U.S. patent application number 09/875410 was filed with the patent office on 2002-06-27 for optically clear reinforced silicone elastomers of high optical refractive index and improved mechanical properties for use in intraocular lenses.
This patent application is currently assigned to Allergan. Invention is credited to Christ, Richard, Nash, Brian Allen, Petraitis, Del Joseph.
Application Number | 20020082691 09/875410 |
Document ID | / |
Family ID | 27486053 |
Filed Date | 2002-06-27 |
United States Patent
Application |
20020082691 |
Kind Code |
A1 |
Christ, Richard ; et
al. |
June 27, 2002 |
Optically clear reinforced silicone elastomers of high optical
refractive index and improved mechanical properties for use in
intraocular lenses
Abstract
Optically clear, reinforced cross-linked silicone elastomers of
the invention contain 12 to 18 mol percent of aryl substituted
siloxane units of the formula R.sub.4,R.sub.5--SiO, end blockers
containing silioxane units of the formula
R.sub.1R.sub.2R.sub.3--Si--O, and dialkyl siloxane units of the
formula R.sub.6R.sub.7--Si--O R.sub.1 and R.sub.2 are alkyl, aryl
or substituted alkyl or substituted aryl groups, and R.sub.3 is an
alkenyl group. R.sub.4 and R.sub.5 are phenyl or mono lower alkyl
substituted phenyl groups. R.sub.6 and R.sub.7 are methyl or ethyl
groups. The polymer has a degree of polymerization between 100 to
2000, and preferably approximately 250. The polymer also contains
trimethyl silyl treated silica as a reinforcer in the weight ratio
of approximately 15 to 45 parts of reinforcer to 100 parts of the
polymer. After cross-linking, the polymer has properties of an
optical refractive index which is at least 1.44, a type A durometer
hardness of at least 35, tensile strength of at least 500 psi and
tear strength of at least 20 phi. The foregoing properties render
the cross-linked polymer especially suitable for forming the bodies
of intraocular lenses.
Inventors: |
Christ, Richard; (Orange,
CA) ; Nash, Brian Allen; (Carpinteria, CA) ;
Petraitis, Del Joseph; (Goleta, CA) |
Correspondence
Address: |
Frank J. Uxa
Stout, Uxa, Buyan & Mullins, LLP
Suite 300
4 Venture
Irvine
CA
92618
US
|
Assignee: |
Allergan
Waco
TX
|
Family ID: |
27486053 |
Appl. No.: |
09/875410 |
Filed: |
June 5, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09875410 |
Jun 5, 2001 |
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09174267 |
Oct 16, 1998 |
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09174267 |
Oct 16, 1998 |
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08866292 |
May 28, 1997 |
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08866292 |
May 28, 1997 |
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08572768 |
Dec 15, 1995 |
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08572768 |
Dec 15, 1995 |
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08315279 |
Sep 29, 1994 |
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08315279 |
Sep 29, 1994 |
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08086763 |
Jun 30, 1993 |
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08086763 |
Jun 30, 1993 |
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07870799 |
Apr 17, 1992 |
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07870799 |
Apr 17, 1992 |
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07562452 |
Aug 1, 1990 |
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07562452 |
Aug 1, 1990 |
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07292212 |
Dec 29, 1988 |
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07292212 |
Dec 29, 1988 |
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07011021 |
Feb 5, 1987 |
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Current U.S.
Class: |
623/6.56 ;
523/212; 524/493 |
Current CPC
Class: |
A61L 27/446 20130101;
C08G 77/34 20130101; A61L 2430/16 20130101; C08K 3/36 20130101;
C08L 83/04 20130101; C08L 83/04 20130101; C08L 83/04 20130101; C08L
83/04 20130101; A61F 2/16 20130101; A61L 27/446 20130101; C08K 3/36
20130101; C08G 77/04 20130101; C08K 3/36 20130101; A61F 2/16
20130101; A61L 27/40 20130101; G02B 1/043 20130101; A61L 27/446
20130101; G02B 1/043 20130101 |
Class at
Publication: |
623/6.56 ;
523/212; 524/493 |
International
Class: |
A61F 002/16; C08K
009/06 |
Claims
What is claimed is:
1. An optically clear, reinforced cross-linked silicone elastomer,
comprising: a polymer containing 12 to 18 mol percent diphenyl
siloxane units, and end blockers containing siloxane units of the
formula R.sub.1,R.sub.2,R.sub.3--Si--O wherein R.sub.1 and R.sub.2
are alkyl, aryl or substituted alkyl or substituted aryl group,
R.sub.1 and R.sub.2 being either identical or different from one
another and wherein R.sub.3 is an alkenyl group, the balance of the
polymer consisting of dimethyl siloxane units, the polymer having a
degree of polymerization approximately between 100 to 2000, and the
polymer having been cured by cross linking; a trimethyl silyl
treated silica reinforcer finely dispersed in the polymer, the
elastomer having the physical properties of: an optical refractive
index which is at least 1.44; a Type A durometer hardness value of
at least 35; a tensile strength of at least 500 psi, and a tear
strength of at least 20 pli.
2. The silicone elastomer of claim 1 wherein the R.sub.1 and
R.sub.2 groups of the end blocking siloxane units are methyl, and
the R.sub.3 group of the end blocking siloxane unit is vinyl.
3. The silicone elastomer of claim 2 wherein the polymer contains
approximately 14 to 16 mol percent diphenyl siloxane units.
4. The silicone elastomer of claim 3 wherein the polymer contains
approximately 15 mol percent diphenyl siloxane units.
5. The silicone elastomer of Claim 3 wherein the optical refractive
index is at least 1.459.
6. The silicone elastomer of claim 3 wherein the ratio of polymer
to the trimethyl silyl treated silica reinforcer is approximately
15 to 45 parts by weight of the reinforcer to 100 parts by weight
of the polymer.
7. The silicone elastomer of claim 6 wherein the ratio of polymer
to the trimethyl silyl treated silica reinforcer is approximately
27 parts of the reinforcer to 100 parts of the polymer.
8. The silicone elastomer of claim 3 having a type A durometer
hardness value of approximately 38 to 40, a tensile strength of
approximately 700 to 750 psi, and a tear strength of approximately
40 pli.
9. The silicone elastomer of claim 3 wherein the degree of
polymerization is approximately 250 .
