U.S. patent application number 13/449412 was filed with the patent office on 2012-11-08 for macroinitiator containing hydrophobic segment.
Invention is credited to Kazuhiko Fujisawa, Masataka Nakamura, Ryuta Tamiya.
Application Number | 20120283381 13/449412 |
Document ID | / |
Family ID | 47090656 |
Filed Date | 2012-11-08 |
United States Patent
Application |
20120283381 |
Kind Code |
A1 |
Tamiya; Ryuta ; et
al. |
November 8, 2012 |
MACROINITIATOR CONTAINING HYDROPHOBIC SEGMENT
Abstract
The present invention relates to macroinitiators comprising at
least one hydrophobic segments in a molecule, wherein a molecular
weight of the hydrophobic segment is 300 to 1800. The present
invention further relates to block copolymers, wetting agent and
polymeric materials having the block copolymers of the present
invention associated with, which is suitable for medical devices,
particularly for ophthalmic devices, including contact lenses,
ophthalmic lenses, punctal plugs and artificial corneas.
Inventors: |
Tamiya; Ryuta; (Shiga,
JP) ; Fujisawa; Kazuhiko; (Shiga, JP) ;
Nakamura; Masataka; (Shiga, JP) |
Family ID: |
47090656 |
Appl. No.: |
13/449412 |
Filed: |
April 18, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61482260 |
May 4, 2011 |
|
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Current U.S.
Class: |
524/588 ;
525/418; 528/26 |
Current CPC
Class: |
C08L 2201/10 20130101;
C08G 77/452 20130101; C08L 2201/54 20130101; G02B 1/043 20130101;
C08L 83/10 20130101; G02B 1/043 20130101; G02B 1/18 20150115; A61L
12/14 20130101; A61L 27/18 20130101; C08L 2203/02 20130101; C08G
77/26 20130101; C08L 101/14 20130101; C08L 83/04 20130101; A61L
27/18 20130101; C08L 83/08 20130101; C08L 83/04 20130101; A61L
2430/16 20130101; G02B 1/043 20130101; C08G 77/388 20130101 |
Class at
Publication: |
524/588 ; 528/26;
525/418 |
International
Class: |
C08L 83/08 20060101
C08L083/08; C08G 77/455 20060101 C08G077/455; C08G 77/26 20060101
C08G077/26 |
Claims
1. A macro initiator comprising one or two hydrophobic segments in
a molecule, wherein a molecular weight of the hydrophobic segments
is 300 to 1800.
2. The macro initiator according to claim 1, wherein the
hydrophobic segment is a segment made from polysiloxane.
3. The macro initiator according to claim 2, expressed by formula
(a0) or (a1). Formula: ##STR00010## (wherein in (a0) and (a1),
R.sup.1 is one type of group selected from an alkyl group or an
alkoxy group; R.sup.2 is one type of group selected from
(CH.sub.2).sub.n and (CH.sub.2).sub.m--O(CH.sub.2).sub.n; m and n
are independent, ranging from 1 to 16; a is from 4 to 19; b is from
1 to 6, and X is one type of group selected from O, NH, and S).
4. A block copolymer comprising one hydrophobic segment and one
hydrophilic segment, wherein a molecular weight of the hydrophobic
segment is 300 to 1800.
5. The block copolymer according to claim 4, wherein the
hydrophobic segment is a segment made from polysiloxane.
6. The block copolymer according to claim 5, expressed by formula
(b1). Formula: ##STR00011## (wherein in (b1), R.sup.1 is one type
of group selected from an alkyl group or an alkoxy group; R.sup.2
is one type of group selected from (CH.sub.2).sub.n and
(CH.sub.2).sub.m--O(CH.sub.2).sub.n; m and n are independent,
ranging from 1 to 16; a is from 4 to 19; b is from 1 to 6, c is
from 1 to 10,000, X is one type of group selected from O, NH, and
S; and R.sup.3 and R.sup.4 represent groups made of monomers with
hydrophilicity wherein a monomer is expressed by general formula
(n)). ##STR00012##
7. The block copolymer according to any one of claims 1 through 6,
wherein a weight-average molecular weight is from approximately
10,000 to approximately 3,000,000.
8. The block copolymer according to any one of claims 4 through 7,
further comprising approximately 0.01 to approximately 5 weight %
of a hydrophobic segment and approximately 95 to approximately 99.9
weight % of a hydrophilic segment.
9. The block copolymer according to any one of claims 4 through 8,
wherein the hydrophilic segment is made from a hydrophilic polymer
selected from a group consisting of poly-N-vinyl-2-pyrrolidone,
poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactum,
poly-N-vinyl-3-methyl-2-caprolactum,
poly-N-vinyl-3-methyl-2-piperidone,
poly-N-vinyl-4-methyl-2-piperidone,
poly-N-vinyl-4-methyl-2-caprolactum,
poly-N-vinyl-3-ethyl-2-pyrrolidone,
poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinyl imidazole,
poly-N--N-dimethyl acrylamide, poly-N-vinyl-N-methyl acetamide,
polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, and
poly(hydroxyethyl methacrylate), as well as blends and copolymers
thereof.
10. A medical material comprising a block copolymer according to
any one of claims 4 through 9.
11. A manufacturing method for a block copolymer according to any
one of claims 4 through 9, wherein a monomer that can form a
hydrophilic segment is polymerized using a macro initiator
according to any one of claims 1 through 3.
12. A contact lens wetting agent, comprising a block copolymer
containing one or more hydrophobic segments and one or more
hydrophilic segments, wherein a molecular weight of the hydrophobic
segment is 300 to 1800.
