as compared with the substrate, it does not occur that 
the free monomers in the lens substrate dissolve into an eye.