10. An optically clear, reinforced cross-linked silicone elastomer,
comprising: a polymer containing 12 to 18 mol percent of aryl
substituted siloxane units of the formula R.sub.4,R.sub.5--Si--O
wherein R.sub.4 and R.sub.5 are identical with one another or are
different from one another and represent phenyl, or mono- or di-
lower alkyl substituted phenyl groups, and end blockers containing
siloxane units of the formula R.sub.1,R.sub.2,R.sub.3--Si--O
wherein R.sub.1 and R.sub.2 are alkyl, aryl or substituted alkyl or
substituted aryl group, R.sub.1 and R.sub.2 being either identical
or different from one another and wherein R.sub.3 is an alkenyl
group, the balance of the polymer consisting of dialkyl siloxane
units of the formula R.sub.6,R.sub.7--Si--O wherein R.sub.6 and
R.sub.7 are identical with one another or are different from one
another and are methyl or ethyl groups, the polymer having a degree
of polymerization approximately between 100 to 2000, and the
polymer having been cured by cross linking; a trimethyl silyl
treated silica reinforcer finely dispersed in the polymer, the
cross-linked elastomer having the physical properties of: an
optical refractive index which is at least 1.44; a Type A durometer
hardness value of at least 35; a tensile strength of at least 500
psi, and a tear strength of at least 20 pli.
11. The elastomer of claim 10 wherein the R.sub.4 and R.sub.5
groups are phenyl groups.
12. The elastomer of claim 10 wherein the R.sub.1 and R.sub.2
groups are methyl.
13. The elastomer of claim 10 wherein the R.sub.1 And R.sub.2
groups are methyl, the R.sub.3 group is vinyl.
14. The elastomer of claim 10 wherein the R.sub.6 and R.sub.7
groups are methyl.
15. The elastomer of claim 10 wherein the degree of polymerization
is approximately 250 .
16. The elastomer of claim 10 wherein the ratio of the reinforcer
to the polymer is approximately 15 to 45 part per weight for 100
parts of the polymer.
17. The elastomer of claim 10 further comprising a ultra violet
light absorbing agent covalently linked to the cross linked
elastomer.
18. An optically clear, reinforced polyayloxane base comprising: a
copolymer having 12 to 18 mol percent diphenyl siloxane units, and
end blockers containing siloxane units of the formula
R.sub.1,R.sub.2,R.sub.3- --Si--O wherein R.sub.1 and R.sub.2 are
alkyl, aryl or substituted alkyl or substituted aryl group, R.sub.1
and R.sub.2 being either identical or different from one another
and wherein R.sub.3 is an alkenyl group, the balance consisting of
dimethyl siloxane units, the polymer having a degree of
polymerization approximately between 100 to 2000; a trimethyl silyl
treated silica reinforcer finely dispersed in the copolymer, the
weight ratio of the reinforcer to the copolymer being approximately
15 to 45 parts for 100 parts of the copolymer, the base having an
optical refractive index of at least 1.44 and a viscosity of
approximately 35,000 to 80,000 cp and is capable of being cured by
cross-linking such that the physical properties of the cured
cross-linked base include: an optical refractive index which is at
least 1.44; a Type A durometer hardness value of at least 35; a
tensile strength of at least 500 psi, and a tear strength of at
least 20 pli.
19. The base of claim 18 wherein R.sub.1 and R.sub.2 are methyl,
and R.sub.3 is vinyl.
20. The base of claim 19 wherein the degree of polymerization of
the copolymer is approximately 250 .
21. The base of claim 19 wherein the weight ratio of the reinforcer
to the copolymer in approximately 27 parts for 100 parts of the
polymer.
22. The base of claim 19 wherein the copolymer comprises
approximately 15 mol percent diphenyl siloxane units.
23. The base of claim 22 having an optical refractive index of at
least 1.459.
24. An optically clear, reinforced polysiloxane base consisting
essentially of: a copolymer having 12 to 18 mol percent of aryl
substituted siloxane units of the formula R.sub.4,R.sub.5--Si--O
wherein R.sub.4 and R.sub.5 are identical with one another or are
different iron one another and represent phenyl, or mono- or di-
lower alkyl substituted phenyl groups, and end blockers containing
siloxane units of the formula R.sub.1,R.sub.2,R.sub.3--Si--O
wherein R.sub.1 and R.sub.2 are alkyl, aryl or substituted alkyl or
substituted aryl group, R.sub.1 and R.sub.2 being either identical
or different from one another and wherein R.sub.3 is an alkenyl
group, the balance of the polymer consisting of dialkyl siloxane
units of the formula R.sub.6,R.sub.7--Si--O wherein R.sub.6 and
R.sub.7 are identical with one another or are different from one
another and are methyl or ethyl groups, the polymer having a degree
of polymerization approximately between 100 to 2000; a trimethyl
silyl treated silica reinforcer finely dispersed in the copolymer,
the weight ratio of the reinforcer to the copolymer being
approximately 15 to 45 parts for 100 parts of the copolymer, the
base having an optical refractive index of at least 1.44 and a
viscosity of approximately 35,000 to 80,000 cp and is capable of
being cured by cross-linking such that the physical properties of
the cured cross-linked base include: an optical refractive index
which is at least 1.44; a Type A durometer hardness value of at
least 35; a tensile strength of at least 500 psi, and a tear
strength of at least 20 pli.
25. The base of claim 24 wherein the R.sub.4 and R.sub.5 groups are
both phenyl.
26. The base of claim 24 wherein the R.sub.1 and R.sub.2 units are
both methyl and R.sub.3 is vinyl.
27. The base of claim 24 wherein the R.sub.6 and R.sub.7 units are
both methyl.
28. The base of claim 24 wherein the R.sub.4 and R.sub.5 groups are
both phenyl, R.sub.1, R.sub.2, R.sub.6 and R.sub.7 are methyl and
R.sub.3 is vinyl, and wherein the copolymer contains approximately
15 mol percent diphenyl siloxane units.
29. The base of claim 28 wherein the weight ratio of the reinforcer
to the base is approximately 27 parts of the reinforcer to 100
parts of the copolymer, and wherein the degree of polymerization of
the copolymer is approximately 250 .
30. The base of claim 29 having an optical refractive index of at
least 1.459.
31. An intraocular lens body suitable for surgical implantation
into the human eye, the lens body being an optically clear
reinforced cross-linked silicone elastomer which comprises: a
polymer containing 12 to 18 mol percent diphenyl siloxane units,
and end blockers containing siloxane units of the formula
R.sub.1,R.sub.2,R.sub.3--Si--O wherein R.sub.1 and R.sub.2 are
alkyl, aryl or substituted alkyl or substituted aryl group, R.sub.1
and R.sub.2 being either identical or different from one another
and wherein R.sub.3 is an alkenyl group, the balance of the polymer
consisting of dimethyl siloxane units, the polymer having a degree
of polymerization approximately between 100 to 2000; a trimethyl
silyl treated silica reinforcer finely dispersed in the polymer,
the reinforcer having a weight ratio of approximately 15 to 45
parts to 100 part of the polymer, the lens body having the physical
properties of: an optical refractive index which is at least 1.44;
a Type A durometer hardness value of at least 35; a tensile
strength of at least 500 psi, and a tear strength of at least 20
pli.
32. The intraocular lens of claim 31 wherein the R.sub.1 and
R.sub.2 groups of the end blocking siloxane units of the polymer
are methyl, and the R.sub.3 group of the end blocking siloxane unit
is vinyl and wherein the polymer contains approximately 14 to 16
mol percent diphenyl siloxane units.