13. The contact lens wetting agent according to claim 12, wherein
the block copolymer is a block copolymer expressed by formula (b1)
or (b2) below. ##STR00013## (wherein in (b1) and (b2), R.sup.1 is
one type of group selected from an alkyl group or an alkoxy group;
R.sup.2 is selected from the group consisting of (CH.sub.2).sub.n
or (CH.sub.2).sub.m--O(CH.sub.2).sub.n; m and n are independent,
ranging from 1 to 16; a is from 4 to 19; b is from 1 to 6, c is
from 1 to 10,000, X is one type of group selected from O, NH, and
S; and R.sup.3 and R.sup.4 represent groups made of monomers with
hydrophilicity wherein a monomer is expressed by general formula
(n)). ##STR00014##
14. The contact lens wetting agent according to claim 12 or 13,
wherein a weight-average molecular weight of the block copolymer is
from approximately 10,000 to approximately 3,000,000.
15. The contact lens wetting agent according to any one of claims
12 through 14, wherein the block copolymer contains approximately
0.01 to approximately 5 weight % of a hydrophobic segment and
approximately 95 to approximately 99.9 weight % of a hydrophilic
segment.
16. The contact lens wetting agent according to any one of claims
12 through 15, wherein the hydrophilic segment is a segment made
from a hydrophilic polymer selected from the group consisting of
poly-N-vinyl-2-pyrrolidone, poly-N-vinyl-2-piperidone,
poly-N-vinyl-2-caprolactum, poly-N-vinyl-3-methyl-2-caprolactum,
poly-N-vinyl-3-methyl-2-piperidone,
poly-N-vinyl-4-methyl-2-piperidone,
poly-N-vinyl-4-methyl-2-caprolactum,
poly-N-vinyl-3-ethyl-2-pyrrolidone,
poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinyl imidazole,
poly-N--N-dimethyl acrylamide, poly-N-vinyl-N-methyl acetamide,
polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, and
poly(hydroxyethyl methacrylate), as well as blends and copolymers
thereof.
17. A contact lens wetting agent solution, comprising a contact
lens wetting agent according to any one of claims 12 through
16.
18. The contact lens wetting agent solution according to claim 17,
wherein the contact lens wetting agent solution is a packaging
solution or a storage solution.
19. A medical material comprising silicone hydrogel and a block
copolymer according to any one of claims 4 through 9.
20. The medical material according to claim 19, comprising
approximately 0.1 ppm to approximately 30% of the block
copolymer.
21. The medical material according to any one of claims 18 through
20, wherein a hydrophilic monomer that is used in the silicone
hydrogel is selected from a group consisting of N,N-dimethyl
acrylamide (DMA), 2-hydroxyethyl acrylate, glycerol methacrylate,
2-hydroxyethyl methacrylate amide, polyethylene glycol mono
methacrylate, methacrylic acid, acrylic acid, N-vinyl pyrrolidone,
N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide,
N-vinyl-N-ethyl form amide, N-vinyl formamide, N-2-hydroxyethyl
vinyl carbamate, N-carboxy-beta-alanine N-vinylester, reactive
polyethylene polyol, hydrophilic vinyl carbonate, vinyl carbamate
monomer, hydrophilic oxazolone monomer, hydrophilic oxazoline
monomer, and combinations thereof.
22. The medical material according to any one of claims 18 through
21, wherein a silicone monomer that is used in the silicone
hydrogel has a hydroxyl group.
23. The medical material according to claim 22, wherein an amount
of component derived from a silicone monomer that is used in the
silicone hydrogel is approximately 5 to approximately 95 weight %.
Description
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application No. 61/482,260, filed on May 4, 2011 entitled
MACROINITIATOR CONTAINING HYDROPHOBIC SEGMENT, the contents of
which are incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to macroinitiators useful for
forming block copolymers. The present invention further relates to
block copolymers, wetting agents and polymeric materials, as well
as, medical devices incorporating the polymeric materials having
the block copolymers of the present invention.
DESCRIPTION OF THE RELATED ART
[0003] Various compounds have been disclosed as suitable for
treating preformed silicone hydrogel contact lenses including
surface active segmented block copolymers, substantially
water-soluble silicone-containing surfactants, functionalized
hybrid PDMS/polar amphipathic compolymer block systems, including
polydimethylsiloxane-PVP block copolymers and (meth)acrylated
polyvinylpyrrolidone. WO2006/039467 discloses a block copolymer
obtained by polymerizing a hydrophilic monomer using a hydrophobic
macro azoinitiator, including VPS 0501 and VPS1001 siloxane
containing macro azoinitiators of which the siloxane units have
molecular weights of 5,000 and 10,000. WO2006/039467 discloses that
the block copolymers disclosed therein may be incorporated into the
reaction mixtures and polymerized therewith to form medical devices
having improved characteristics, including wettability.
[0004] WO2008/112874 similarly discloses that a block copolymer
obtained by polymerizing a hydrophilic monomer using a hydrophobic
macro azoinitiator can be used as a lens care component for contact
lenses. No details are provided relating to the size of the macro
azoinitiator or the process for making same. No properties are
provided for the solution.
[0005] However, large polysiloxane segments can be difficult to
solubilize in aqueous solutions, such as contact lens packaging,
cleaning and care solutions. This can result in cloudy solutions
which do not impart the desired improvement in wettability to the
articles being treated. Thus there remains a need for methods for
improving the properties of contact lenses and particularly
silicone hydrogel contact lenses.
SUMMARY OF THE INVENTION
[0006] The present invention relates to macroinitiators comprising
at least one hydrophobic segment in a molecule, wherein the
molecular weight of the hydrophobic segments is 300 to 1800.