33. The intraocular lens of claim 32 wherein the polymer contains
approximately 15 mol percent diphenyl siloxane units, has a degree
of polymerization of approximately 250, the ratio of polymer to the
trimethyl silyl treated silica reinforcer is approximately 27 parts
of the reinforcer to 100 parts of the polymer and wherein the
optical refractive index of the lens body is at least 1.459.
34. The intraocular lens of claim 33 having a type A durometer
hardness value of approximately 38 to 40, a tensile strength of
approximately 700 to 750 psi, and a tear strength of approximately
40 pli.
35. An intraocular lens body suitable for surgical implantation
into the human eye, the lens body being an optically clear
reinforced cross-linked silicone elastomer which comprises: a
polymer containing 12 to 18 mol percent of aryl substituted
siloxane units of the formula R.sub.4,R.sub.5--Si--O wherein
R.sub.4 and R.sub.5 are identical with one another or are different
from one another and represent phenyl, or mono- or di- lower alkyl
substituted phenyl groups, and end blockers containing siloxane
units of the formula R.sub.1,R.sub.2,R.sub.3--Si--O wherein R.sub.1
and R.sub.2 are alkyl, aryl or substituted alkyl or substituted
aryl group, R.sub.1 and R.sub.2 being either identical or different
from one another and wherein R.sub.3 is an alkenyl group, the
balance of the polymer consisting of dialkyl siloxane units of the
formula R.sub.6,R.sub.7--Si--O wherein R.sub.6 and R.sub.7 are
identical with one another or are different from one another and
are methyl or ethyl groups, the polymer having a degree of
polymerization approximately between 100 to 2000; a trimethyl silyl
treated silica reinforcer finely dispersed in the polymer, the
reinforcer having a weight ratio of approximately 15 to 45 parts to
100 part of the polymer, the lens body having the physical
properties of: an optical refractive index which is at least 1.44;
a Type A durometer hardness value of at least 35; a tensile
strength of at least 500 psi, and a tear strength of at least 20
pli.
36. The intraocular lens of claim 10 wherein the R.sub.4 and
R.sub.5 groups are phenyl groups, the R.sub.1 and R.sub.2 groups
are methyl, the R.sub.3 group is vinyl, and the R.sub.6 and R.sub.7
groups are methyl.
37. The intraocular lens of claim 36 wherein the polymer has a
degree of polymerization of approximately 250 .
38. The intraocular lens of claim 36 wherein the ratio of the
reinforcer to the polymer is approximately 27 parts per weight of
the reinforcer for 100 parts per weight of the polymer.
39. The intraocular lens of claim 36 further comprising a ultra
violet light absorbing agent covalently linked to the cross linked
elastomer.
40. The intraocular lens of claim 38 having a type A durometer
hardness value of approximately 38 to 40, a tensile strength of
approximately 700 to 750 psi, and a tear strength of approximately
40 pli.
Description
[0001] Intraocular lenses made from silicone polymeric materials
are usually deformable, so that for implantation a smaller incision
needs to be surgically out in the eye than for the implantation of
"hard" intraocular lenses. In this respect, the size and mechanical
characteristics of the silicone polymeric intraocular lenses play
an important role. As it will be well understood by those skilled
in the art, for successful implantation the lens rust have
sufficent structural integrity, elasticity and small enough size to
permit the folding for insertion through a small incision. After
insertion, the lens must, of course, regain its original molded
shape.
[0002] It will be further understood by those skilled in the art
that the thinner is the lens, the easier is the surgical insertion
procedure. On the other hand, in order to function as an
intraocular lens, the lens material must have sufficient optical
refractory power. Consequently, the higher is the optical
refractive index of the silicone material, the thinner can be the
lens to obtain the same optical refractory power.
[0003] Some silicone polymeric materials described in the prior art
contain a silica reinforcer finely distributed in the polymeric
silicone resin. Usually such reinforcement of the silicone
polymeric material with silica is necessary for the polymeric
material to attain adequate structural strength to be used as a
foldable intraocular lens. Such silica reinforced polymeric
silicone resins suitable for use as soft contact or intraocular
lenses are described in U.S. Pat. Nos. 3,996,187; 4,615,702;
3,996,189. Additional disclosures relating to polymeric silicone
materials or silica reinforcers, which comprise the background of
the present invention can be found in U.S. Pat. Nos. 3,341,490;
3,284,406; 3,457,214; and in European Patent Application No.
0110537 filed on Oct. 18, 1983.
[0004] Additional disclosures relating to intraocular lenses can be
found in U.S. Pat. No. 4,573,998, published UK Patent Application
GB 2114315, and in co-pending application for U.S. patent Ser. No.
946,703 filed on Dec. 24, 1986 by Reich et. al. The latter U.S.
patent application is assigned to one of the co-assignees of the
present applications
[0005] The prior art intraocular lenses made of silica reinforced
silicone copolymers still do not fully satisfy the need for high
enough optical refractory power to permit sufficently thin lens
size which in turn would make it possible to surgically implant the
lens through a desirably small incision in the eye. In other words,
there is still need in the art for reinforced silicone polymeric
materials which have sufficiently high optical clarity, refractive
index, durometer hardness, tensile strength and related mechanical
properties to permit construction of thin foldable intraocular
lenses. The present invention satisfies this need.
SUMMARY OF THE INVENTION
[0006] It is an object of the present invention to provide
optically clear reinforced silicone polymeric materials of a
refractive index of at least 1.44 coupled with sufficient durometer
hardness, tensile strength and other mechanical properties to
permit forming of thin intraocular lenses through final
cross-linking of the polymeric material into desired lens
shapes.
[0007] It is another object of the present invention to provide a
thin intraocular lens body from a reinforced silicone polymeric
material, wherein the lens body has an optical refractive index of
at least 1.44 and sufficient mechanical properties to permit
implantation through a small incision in the eye.
[0008] The foregoing objects and advantages are attained by an
optically clear, reinforced cross-linked silicone elastomer which
includes a polymer containing 12 to 18 mol percent of aryl
substituted siloxane units of the formula R.sub.4,R.sub.5--Si--O.
In the formula R.sub.4 and R.sub.5 are identical with one another
or are different from one another and represent phenyl, or mono-
lower alkyl substituted phenyl groups, or di- lower alkyl
substituted phenyl groups. Preferably both R.sub.4 and R.sub.5 are
phenyl.
[0009] The polymer has end blockers containing siloxane units of
the formula R.sub.1,R.sub.2,R.sub.3--Si--O wherein R.sub.1 and
R.sub.2 are alkyl, aryl or substituted alkyl or substituted aryl
groups, and R.sub.1 and R.sub.2 may be identical or different from
one another. The R.sub.3 group of the end blocking siloxane units
in an alkenyl group. Preferably, the end blocker is a dimethylvinyl
siloxane unit.