DETAILED DESCRIPTION OF THE INVENTION
[0007] As used herein "non-reactive" means incapable of forming
significant covalent bonding. The absence of significant covalent
bonding means that while a minor degree of covalent bonding may be
present, it is incidental to the retention of the block copolymer
in the polymeric article. Whatever incidental covalent bonding may
be present, it would not by itself be sufficient to maintain the
association of the non-reactive block copolymers with or in the
polymer matrix. Instead, the vastly predominating effect keeping
the block copolymers associated with the polymeric article is
entrapment of at least a portion of the hydrophobic segment. The
hydrophobic segment is "entrapped", according to this
specification, when it is physically retained within or anchored to
the polymer matrix. This is done via entanglement of the
hydrophobic segment within the polymer matrix, van der Waals
forces, dipole-dipole interactions, electrostatic attraction,
hydrogen bonding and combinations of these effects. In one
embodiment, non-reactive components are free from free radical
reactive groups.
[0008] As used herein "segment" means a residue which has a
structure comprising repeating units.
[0009] The present invention provides a block copolymer formed from
the reaction of at least one hydrophilic monomer and a macro
initiator with a hydrophobic segment having a molecular weight
between about 300 and about 1800. If the molecular weight of the
hydrophobic segment has a molecular weight distribution, the
molecular weight is weight-average molecular weight.
[0010] The macro initiator may be obtained by reacting an azo-type
initiator with a compound having the desired hydrophobic
segment.
[0011] Azo-type initiators are known in the art and include
aliphatic azo containing initiators, including one or more of the
following compounds: 4,4'-azobis(4-cyanovalearic acid) and its
derivatives,
2,2'-azobis[N-(2-carboxyethyl)-2-methylpropionamidine]hydrate,
2,2'-azobis{2-methyl-N-[2-(1-carboxybutyl)]propionamide}, and
2,2'-azobis[2-methyl-N-(2-carboxyethyl)propionamide] and the like.
In one embodiment the azo-type initiator is
4,4'-azobis(4-cyanovalearic acid).
[0012] Hydrophobic segments of the present invention are those
which do not yield a clear single phase when mixed with water at
2000 ppm at 25.degree. C. When making this measurement, each end of
the hydrophobic segment may be independently substituted with a
hydrogen atom or an initiator residue. Examples of suitable
hydrophobic segments are polysiloxanes, C.sub.8-C.sub.50 alkylene
or (poly)arylene groups, hydrophobic polymers formed from monomers
selected from the group consisting of C.sub.1-C.sub.20 alkyl or
C.sub.6-C.sub.20 aryl (meth)acrylate monomoers such as methyl
(meth)acrylate, ethyl (meth)acrylate, n-propyl (meth)acrylate,
isopropyl (meth)acrylate, n-butyl (meth)acrylate, n-decyl
(meth)acrylate, n-dodecyl (meth)acrylate, phenyl (meth)acrylate,
and naphthyl (meth)acrylate; and silicone (meth)acrylate monomers
such as 3-(meth)acryloxypropyltris(trimethylsiloxy)silane,
pentamethyldisiloxanylmethyl (meth)acrylate,
methyldi(trimethylsiloxy)(meth)acryloxymethylsilane,
mono(meth)acryloxypropy terminated mono-n-butyl terminated
polydimethylsiloxane, (2-methyl-)-2-propenoic acid,
2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disiloxanyl]pro-
poxy] propyl ester, and
9-n-butyl-1-[3-(3-(meth)acryloyloxy-2-hydroxypropoxy)propyl]-1,1,3,3,5,5,-
7,7,9,9-decamethylpentasiloxane; and vinyl or allyl silicone
monomers such as 3-[tris(trimethylsiloxy)silyl] propyl allyl
carbamate, 3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate,
trimethylsilylethyl vinyl carbonate, trimethylsilylmethyl vinyl
carbonate; and aromatic vinyl monomers such as styrene, and
vinylpyridine; and combinations thereof. In one embodiment the
hydrophobic segment of the block copolymer is a polysiloxane
segment. The polysiloxane segment may comprise C.sub.1-C.sub.4
polyalkyl and polyaryl substituted siloxane repeating units.
Examples of suitable polysiloxane repeating units include
polydimethylsiloxane, polydiethylsiloxane, polydiphenylsiloxanes
and copolymers thereof. In one embodiment the polysiloxane segment
is terminated on one end with an alkyl group, and in another
embodiment a C.sub.1-4 alkyl and in another methyl or n-butyl.
[0013] The hydrophobic segment of the block copolymer of the
present invention has affinity towards polymeric articles formed
from hydrophobic components, such as, but not limited to silicone
containing articles, such as, in one embodiment, silicone elastomer
lenses and silicone hydrogel contact lenses.
[0014] The present invention further relates to a wetting agent for
polymeric articles comprising at least partially hydrophobic
polymers, such as silicone elastomer, silicone hydrogel and PMMA
contact lenses. The block copolymers formed from the
macroinitiators of the present invention may, in one embodiment be
incorporated into packaging solutions, storage solutions and
multipurpose solutions containing the block copolymers formed via
the present invention. These solutions can provide improved
wettability to the polymeric article without performing a surface
treatment.
[0015] In one embodiment, the hydrophobic segment-containing
macroinitiators comprise one or two hydrophobic segments, each
having a molecular weight of about 300 to about 1800. In another
embodiment, the hydrophobic segment-containing macroinitiators
comprise two hydrophobic segments because block copolymers only are
obtained from the macroinitiators, while a mixture of block
copolymers and hydrophilic polymers are obtained from
macroinitiators comprising one hydrophobic segment. The hydrophobic
segment may be formed from monomers which will associate, on a
"like prefers like" basis with at least a part of the hydrophobic
network of a polymeric article. For example, in one embodiment
where the article is an ophthalmic device such as a PMMA, siloxane
elastomer or silicone hydrogel contact lens, or a silicone
elastomer punctal plug, the hydrophobic segment is a segment
comprising polysiloxane.
[0016] The hydrophobic-containing macroinitiator may be formed by
reacting a reactive linear polysiloxane having a functional group
such as a hydroxyl group, amino group, thiol group or the like on
at least one terminus with an azo-type initiator having a carboxy
group.