[0010] The balance of the polymer consists of dialkyl siloxane
units of the formula R.sub.6,R.sub.7--Si--O wherein R.sub.6 and
R.sub.7 are identical with one another or are different from one
another and are methyl or ethyl groups, and the polymer has a
degree of polymerization approximately between 100 to 2000.
Preferably, the R.sub.6 and R units are both methyl, and the degree
of polymerization is approximately 250.
[0011] A trimethyl silyl treated silica reinforcer is finely
dispersed in the polymer, in a weight ratio of approximately 15 to
45 parts of the reinforcer to 100 parts of the polymer. Preferably,
there is approximately 27 parts of reinforcer to 100 parts of the
copolymer.
[0012] The polymer when cured by cross-linking in a mold forms the
body of an intraocular lens of the invention, and has the
properties of an optical refractive index which is at least 1.44, a
type A durometer hardness value of at least 35, a tensile strength
of at least 500 psi, and a tear strength of at least 20 pli.
[0013] Further objects and advantages of the present invention will
become readily apparent from the ensuing description wherein the
specific embodiments are described as follows.
DESCRIPTION OF THE SPECIFIC EMBODIMENTS
[0014] Reinforced elastomeric polysiloxane copolymer compositions
are provided in accordance with the present invention, which after
appropriate curing by cross-linking, are eminently suitable to
serve as the body of foldable "soft" intraocular lenses capable of
implantation through a small incision in the eye.
[0015] More particularly, the reinforced elastomeric composition of
the present invention has the chemical composition of a
cross-linked copolymer including approximately 12 to 18 mol per
cent of aryl substituted siloxane units of the formula R.sub.4,
R.sub.5--Si--O where the aryl substituents (R.sub.4 and R.sub.5
groups) can be phenyl groups, mono- lower alkyl substituted phenyl
groups, or di- lower alkyl substituted phenyl groups, and can be
identical with one another or different from one another.
Preferably, both aryl groups are simple phenyl, and the resulting
diphenyl siloxane unit is present in the copolymer in a ratio of
approximately 14 to 16 mol per cent. In the hereinafter described
specific example, the diphenyl siloxane unit content of the
copolymer is approximately 15 mol per cent.
[0016] It is noted in connection with the diaryl, preferably simple
diphenyl substituted siloxane units, that the presence of the aryl
groups tends to increase the optical refractive index of the
copolymer.
[0017] The copolymer is end blocked with trisubstituted
(monofunctional) siloxane units, an important feature of which is
that at least one substituent of the end blocking group contains an
olefenic bond. Thus, the general formula of the end blocking group
incorporated in the copolymer of the invention in
R.sub.1,R.sub.2,R.sub.3--Si--O where the nature of the R.sub.1 and
R.sub.2 is not critical, and they may be, for example, alkyl, aryl,
or substituted alkyl or substituted aryl groups. R.sub.1 and
R.sub.2 may be identical to one another, and may also be different
from one another. The nature of the R.sub.3 group is important in
that R.sub.3 contains an olefenic bond. Thus, R.sub.3 is an alkenyl
group, preferably a vinyl group. In the preferred embodiment of the
invention the end blocking group is a dimethyl, vinyl siloxane
unit. The role of the olefenic (vinyl) group, is to enable curing
or cross-linking of the polymer an well as covalently linking, in
accordance with another feature, certain ultraviolet light
absorbing compounds to the cross-linked copolymer matrix of an
intraocular lens made in accordance with the invention.
[0018] The balance of the siloxane building blocks of the copolymer
are dialkyl siloxane units wherein the two alkyl substituents are
either ethyl or methyl. In other words, the general formula of the
balance of the siloxane building blocks of the copolymer is
R.sub.6,R.sub.7--Si--O where the R.sub.6 and R.sub.7 groups are
methyl or ethyl and the two groups are either identical with one
another, or are different from one another. Preferably in the
practice of the present invention both R.sub.6 and R.sub.7 groups
are methyl.
[0019] In accordance with the present invention the copolymer
having the above-described components has a degree of
polymerization (dp) of approximately 100 to 2000, although a degree
of polymerization of approximately 250 is preferred particularly
when the R.sub.4 and R.sub.5 groups are phenyl and the R.sub.6 and
R.sub.7 groups are methyl.
[0020] Except to the extent that novel features are emphasized
below, the preparation of the copolymer having the above described
components can be performed in accordance with processes known in
the art, from starting materials which are either commercially
available or can be made in accordance with well known
state-of-the-art processes.
[0021] Thus, in accordance with standard practice in the art,
readily available cyclic oligomers of the components and suitable
state-of-the-art precursors of the end blocking groups are reacted
in the presence of a suitable catalyst to achieve polymerization to
the desired degree. The cyclic oligomer starting materials are beat
exemplified by reference to the specific example of the moat
preferred embodiment of the copolymer of the invention.
Specifically, a mixture of octophenylcyclo-tetrasiloxane,
octanethylcyclo-tetrasiloxane and 1,2 divinyltetramethyldisiloxane
are reacted in the presence of a polymerization catalyst to achieve
a degree of polymerization which is approximately 250 for the
preferred embodiment.
[0022] It should be specifically understood in connection with the
preparation of the copolymer that after the proper copolymer
composition is selected, the selection of suitable starting
materials for the polymerization is within the skill of the
ordinary artisan. Similarly, the polymerization can be conducted by
using state of the art catalyst; the well known N-catalysts and
K-catalysts are particularly of choice in this regard. As is known
in the art, the K-catalysts used for polysiloxane formation
comprise potassium hydroxide, whereas the N-catalysts comprise
tetromethylammonium hydroxide.
[0023] It is an important aspect of the process for preparing the
copolymer of the present invention that the degree of
polymerization is monitored by monitoring the viscosity of the
reaction mixture. Moreover, the optical refractive index of the
reaction mixture is also monitored, and the reaction is not
considered completed, nor giving acceptable product unless the
reaction mixture has a viscosity within a desired range and an
optical refractive index of at least 1.44. The desired viscosity
range depends on the nature and composition of the copolymer; for
the preferred copolymer having dimethylvinylailoxane end blockers,
approximately 15 mol per cent diphenyl siloxane building blocks
with the balance being dimethylsiloxane, and a degree of
polymerization of approximately 250, the desired viscosity range of
the reaction product is approximately 2000 to 2800 centipoise (cp).
In this connection it is noted that whereas the aryl content of the
copolymer greatly influences the refractive index, the degree of
polymerization does not. The degree of polymerization, on the other
hand, greatly influences the viscosity of the polymer.
[0024] After the desired level of polymerization and refractive
index is achieved, the catalyst is inactivated, neutralized, or
removed and the reaction product is carefully filtered, for example
on a filter press, to remove any unreacted solid starting materials
or other solid impurities.