[0017] The reactive linear polysiloxane may be selected from
compounds of the formula:
##STR00001##
[0018] Wherein R.sup.11 is selected from substituted and
unsubstituted C.sub.1-24 alkyl; in some embodiments substituted and
unsubstituted C.sub.1-10 alkyl and in other embodiments
unsubstituted C.sub.1-4 alkyl, and in other embodiments methyl or
n-butyl;
[0019] R.sup.12-R.sup.15 are independently selected from
C.sub.1-C.sub.4 alkyl and C.sub.6-10 aryl; r is 5-60, 6-50, 6-20,
6-15 and in some embodiments 6-12, and R.sup.17, R.sup.18 and
R.sup.19 are independently selected from H, unsubstituted C.sub.1-4
alkyl, C.sub.1-4 alkyl substituted with hydroxyl, amino and the
like and combinations thereof, with the proviso that at least one
of R.sup.17, R.sup.18 and R.sup.19 is a hydrogen atom or comprise a
hydroxyl group, amino group or thiol group.
[0020] The molecular weight of the reactive linear polysiloxane is
between about 300 to about 1800, and in some embodiments between
about 400 to about 1500, about 500 to about 1500, and between about
800 to about 1200.
[0021] Specific examples of reactive linear polysiloxanes
include
##STR00002##
[0022] Wherein m is 0 to 3, and n is r+1 and r is as defined
above.
[0023] The reactive linear polysiloxane is reacted with an azo-type
initiator having a carboxy group or a vinyl group. Suitable
azo-type initiators include 4,4'-azobis(4-cyanovalearic acid) and
its derivatives,
2,2'-azobis[N-(2-carboxyethyl)-2-methylpropionamidine]hydrate,
2,2'-azobis{2-methyl-N-[2-(1-carboxybutyl)]propionamide}, and
2,2'-azobis[2-methyl-N-(2-carboxyethyl)propionamide] and the like.
In one embodiment the azo-type initiator is
4,4'-azobis(4-cyanovalearic acid).
[0024] Generally it is desirable to control the ratio of reactive
linear polysiloxane to azo-type initiator in the reaction. If the
siloxane/initiator molar ratio is too high, siloxane raw material
will remain after reaction, and purifying will be difficult, but if
the ratio is too low (too much initiator), the yield will be
reduced. Therefore ratios of 1 to 2.4, 1.3 to 2.0 and in some
embodiments 1.4 to 1.9 are desirable.
[0025] The azo-type initiator and reactive linear polysiloxane are
reacted via a condensation reaction or a hydrosilylation reaction
at a sufficiently low temperature that the azo type initiator does
not generate radicals. If the reaction temperature is too high,
radicals will be generated from the azo type initiator, but if the
temperature is too low, a long time will be required until the
reaction is complete. Therefore the reaction temperature is
preferably from -20.degree. C. to 50.degree. C., more preferably
from 0.degree. C. to 40.degree. C., and most preferably from
10.degree. C. to 35.degree. C.
[0026] A condensation agent may also be included. Examples of
condensation agents include dicyclohexyl carbodiimide (DCC),
diisopropyl carbodiimide (DIPC), and N-ethyl-N'-3-dimethyl
aminopropyl carbodiimide (EDC=WSCI), as well as hydrochloride salts
(WSCIHCl). A combination of DCC or WSCI and N-hydroxy succinimide
(HONSu), 1-hydroxy benzotriazole (HOBt), or
3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (HOBt) and the like
can also be used. If the amount used is too low, raw material will
remain and purifying will be difficult, but if the amount is too
high, the condensation agent will remain and purifying will be
difficult. Therefore, the molar ratio added is preferably 1.8 to
4.0 times the amount of azo type initiator having a carboxyl group,
and the molar ratio is more preferably 2.0 to 3.0 times, and most
preferably 2.1 to 2.7 times.
[0027] A catalyst can be added during the macro initiator synthesis
reaction of the present invention in order to enhance reactivity.
Suitable catalysts include nucleophilic catalysts such as,
4-dimethyl amino pyridine and the like. If the amount used is too
low, much time will be required for the reaction, but if the amount
is too high, removing the catalyst after the reaction will be
difficult. Therefore molar ratios of catalyst to initiator of about
0.01 to about 4.0, about 0.05 to about 3.0 are desirable. In some
embodiments, in order to prevent raw material from remaining, a
molar ratio of catalyst to initiator about 1.0 to about 2.7 are
preferred.
[0028] In one embodiment, the hydrophobic segment containing
macroinitiators of the present invention have the formula:
##STR00003##
[0029] wherein in (a0) and (a1), R.sup.1 is one type of group
selected from an alkyl group or an alkoxy group;
[0030] R.sup.2 is one type of group selected from (CH.sub.2).sub.n
and (CH.sub.2).sub.m--O(CH.sub.2).sub.n;
[0031] m and n are independent, ranging from 1 to 16, more
preferably from 2 to 10, most preferably from 2 to 5;
[0032] a is from 4 to 19, more preferably from 6 to 17, and most
preferably from 8 to 15;
[0033] b is from 1 to 6, more preferably from 2 to 4; and
[0034] X is one type of group selected from O, NH, and S, more
preferably O, and NH from the viewpoint of high reactivity, and
most preferably O from the viewpoint of less byproduct.
[0035] The hydrophobic segment containing macroinitiators of the
present invention are reacted with at least one hydrophilic monomer
to form the block copolymers of the present invention. In one
embodiment the hydrophilic segment may be formed from known
hydrophilic monomers. Hydrophilic monomers are those which yield a
clear single phase when mixed with water at 25.degree. C. at a
concentration of 10 wt %. Examples of hydrophilic monomers include
vinyl amides, vinylimides, vinyl lactams, hydrophilic
(meth)acrylates, (meth)acrylamides, styrenics, vinyl ethers, vinyl
carbonates, vinyl carbamates, vinyl ureas and mixtures thereof.