[0025] After filtration, volatile materials are carefully removed
from the copolymer by repeated exposure to vacuum, preferably while
the copolymer is in a thin film form. The careful removal of
volatiles, commonly termed "stripping", is consired important for
the purpose of obtaining material suitable for use as intraocular
lens. The "stripping" is preferably conducted in a state-of-the-art
"wipe film evaporator" using large "wipe films" and the process is
monitored by gas column chromatography of the removed volatiles. As
it will be readily appreciated by those skilled in the art, the
removed "volatiles" are residues of starting materials, cyclic and
linear oligosiloxanes and the like.
[0026] Moreover, because in virtually every polymerization the
molecular weight, or degree of polymerization of the resulting
polymeric products follow a substantially bell shaped curve, the
crude reaction product copolymer of the present invention also
contains products having substantially lesser degree of
polymerization, than for example the desired dp of 250 for the
preferred embodiment. In this regard it should be understood that a
dp of 250 of the preferred embodiment is to be construed as such dp
numbers are normally construed in the art of polysiloxane
chemistry. A dp of 250 thus means that the average dp of the
polymeric product is approximately 250 .
[0027] Stripping of the copolymeric product is repeated several
times, preferably three times. This process removes a significant
amount of the lower dp copolymers; usually approximately 12 percent
by weight of the reaction product is removed by "stripping".
[0028] It is considered important in the practice of the present
invention to monitor viscosity and refractive index at the end of
the process of removing volatiles. The refractive index of the
copolymer should be at least 1.44. As it was noted above, the
desired viscosity depends on the precise nature of the copolymer,
for the preferred embodiment the viscosity of the "stripped"
copolymer should be approximately 4100 to 5300 cp.
[0029] The elastomeric composition of the present invention
contains a trimethylsilyl treated silica reinforcer finely
dispersed in the copolymer. Blending trimethylsilyl treated "fume
silica" into a polysiloxane copolymer for the purpose of improving
the mechanical porperties of the resulting composition per se, is
not new in the art. Nevertheless, the composition of the present
invention is considered novel and highly unobvious because of the
hitherto unattained highly desirable optical and mechanical
properties of the reinforced composition.
[0030] In accordance with the invention, the fume silica reinforcer
is used in a ratio of approximately 15 to 45 parts by weight of the
reinforcer to 100 parts of the copolymer. Fume silica itself is
commercially available. Processes for trimethylsilylating the
surface of fume silica for the purpose of rendering the silica
surface hydrophobic and compatible with polysiloxane polymers are
also known and within the skill of the ordinary artisan. U.S. Pat.
Nos. 3,341,490 and particularly 3,036,985 refer to and describe
such processes for trimethylsilylating fume silica, and the
specifications of these two patents are expressly incorporated
herein by reference.
[0031] In accordance with the present invention the fume silica
reinforcer used for the composition has a surface area of
approximately 100 to 450 meter.sup.2/gram. For the preferred
embodiment of the composition the fume silica has a surface area of
approximately 200 meter.sup.2/gram, is present in a weight ratio of
approximately 27 parts to 100 parts of the copolymer, and is
preferably trimethylsilylated with hexamethyldisilazone
substantially in the same step where the copolymer is intimately
mixed with the silica. The intimate mixing is preferably aided by
treating the mixture on a roll mill or like device. After intimate
mixing, volatiles, such as unreacted silylating agent, gaseous
by-products and water are removed from the mixture by heat and
vacuum.
[0032] The intimate mixture of the trimethylsilylated fume silica
with the copolymer is commonly termed "base" in the art. For the
purpose of making materials suitable for intraocular lens, the base
is dispersed in a suitable inert solvent, such as
trichlorotrifluoroethene (FREON) and the dispersion is filtered to
remove any solid impurities. Thereafter, the solvent is removed by
gentle heat and vacuum.
[0033] The resulting, volatile free uncured (not yet cross-linked)
and optically clear reinforced silicone elastomer base, has in
accordance with the present invention, an optical refractive index
of at least 1.44 and a viscosity in such a range which permits
intimate mixing of the base with suitable catalyst and cross
linking agents, and subsequent manipulation for forming, preferably
by molding, into intraocular lenses. The acceptable viscosity range
for this purpose is approximately 35,000 to 80,000 cp. For the
preferred embodiment of the invention, the refractive index of the
uncured base is approximately 1.462.+-.0.003 and the viscosity is
in the range of 35,000 to 70,000 cp.
[0034] It is an important feature of the present invention that the
uncured base has the inherent characteristics of providing, after
suitable curing by cross-linking, physical properties which are
highly advantageous for a soft intraocular lens. Thus, after the
hereinafter described curing or cross-linking steps, the properties
of the resulting cross-linked elastomer include in accordance with
the present invention the following:
[0035] an optical refractive index which is at least 1.44;
[0036] a Shore A durometer hardness value of at least 35;
[0037] a tensile strength of at least 500 psi;
[0038] a 150 percent minimum elongation (without damage), and
[0039] a tear strength of at least 20 pounds per lineal inch
(pli).
[0040] The above listed properties can be measured in accordance
with state-of-the-art technology and instruments in accordance with
the respective requirements of standard ASTM test methods. More
particularly, the durometer test is performed as ASTM D2240, the
tensile and elongation tests as ASTM D412 and the tear strength
test as ASTM D624 Die B.
[0041] Preferably, the optical refractive index of the cross linked
elastomer obtainable from the base is approximately 1.462, the
durometer hardness is approximately between 38 to 40, the tensile
strength is approximately between 700 to 750 psi, and the tear
strength is approximately 40 pli. In this regard it is noted that
cross-linking tends to slightly increase the optical refractive
index as compared to the uncured base.
[0042] Preparation of the uncured base for cross-linking is
accomplished as follows. The base is filtered once more, preferably
through a 325 mesh screen to remove any remaining solid impurities.
Thereafter, in accordance with standard practice in the art, the
base is divided into two aliquots which preferably are of equal
weight. The aliquots are commonly termed "Part A" and "Part B", or
first and second aliquot parts.
[0043] As is known in the art, cross-linking is accomplished by
utilizing in a platinum catalyzed reaction the terminal silicon
bonded olefinic (vinyl) groups of the base, and silicon bonded
hydrogen groups. The silicon bonded olefinic (vinyl) groups are
present both in the first and second aliquots of the base.
[0044] Silicon bonded hydrogen groups are added in the practice of
the present invention to the second aliquot (Part B) in the form of
suitable cross-linking agents. The cross-linking agents per se are
known in the art, and may be made in accordance with the teachings
of U.S. Pat. No. 3,436,366 the specification of which is
incorporated herein by reference.
[0045] Whereas a number of cross-linking agents are suitable for
the practice of the invention and can be selected by those skilled
in the art, the liquid organohydrogen polysiloxane cross linkers
shown in column 2 of the above-noted U.S. Pat. No. 3,436,366 and
having the formula (R).sub.a(H).sub.bSiO.sub.4-a-b/2 wherein R is
simple lower alkyl and a ranges from 1.00 to 2.10 and b ranges from
0.1 to 1.0, are eminently suitable. Particularly suitable is the
liquid organohydrogen polysiloxane cross-linker of the
above-referenced U.S. Pat. No. 3,436,366 having the formula
R.sub.2HSiO.sub.1/2, and the liquid cross linker described in
Column 4 lines 3-14 of said patent reference wherein the R groups
are primarily or predominantly methyl.
[0046] The platinum catalyst can also be selected within the skill
of the ordinary artisan, primarily from organo platinum compounds,
for example in accordance with the specifications of U.S. Pat. Nos.
2,823,218 and 3,159,601, which are expressly incorporated herein by
reference. The platinum catalyst is added to the first aliquot
(Part A).
[0047] It is important in accordance with the invention that after
mixing of the aliquots (Parts A and Parts B), the cross-linking
should not proceed too rapidly at room temperature, thereby
allowing at least two, preferably approximately six hours for work
time with the mixed aliquots. For this reason, a suitable
cross-linking inhibitor, such as 1,2,3,4
tetramethyl-1,2,3,4-tetramethyl cyclotetrasiloxane, is also added
to the second aliqout (Part B).
[0048] Although the precise amounts can be adjusted within the
skill of ordinary artisan, the organo platinum catalyst is added to
the first aliquot in 12 part per million (12 ppm) by weight. The
cross-linker is added to the second aliquot in the range of
approximately 1 to 6 parts per hundred (1-6 pph) by weight. The
above specified inhibitor is also added to the second aliquot in
the range of 0.01 to 0.2 parts per hundred by weight.
[0049] It has been found in accordance with the present invention
that best results, in terms of desired curing times, are obtained
when the amount of inhibitor used in the second aliquot is adjusted
on small samples of each batch. The adjustment within the
above-noted ranges serves to provide approximately 6 hours of work
time at room temperature. In other words, the material should not
cure significantly at room temperature within six hours. Before
curing or cross-linking, the first and second aliquots are
intimately mixed, preferably in equal amounts.
[0050] In addition to the above-described cross-linker and
inhibitor, an ultraviolet ray absorbing material is also optionally
mixed into the second aliquot in accordance with the teachings of
co-pending application for U.S. patent Ser. No. 946,703 filed on
Dec. 24, 1986 by Reich et, al, and titled ULTRAVIOLET LIGHT
ABSORBING SILICONE COMPOSITIONS.
[0051] The ultraviolet ray absorbing material, which in accordance
with teachings of the above-noted patent application is a vinyl
functional 2-hydroxybenzophenone, or a vinyl functional
benzotriazole is covalently linked to the copolymer of the
composition during the cross linking step. Preferably, the
ultraviolet absorbing material is 2(2'-hydroxy-3'-t-butyl-
-5'-vinyl-phenyl)-5-chloro-2H-benzotriazole, and is added in an
amount of approximately 0.5 weight percent to the second aliquot,
Consequently, in the final cured elastomer, the above-named u. v.
absorbent is present in approximately 0.25 per cent (by
weight).
[0052] Although the chemical reactions involved in the crosslinking
are well known in the art, they are summarized here for the sake of
completeness an involving the formation of ethylenic
(CH.sub.2--CH.sub.2) bridges linking one copolymer chain to a
polysiloxane cross linking molecule. The polysiloxane cross linker
molecule, in turn, is again linked through an ethylenic bridge to a
second copolymer chain. In essence, the chemical reaction involves
saturation of a vinyl (or other unsaturated) groups of an end
blocker with the hydrogen derived from an at least difunctional
organohydrogen polysiloxane and formation of a carbon to silicon
bond. This reaction is catalyzed by the platinum catalyst.
[0053] The vinyl functional u. v. absorbant reacts with the
organohydrogen polysiloxane cross-linking agent in essentially the
same way as the vinyl group of the copolymer, and forms a carbon to
silicone bond which covalently links the u. v. absorber to the
copolymer network.
[0054] Formation of intraocular lens bodies from the elastomeric
compositions of the present invention may be accomplished by liquid
injection molding or by coat or compression molding of the
intimately mixed first and second aliquots. Although these
processes are well known in the art, they are briefly summarized by
description of the following examples.
[0055] In the liquid injection molding process the mixed aliquots
are injected into a hot mold kept at approximately 120 to 150 C.
The cross-linking or curing process is then complete in
approximately five minutes.
[0056] In the cast or compression molding process, the mixed
aliquots are placed into appropriate molds, and the molds are
thereafter positioned in an oven heated to approximately 150 C.
Under these conditions the cure is complete in approximately 15 to
30 minutes. The cast molding process can also be completed at room
temperature in significantly longer time periods.
[0057] The intraocular lenses made in accordance with the present
invention have the above-described advantagous optical and
Mechanical properties. The unusually high optical refractive index
of 1.44 or greater, permits the fabrication of lenses which are at
their apex only approximately 1.1 to 1.15 mm thick. This is a
significant advance over prior art intraocular lenses which, being
made of materials having lower refractive indices, at typically are
1.42 mm thick at their apex.
[0058] An additional advantage of the intraocular lenses made in
accordance with the invention is that they do not absorb energy at
1064 nm, thereby permitting follow-up LASER surgery in the eye
after implantation of the lens.
[0059] Several modifications of the invention may become readily
apparent to those skilled in the art in light of the foregoing
disclosure. Therefore the scope of the present invention should be
interpreted solely from the following claims. Further particulars
of the preferred embodiment of the invention are described in the
following description of an example of making the elastomeric
compositions of the invention.
SPECIFIC EXAMPLE
[0060] Preparation of Crude Copolymer
[0061] In a 50 gallon reactor (Baker Perkins) mix
octaphenylcyclotetrasilo- xone (phenyl cyclics) (44.550 kg),
octaphenylcyclotetrasiloxone (dimethylcyclics) (93.462 kg) and
1,2-divinyltetramethyldisiloxane (1.116 kg) and heat under
agitation and a nitrogen gas blanket to 100 C. When the temperature
reaches 100 C add 0.18 per cent (by weight) N-catalyst (about 250
g). Continue heating and stirring and monitor viscosity of samples
taken from the reaction mixture. If after 45 minutes there is no
change in viscosity, add 0.18 per cent more N-Catalyst (about 75
g). After viscosity change has been observed and the phenyl cyclics
have dissolved continue heating and stirring for 3 hours. Then
neutralize or destroy the catalyst, for example by bubbling
CO.sub.2 into the mixture, or heating to 150 C. Viscosity of the
cooled reaction mixture should be between 2000 to 2800 cp, the
refractive index should be between 1.459 to 1.465.
[0062] Purification of Copolymer
[0063] Filter the cooled reaction mixture on a filter press with a
pressure of about 40 psi on five or more filter plates using Zeta
Plus filter paper, catalog # A1311-10A. Strip the filtered
copolymer at least three times on a "wipe film evaporator". Monitor
the process of stripping by gc, taking samples of 1 g of the
volatiles and dissolving the same in 3 g of hexene. Continue
stripping until gc indicates adequate devolatilization. Viscosity
of stripped copolymer should be between 4100 to 5300 cp, the
refractive index should be between 1.459 to 1.465.