[0036] Examples of suitable hydrophilic monomers include N-vinyl
pyrrolidone, N-vinyl-2-piperidone, N-vinyl-2-caprolactam,
N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone,
N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam,
N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone,
vinylimidazole, N--N-dimethylacrylamide, acrylamide,
N,N-bis(2-hydroxyethyl)acrylamide, acrylonitrile, N-isopropyl
acrylamide, vinyl acetate, (meth)acrylic acid, polyethylene glycol
(meth)acrylates, 2-ethyl oxazoline, N-(2-hydroxypropyl)
(meth)acrylamide, N-(2-hydroxyethyl) (meth)acrylamide,
2-methacryloyloxyethyl phosphorylcholine,
3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS),
3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate
(AMPDAPS),
3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate
(MAMPDAPS),
3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate
(APDAPS),
3-((3-methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonat- e
(MAPDAPS), N-vinyl-N-methylacetamide, N-vinylacetamide,
N-vinyl-N-methylpropionamide,
N-vinyl-N-methyl-2-methylpropionamide,
N-vinyl-2-methylpropionamide, N-vinyl-N,N'-dimethylurea, and the
like, and mixtures thereof. In one embodiment the hydrophilic
monomer comprises N-vinyl pyrrolidone, N-vinyl-N-methylacetamide,
2-methacryloyloxyethyl phosphorylcholine, (meth)acrylic acid, N,N
dimethylacrylamide and the like and mixtures thereof. In some
embodiments the hydrophilic segment may also comprise charged
monomers including but not limited to methacrylic acid, acrylic
acid, 3-acrylamidopropionic acid, 4-acrylamidobutanoic acid,
5-acrylamidopentanoic acid, 3-acrylamido-3-methylbutanoic acid
(AMBA), N-vinyloxycarbonyl-.alpha.-alanine,
N-vinyloxycarbonyl-.beta.-alanine (VINAL),
2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VDMO), reactive sulfonate
salts, including, sodium-2-(acrylamido)-2-methylpropane sulphonate
(AMPS), 3-sulphopropyl (meth)acrylate potassium salt,
3-sulphopropyl (meth)acrylate sodium salt, bis 3-sulphopropyl
itaconate di sodium, b is 3-sulphopropyl itaconate di potassium,
vinyl sulphonate sodium salt, vinyl sulphonate salt, styrene
sulfonate, sulfoethyl methacrylate, combinations thereof and the
like. In embodiments where the hydrophilic segment comprises at
least one charged hydrophilic monomer it may be desirable to
include non-charged hydrophilic monomers as comonomers.
[0037] In another embodiment the hydrophilic segment is made from a
hydrophilic polymer selected from a group consisting of
poly-N-vinyl-2-pyrrolidone, poly-N-vinyl-2-piperidone,
poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam,
poly-N-vinyl-3-methyl-2-piperidone,
poly-N-vinyl-4-methyl-2-piperidone,
poly-N-vinyl-4-methyl-2-caprolactam,
poly-N-vinyl-3-ethyl-2-pyrrolidone,
poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinyl imidazole,
poly-N--N-dimethyl acrylamide, poly-N-vinyl-N-methyl acetamide,
polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, and
poly(hydroxyethyl methacrylate), as well as blends and copolymers
thereof. In another embodiment the hydrophilic segment comprises a
hydrophilic polymer selected from a group consisting of
poly-N-vinyl-2-pyrrolidone, poly-N--N-dimethyl acrylamide,
poly-N-vinyl-N-methyl acetamide, polyvinyl alcohol, polyacrylic
acid, polymethacrylic acid, and poly(hydroxyethyl methacrylate) and
copolymers comprising them.
[0038] The hydrophilic monomer should be present in a concentration
sufficient to achieve the desired degree of polymerization of the
hydrophilic segment. If the concentration of hydrophilic monomer is
too high, high viscosity will occur during polymerization, and
mixing will be difficult, and in some cases impossible. Therefore a
weight percentage of 10 to 60 weight % is preferable, and 15 to 50
weight % is most preferable.
[0039] If the monomer/initiator ratio is too low, gelling will
readily occur during polymerization, but if the ratio is too high,
polymerization will not start. Therefore, a ratio of 500 to 10,000
is preferable, 800 to 7000 is more preferable, and 1500 to 5000 is
most preferable.
[0040] The polymerization may be carried out neat or with a
solvent. Suitable solvents include ethers, esters, amides, aromatic
and aliphatic hydrocarbons, alcohols, ketone solvents, ester
solvents, ether solvents, sulfoxide solvents, amide solvents, and
glycol solvents and halohydrocarbons. Among these, from the
viewpoint of hard to inhibit radical polymerization, more
preferable are water, and alcohol solvents, and most preferable are
water and tertiary alcohol solvents. Example include t-amyl
alcohol, diethyl ether, tetrahydrofuran, hexanes, methylene
chloride, ethyl acetate, dimethyl formamide, water, methanol,
ethanol, propanol, 2-propanol, butanol, tert-butanol,
3-methyl-3-pentanol, 3,7-dimethyl-3-octanol, benzene, toluene,
xylene, hexane, heptane, octane, decane, petroleum ether, kerosene,
ligroin, paraffin, acetone, methyl ethyl ketone and methyl isobutyl
ketone, ethyl acetate, butyl acetate, methyl benzoate, dioctyl
phthalate, ethylene glycol diacetate, diethyl ether,
tetrahydrofuran, dioxane, dimethyl sulfoxide,
N,N-dimethylformamide, N,N-dimethylacetamide, ethylene glycol
dialkyl ether, diethylene glycol dialkyl ether, triethylene glycol
dialkyl ether, tetraethylene glycol dialkyl ether, polyethylene
glycol dialkyl ether, polyethylene glycol-polypropylene glycol
block copolymer, and polyethylene glycol-polypropylene glycol
random copolymer, and mixtures thereof and the like. Among these,
from the viewpoint of hard to inhibit radical polymerization, more
preferable are water, tert-butanol, tert-amyl alcohol,
3-methyl-3-pentanol and 3,7-dimethyl-3-octanol. If a solvent is
used it is present in amounts between about 40 to about 90% and in
some embodiments between about 50 and about 85%.