[0064] Formulation of Base Including Silica Reinforcer
[0065] In a 50 gallon mixer mix the stripped polymer (75 kg) with
hexamethyldisilazane (3.6. kg). Add MS-7 silica (30 kg, surface
area 200 m.sup.2/g) in increments, and with last silica load add
distilled water (1.2 kg), mix well. Thereafter mill mixture twice
on three roll mill, and return mixture to 50 gallon mixer. Heat
mixer to reach internal temperature of 150 to 200 C. After 30
minutes of heating and stirring at above temperature, apply vacuum
and continue heating for 2.5 hours while the mixer reactor is under
vacuum. Cool mixture under vacuum. After cooling add more stripped
polymer (36.11 kg) as a "cut-back" and mix well. Let a small sample
of base settle (unstirred) for about 30 minutes and check viscosity
at 25 C. of with Brookfield viscometer, viscosity should be between
35,000 to 70,000 cp.
[0066] Purification of Base
[0067] Disperse the base in trichlorotrifluoroethane (FREON) in a
ratio of about 2 gallons of base to 1 gallon of FREON, and add
about 0.5 gallon of dictomaceous earth to the dispersion for each 2
gallons of base. Filter the dispersion on a filter press using Zeta
Plus filter paper, catalog # A1311-10A. Pressure during filtration
should be kept at about 30 psi and should not exceed that value.
Clear filrate is required. Place the collected clear filtrate in a
reactor, and agitate under nitrogen purge. Apply vacuum gradually
while purging slowly with nitrogen. Heat slowly to 110 C. and
continue heating under vacuum. Take samples for weight loss test.
Continue heating under vacuum until weight loss on samples taken
indicates no more than 0.5 per cent loss. Thereafter cool to obtain
stripped base.
[0068] Preparation of Aliquots (Parts A and B) Ready for
Cross-Linking.
[0069] Screen stripped base through 325 mesh steel wire screen
under pressure. Divide the batch into two equal parts, Part A and
Part B. Mix into Part A the organoplatinum catalyst to provide 12
parts per million by weight. Take small samples from Part B and mix
in the cross-linker (liquid organohydrogen polysiloxone having the
structure R.sub.2HSiO.sub.1/2with the R groups being predominantly
methyl). Optimize the cross linker level, so as to obtain a Shore
durometer hardness of approximately 35 (ASTM D2240) in the
cross-linked product, Thereafter, gradually add increasing amounts
of the inhibitor (1,2,3,4 tetramethyl-1,2,3,4-tetravinyl
cyclotetrasiloxane) to Part B and test mixed samples of Parts A and
B to obtain a working time of about 6 hours at room temperature.
Depending on the above-noted sample teat results, the cross linker
is added to Part B to provide 1-6 parts per hundred by weight, and
the inhibitor is added to Part B to provide 0.01 to 0.2 parts per
hundred by weight.
[0070] Optionally, intimately mix in the u. v. light absorbent
2(2'-hydroxy-3'-t-butyl-5'-vinyl-phenyl)-5-chloro-2H-benzotriazole
in an amount which corresponds to approximately 0.5 per cent by
weight in Part B.
[0071] Screen Part A and Part B separately from one another on 325
mesh screen to remove any solid contaminants. For cross-linking or
curing to obtain intraocular lenses proceed in accordance with
procedures required for liquid infection molding, or cast
molding.
1 APPENDIX A DOCKET NO. PATENT # 14101 3,873,696 14104CIP 4,029,817
14106 4,127,674 14108CIP-2 4,395,346 14109 4,230,724 14111
4,244,948 14144 3,888,782 14145 3,822,780 14146 3,954,965 14147
3,966,924 14149 4,197,301 14150 4,255,419 14152 3,749,776 14153
3,733,178 14167 D279,357 14192 4,524,063 14204 4,743,588 16502
4,670,178 16502Reissue RE32,672 16505 4,786,651 16518 4,725,620
16519 4,739,098 16534CIP-1 4,763,651 16540DIV-1 4,786,445 16542FWC
4,759,761 16543 4,704,122 16544 4,834,751 16544DIV1 4,894,062
16544RE-DIV RE34,448 16546 4,790,846 16546DIV-1 4,888,013
16546DIV-2 4,880,426 16546DIV-3 4,938,767 16546DIV-4-CIP-1
5,133,746 16546DIV-4 4,978,354 16546DIV-4-CON-1 5,171,268 16547
4,684,014 16548FWC 4,838,682 16549 4,842,782 16549-CIP-2 5,053,171
16549-CIP-2-DIV1 5,179,262 16549DIV-FWC 5,061,840 16550 4,932,970
16552 4,576,798 16553DIV-1 4,927,947 16553DIV-2 4,980,484 16553FWC
4,923,884 16554 4,597,649 16556FWC-2 5,236,970 16556-FWC-2-DIV-1
5,376,694 16557DIV-1 4,983,580 16557DIV-2 4,981,841 16559CIP
4,868,251 16560 5,149,705 16560DIV 5,246,962 16560DIV-2 5,354,776
16560DIV-3 5,466,690 16561CIP-1 5,089,509 16561CIP-2 5,264,578
16561CIP-DIV 5,234,926 16561CIP-DIV-4 5,380,877 16561CIP-DIV-3
5,348,972 16561DIV-CIP-2 5,468,879 16561CON-DIV-2-CIP 5,354,752
16562 4,810,804 16564CIP&16653CIP 5,134,128 16568 4,759,359
16569 4,834,748 16571 4,817,789 16571DIV 4,928,815 16575 4,208,365
16578 4,452,925 16578REISSUE RE33,997 16580 4,388,428 16582
5,030,231 16582DIV-1 5,088,809 16582CIP-DIV-1 5,196,028 16584
4,517,138 16588 4,551,086 16590 4,468,184 16591 4,647,261 16592
4,681,295 16594DIV-1 4,584,148 16594 4,534,723 16597 4,492,854
16607 DE256,049 16608 DE256,391 16609 DE256,392 16610 DE257,174
16611 DE257,486 16612 DE257,789 16613 DE264,377 16614 DE267,652
16615 DE276,367 16616 3,925,825 16617 3,996,627 16618 3,975,779
16619 3,971,073 16620CIP-1 3,996,626 16620 4,150,471 16621
4,012,823 16622 4,015,965 16623 4,028,082 16624DIV-1 4,071,343
16624 4,025,965 16625 4,014,049 16626 4,139,915 16628 4,079,470
16632 4,838,413 16636 4,845,180 16638FWC-2 5,192,316 16639CON-DIV-1
5,231,113 16639CONT 5,130,335 16640 4,895,868 16640CIP 5,015,658
16642 4,897,079 16643 4,842,602 16643DIV-1 4,888,014 16644FWC
5,300,262 16644 5,076,683 16645 4,935,530 16646 4,860,885
16647CIP-1 5,089,485 16648CIP-1 5,059,611 16649CIP-1 4,957,917
16651CIP 5,424,078 16652CIP-1 5,045,564 16652CIP-2 5,376,676
16654FWC-2-CIP 5,399,573 16655 5,044,743 16657DIV-1 4,328,148
16657DIV-2 4,465,794 16657 4,275,183 16660 4,469,646 16661
4,517,140 16662 4,516,924 16663 4,645,811 16664 4,568,501 16665
4,534,916 16669 4,445,362 16670 4,583,830 16680 4,438,100
16687FWC-DIV-2 5,166,711 16687FWC-DIV-1-CIP 5,225,858
16687FWC-DIV-3 5,270,744 16693 3,739,455 16694 3,829,536 16695
3,827,798 16697 3,751,138 16715 4,983,901 16740 DE315,164 16744-CIP
5,180,721 16744DIV-CIP 5,281,591 16748 4,889,421 16752 5,310,571
16752DIV 5,475,450 16753 4,666,446 16754 5,078,908 16754DIV-2
5,306,440 16754DIV-FWC 5,246,662 16755FWC 5,028,624 16756FWC
5,446,041 16757 4,992,468 16757DIV-1 5,068,252 16758FWC 5,034,413
16760 5,034,406 16761CIP-1 5,112,822 16761CIP-2 5,231,096
16761CIP-2-DIV 5,326,763 16761CIP-2-DIV-2 5,373,010
16761CIP-2-DIV-3 5,418,234 16761DIV-1 5,204,347 16761DIV-2
5,300,504 16761DIV-CIP 5,198,442 16761 5,077,292 16763 5,093.329
16764 5,045,551 16764DIV 5,183,827 16764DIV-2 5,272,156 16764DIV-3
5,407,937 16765 4,980,369 16765CIP-DIV 5,162,546 16765CIP-DIV-2
5,278,318 16766 5,023,341 16766DIV 5,053,523 16766DIV-3 5,248,777
16767 5,279,673 16767DIV-1 5,152,912 16768CIP 5,262,097
16768CIP-DIV 5,344,449 16768 5,147,397 16769CIP 5,135,623 16769
4,997,626 16769DIV 5,320,806 16771 5,171,526 16772 5,145,643
16772CIP 5,277,901 16772CIP-2 5,451,398 16773 4,955,889 16774
5,098,439 16774DIV-FWC 5,222,972 16775DIV 5,194,449 16775 5,011,856
16777CON-DIV 5,258,400 16777CON 5,112,853 16778 5,019,097 16779
5,021,416 16784CON 5,198,545 16784 5,055,467 16785DIV-2-CIP
5,453,434 16785 5,264,449 16786 4,615,702 16787 4,702,865 16788
4,878,910 16796 5,013,744 16796DIV 5,175,185 16796DIV-2 5,264,456
16796DIV-3 5,414,007 16797 5,006,550 16798CIP 5,215,991 16800
4,757,089 16801 5,130,441 16801DIV 5,237,072 16802 5,129,999 16804
5,281,353 16804DIV-1 5,330,752 16805DIV-1 5,312,588 16807 5,111,029
16808 5,202,471 16808CON 5,349,105 16809 5,066,664 16812 5,151,440
16812DIV 5,252,595 16813CIP 5,441,732 16813 5,252,318 16814
5,081,147 16814DIV 5,212,172 16815 5,081,261 16816CIP 5,376,737
16816CIP-2 5,352,753 16816CIP-2-DIV 5,466,768 16816CIP-3 5,397,848
16816 5,164,462 16818CIP 5,395,621 16818FWC 5,362,444 16819
5,013,850 16820CIP 5,474,780 16822 5,238,961 16823 5,037,811 16824
5,043,457 16826 5,173,298 16827 5,100,431 16829 5,139,491 16831
5,323,775 16834 5,296,228 16835 5,275,820 16836 5,276,044 16838
5,091,528 16841 5,270,049 16845 5,183,906 16846 5,225,571 16847
5,169,963 16848 5,171,864 16851CIP 5,262,437 16854 5,312,832 16855
5,288,754 16856CON 5,346,915 16857CON 5,270,002 16860 5,145,644
16864CIP 5,082,954 16864DIV 5,171,863 16864DIV-2 5,322,953
16864DIV-3 5,298,633 16868 5,292,517 16870 5,356,555 16871
5,143,104 16872FWC 5,209,783 16873 5,455,265 16877 5,134,159
16877DIV 5,324,744 16877DIV-2 5,348,975 16878CIP 5,338,480
16878CIP-2 5,324,447 16878CIP-3 5,336,434 16879CON 5,346,895 16881
5,391,590 16883CIP 5,242,449 16883DIV-CIP 5,364,405 16884 5,147,395
16885 5,152,789 16891 5,197,636 16892FWC 5,401,508 16898 5,197,638
16899 5,252,246 16902 5,213,760 16903 5,249,002 16905CIP 5,392,653
16906CIP 5,470,312 16907 5,230,614 16908 5,224,593 16913CIP
5,303,023 16916DIV 5,411,553 16916 5,278,258 16921 5,233,007
16921FWC-DIV 5,420,213 16925 5,462,968 16926 5,326,898 16927CON
5,391,753 16927DIV 5,434,173 16928 5,201,763 16932CIP 5,422,073
16936 5,420,295 16937 5,268,387 16937DIV 5,387,606 16940 5,260,021
16941 5,340,583 16942FWC 5,387,394 16943DIV 5,300,114 16943
5,178,635 16945 5,324,840 16945CIP 5,475,113 16946 5,281,227 16948
5,268,624 16949 5,384,606 16950 5,320,256 16950DIV 5,427,274 16951
5,385,945 16953 5,300,499 16954FWC 5,324,180 16955 5,352,708 16956
5,332,730 16957 5,312,842 16959 5,468,778 16960 5,328,933 16961
5,284,472 16963 5,375,698 16965 5,389,383 16967 5,331,073
16967DIV-1 5,359,021 16971 5,344,959 16972 5,426,118 16973
5,451,605 16974 5,470,999 16977 5,399,561 16982 5,451,686 16983
5,362,647 16984 5,342,293 16985 5,387,180 16988 5,399,586 16990
5,416,106 16991 5,369,127 16992 5,387,608 16992DIV 5,457,131
16995CIP 4,568,517 17000 5,358,473 17003 5,382,599 17005 5,447,650
17010 5,433,745 17012 5,451,237 17013 5,423,929 17018 5,476,872
17022 5,419,775 17024 4,664,667 17025 5,474,979 17042 5,443,178
17050 5,084,012 17051 5,217,465 17104 4,608,049 17117 4,681,102
17162 4,900,366 17164 5,238,153 17167 4,826,001
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