[0041] Any temperature where the selected initiator is active, and
between the freezing and boiling point of the reaction components
(including solvent, if used) may be used. If the temperature is too
high, the polymer solution may also heat excessively and become
difficult to control or dangerous. Temperature ranges between the
10 hour half-life temperature of the polymerization initiator
(hereinafter referred to as T) and T+50.degree. C., and in some
embodiments between T and T+30.degree. C. are suitable.
[0042] Suitable reaction times include up to about 72 hours and in
some embodiments from about 1 to about 24 hours and in other
embodiments from about 2 to about 10 hours.
[0043] The resulting block copolymer may purified via distillation,
column chromatography, precipitation, washing off impurities by
solvent which the block copolymer is insoluble to, fractionation by
GPC, or any other traditional means of polymer isolation.
[0044] The block copolymer may be expressed by formula (b1) or
(b2).
Formula:
##STR00004##
[0046] (wherein in (b1) and (b2), R.sup.1 is one type of group
selected from an alkyl group or an alkoxy group;
[0047] R.sup.2 is one type of group selected from (CH.sub.2).sub.n
or (CH.sub.2).sub.m--O(CH.sub.2).sub.n;
[0048] m and n are independent, ranging from 1 to 16, more
preferably from 2 to 10, most preferably from 2 to 5;
[0049] a is from 4 to 19, more preferably from 6 to 17, and most
preferably from 8 to 15;
[0050] b is from 1 to 6, more preferably from 2 to 4, c is from 1
to 10,000, more preferably from 100 to 8000, and most preferably
from 1000 to 6000,
[0051] X is one type of group selected from O, NH, and S, more
preferably O, and NH from the viewpoint of high reactivity, and
most preferably O from the viewpoint of less byproduct; and
[0052] R.sup.3 and R.sup.4 represent groups made of monomers with
hydrophilicity wherein a monomer is expressed by general formula
(n)).
##STR00005##
[0053] The block copolymers of the present invention have average
molecular weights from about 10,000 to about 3,000,000 more
preferably from about 50,000 to about 1,000,000, and most
preferably from about 100,000 to about 600,000. If the average
molecular weight is too low, the block copolymers will not provide
enough wettability. However, if the average molecular weight is too
high, the viscosity of the block copolymer solution is too high. In
another embodiment, the block copolymers of the invention further
comprising about 0.01 to about 5 weight % of at least one
hydrophobic segment and about 95 to about 99.99 weight % of a
hydrophilic segment, more preferably approximately 0.05 to
approximately 3 weight % of a hydrophobic segment and approximately
97 to approximately 99.95 weight % of a hydrophilic segment, and
most preferably approximately 0.1 to approximately 1 weight % of a
hydrophobic segment and approximately 99 to approximately 99.9
weight % of a hydrophilic segment.
[0054] In some embodiments the block copolymer contains
approximately 0.01 to approximately 5 weight % of a hydrophobic
segment and approximately 95 to approximately 99.9 weight % of a
hydrophilic segment.
[0055] If the silicone (PDMS) block in the block copolymer is too
large, even though the block copolymer overall is hydrophilic due
to the degree of polymerization of the hydrophilic monomer, the
overall solubility of the block copolymer will be insufficient.
However, if the silicone segment is too small the block copolymer
will not persistently associate with the polymeric article and will
not provide the desired benefit over the useful life of the
article.
[0056] The block copolymers of the present invention are
non-reactive. The present invention further relates to polymeric
materials, and in some embodiments medical devices formed from
polymeric materials have the block copolymers of the present
invention associated therewith.
[0057] Suitable medical devices include ophthalmic lenses,
endoscopes, catheters, transfusion tubes, gas transport tubes,
stents, sheaths, cuffs, tube connectors, access ports, drainage
bags, blood circuits, wound covering material, implants and various
types of medicine carriers, but is particularly suitable for
ophthalmic devices, including contact lenses, ophthalmic lenses,
punctal plugs and artificial corneas.
[0058] Where the medical device is an ophthalmic device it may be a
contact lens, corneal implant, punctal plug or the like. Suitable
silicone hydrogel materials are known and may be used, including
but not limited to senofilcon, galyfilcon, lotrafilcon A and
lotrafilcon B, balafilcon, comfilcon and the like. Almost any
silicone hydrogel polymer can be treated using the hydrophilic
polymers of the present invention, including but not limited to
those disclosed in U.S. Pat. No. 6,637,929, WO03/022321,
WO03/022322, U.S. Pat. No. 5,260,000, U.S. Pat. No. 5,034,461, U.S.
Pat. No. 6,867,245, WO2008/061992, U.S. Pat. No. 5,760,100, U.S.
Pat. No. 7,553,880.
[0059] The present invention further relates to optically clear,
aqueous solutions comprising at least one block copolymer of the
present invention in an amount sufficient to reduce at least one of
contact angle, lipid uptake or protein uptake. Suitable amounts
include up to about 5000 ppm, about 50 to about 3000 ppm and about
100 to about 2000 ppm. The block copolymer may be incorporated into
said polymeric article in amounts from about 0.1 ppm to about 30%
of the block copolymer more preferably from about 1000 ppm to about
25%, and most preferably from about 1% to about 20%.
[0060] The hydrophilic polymers of the present invention may be
non-covalently associated with a variety of polymers including
polysiloxanes, silicone hydrogels, polymethyl methacrylate,
polyethylene, polypropylene, polycarbonate, polyethylene
terapthalate, polytetrafluoroethylene, and mixtures thereof and the
like. In this embodiment it is believed that the terminal
polysiloxane associates with the substrate which comprises
hydrophobic polymer components. In this embodiment the block
copolymer is dissolved in a solvent which also swells the
substrate. The polymer substrate is contacted with the solution
comprising the block copolymer. When the substrate is a silicone
hydrogel article, such as a contact lens, suitable solvents include
packing solution, storing solution and cleaning solutions. Using
this embodiment as an example, the silicone hydrogel lens is placed
in a packing solution comprising the block copolymer. The
hydrophilic polymer is present in the solution in amounts between
about 0.001 and about 10%, in some embodiments between about 0.005
and about 2% and in other embodiments between about 0.01 and about
0.5 weight %, based upon all components in the solution.
[0061] The packing solutions of the invention may be any
water-based solution that is used for the storage of contact
lenses. Typical solutions include, without limitation, saline
solutions, other buffered solutions, and deionized water. The
preferred aqueous solution is saline solution containing salts
including, without limitation, sodium chloride, sodium borate,
sodium phosphate, sodium hydrogenphosphate, sodium
dihydrogenphosphate, or the corresponding potassium salts of the
same. These ingredients are generally combined to form buffered
solutions that include an acid and its conjugate base, so that
addition of acids and bases cause only a relatively small change in
pH. The buffered solutions may additionally include
2-(N-morpholino)ethanesulfonic acid (MES), sodium hydroxide,
2,2-bis(hydroxymethyl)-2,2',2''-nitrilotriethanol,
N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, citric
acid, sodium citrate, sodium carbonate, sodium bicarbonate, acetic
acid, sodium acetate, ethylenediamine tetraacetic acid and the like
and combinations thereof. Preferably, the solution is a borate
buffered or phosphate buffered saline solution. The solutions may
also include known additional components such as viscosity
adjusting agents, antimicrobial agents, polyelectrolytes,
stabilizers, chelants, antioxidants, combinations thereof and the
like.
[0062] The substrate is contacted with the block copolymer under
conditions sufficient to incorporate a lubricious and
surface-wetting effective amount of the block copolymer. As used
herein, a lubricious effective amount, is an amount necessary to
impart a level of lubricity which may be felt manually (such as by
rubbing the device between one's fingers) or when the device is
used. Additionally, as used herein, a surface-wetting effective
amount is an amount necessary to impart a level of increased
wetability to the lens, as determined via known contact angle
measurement techniques (i.e. sessile drop, captive bubble, or
dynamic contact angle measurements). It has been found that in one
embodiment, where the device is a soft contact lens, amounts of
hydrophilic polymer as little as 50 ppm provide improved lens
"feel" and lowered surface contact angles, as measured by sessile
drop. Amounts of block copolymer greater than about 50 ppm, and
more preferably amounts greater than about 100 ppm, (measured via
extraction in 2 ml of a 1:1 DMF:deionized water solution, for 72
hours) add a more pronounced improvement in feel. Thus, in this
embodiment, the block copolymer may included in a solution in
concentrations up to about 5000 ppm, in some embodiments between
about 10 and 3000 ppm, and in some embodiments between about 10 and
about 2000 ppm. The packaged lens may be heat treated to increase
the amount of hydrophilic polymer which permeates and becomes
entangled in the lens. Suitable heat treatments, include, but are
not limited to conventional heat sterilization cycles, which
include temperatures of about 120.degree. C. for times of about 20
minutes and may be conducted in an autoclave. If heat sterilization
is not used, the packaged lens may be separately heat treated.
Suitable temperatures for separate heat treatment include at least
about 40.degree. C., and preferably between about 50.degree. C. and
the boiling point of the solution. Suitable heat treatment times
include at least about 10 minutes. It will be appreciated that
higher temperatures will require less treatment time.
[0063] In one embodiment, the polymeric article is formed from a
reactive mixture comprising a silicone monomer comprising a
hydroxyl group.
[0064] Treatment of the polymeric article with the block copolymer
can be performed on the entire polymer or can be performed only on
a portion of the polymer such as only on the surface or a portion
of the surface.
[0065] The present invention will be described in further detail
below through the use of working examples, but the present
invention is not limited to these working examples.
Analytical Methods
(1) GPC Measurement
[0066] GPC measurement was performed at the following
conditions.
[0067] Equipment: Tosoh Corporation
[0068] Column. TSKgel SUPER HM_H, 2 columns (particle diameter; 5
.mu.m, 6.0 mm ID.times.15 cm)
[0069] Mobile phase: N-methylpyrrolidone (10 mM LiBr)
[0070] Column temperature: 40.degree. C.
[0071] Measurement time: 40 minutes
[0072] Injection quantity: 10 .mu.L
[0073] Detector: RI detector
[0074] Flow rate: 0.2 mL/minute
[0075] Sample concentration: 0.4 weight %
[0076] Standard sample: polystyrene (molecular weight 500 to 1.09
million)
(2) Transmission Measurement
[0077] A packaging solution made by dissolving 2000 ppm of block
copolymer was placed in a quartz cell, and a transmissivity was
measured using a color computer (model: SM7-CH) manufactured by
Suga Test Instruments Co., Ltd.
(3) Contact Angle Measurement
[0078] Wettability of lenses was determined using a sessile drop
technique measured using KRUSS DSA-100 .TM. instrument at room
temperature and using DI water as probe solution. The lenses to be
tested (3-5/sample) were rinsed in DI water to remove carry over
from packing solution. Each test lens was placed "bowl side down"
on the convex surface of the lens holder, ensuring proper central
syringe alignment and that the syringe corresponds to the assigned
liquid. Blotting paper (dry Whatman #1 filter paper on a glass
sheet) is gently placed on the lens without any downward pressure
for 20 seconds. A 3 to 4 microliter of DI water drop was formed on
the syringe tip using DSA 100-Drop Shape Analysis software ensuring
the liquid drop was hanging away from the lens. The drop was
released smoothly on the lens surface by moving the needle down.
The needle was withdrawn away immediately after dispensing the
drop. The liquid drop was allowed to equilibrate on the lens for 5
to 10 seconds and the contact angle was computed based on the
contact angle measured between the drop image and the lens
surface.
(4) Lipid Uptake
[0079] A standard curve was set up for each lens type under
investigation. Tagged cholesterol (cholesterol labeled with NBD
([7-nitrobenz-2-oxa-1,3-diazol-4-yl], CH-NBD; Avanti, Alabaster,
Ala.)) was solubilized in a stock solution of 1 mg/mL lipid in
methanol at 35.degree. C. Aliquots were taken from this stock to
make standard curves in phosphate-buffered saline (PBS) at pH 7.4
in a concentration range from 0 to 100 micg/mL.
[0080] One milliliter of standard at each concentration was placed
in the well of a 24-well cell culture plate. 10 lenses of each type
were placed in another 24-well plate and soaked alongside the
standard curve samples in 1 mL of a concentration of 20 micg/ml of
CH-NBD. Another set of lenses (5 lenses) were soaked in PBS without
lipids to correct for any autofluorescence produced by the lens
itself. All concentrations were made up in phosphate buffered
saline (PBS) at pH 7.4. Standard curves, test plates (containing
lenses soaked in CH-NBD) and control plates (containing lenses
soaked in PBS) were all wrapped in aluminum foil to maintain
darkness and were incubated for 24 hours, with agitation at
35.degree. C. After 24 hours the standard curve, test plates and
control plates were removed from the incubator. The standard curve
plates were immediately read on a micro-plate fluorescence reader
(Synergy HT)).
[0081] The lenses from the test and control plates were rinsed by
dipping each individual lens 3 to 5 times in 3 consecutive vials
containing approximately 100 ml of PBS to ensure that only bound
lipid would be determined without lipids carryover. The lenses were
then placed in a fresh 24-well plate containing 1 mL of PBS in each
well and read on the fluorescence reader. After the test samples
were read, the PBS was removed, and 1 mL of a fresh solution of
CH-NBD were placed on the lenses in the same concentrations as
previously mentioned and placed back in the incubator at 35.degree.
C., with rocking, until the next period. This procedure was
repeated for 15 days until complete saturation of lipids on lenses.
Only the lipid amount obtained at saturation was reported.
Working Example 1
[0082] 1.68 g (6 mmol) of 4,4'-azobis(4-cyanovalearic acid) and
1.83 g (15 mmol) of 4-dimethyl amino pyridine, 3.0 g (15 mmol) of
N,N-dicyclohexyl carbodiimide, and 40 mL of acetone were added to a
200 mL three mouth flask equipped with a calcium chloride tube
under nitrogen gas flow. 8.58 g (9 mmol) of polydimethylsiloxane
having a hydroxyl group at one end and expressed by the following
formula (a2)
##STR00006##
(manufactured by Chisso Corporation FM-0411, Mw 1000) was added by
drops to the solution and agitated for six hours at room
temperature. A precipitated solid was filtered out, hexane was
added to the filtrate obtained, and then the filtrate was washed
two times with 0.5 N HCl, two times with saturated sodium
bicarbonate aqueous solution, and one time with saturated sodium
chloride aqueous solution. The organic phase was dried using sodium
sulfate, filtered, and then concentrated to obtain crude product.
The crude product was purified using a silica gel column (silica
gel 180 g, hexane/ethyl acetate=100/0.fwdarw.>10/1 (v/v), 400 mL
each), and 5.18 g of the target silicone macro initiator was
obtained.
Working Example 2
[0083] 1.40 g (5 mmol) of 4,4'-azobis(4-cyanovalearic acid), 9.1 g
(9.1 mmol) of polydimethylsiloxane having an amino group at one end
and expressed by the following formula (a3) (manufactured by Chisso
Corporation, FM0311, Mw 1000), 0.67 g (5.5 mmol) of 4-dimethyl
aminopyridine, and 50 mL of acetone were added to a 200 mL three
mouth flask equipped with a calcium chloride tube under nitrogen
gas flow.
##STR00007##
1.70 mL (11 mmol) of N,N-diisopropyl carbodiimide was added by
drops to this blended solution. After agitating for 6 hours at
ambient temperature, a precipitated solid was filtered out, hexane
was added to the filtrate obtained, and then the filtrate was
washed two times with 0.5 N HCl, two times with saturated sodium
bicarbonate aqueous solution, and one time with saturated sodium
chloride aqueous solution. The organic phase was dried using sodium
sulfate, filtered, concentrated, and then the crude product was
purified using a silica gel column (silica gel 180 g, hexane/ethyl
acetate=10/1.fwdarw.>3/1.fwdarw.>2/1, 300 mL each), and 1.89
g of the target silicone macro initiator was obtained.
Comparative Example 1
[0084] The silicone macro initiator wherein the molecular weight of
the silicone portion is 5000 was obtained by using the same method
as Working Example 1 except that the polydimethylsiloxane
containing a hydroxyl group on one end (a2) was replaced a
polydimethylsiloxane of the same structure, but having a higher
molecular weight (manufactured by Chisso Corporation, FM-0421, Mw
5000). The resulting silicone macroinitiator was purified as
described in Working Example 1.
Comparative Example 2
[0085] The silicone macro initiator wherein the molecular weight of
the silicone portion is 10,000 was obtained by the same method as
Working Example 1 except that the polydimethylsiloxane containing a
hydroxyl group on one end (a2) was replaced a polydimethylsiloxane
of the same structure, but having a higher molecular weight
(manufactured by Chisso Corporation, FM-0425, Mw 10,000), and then
purifying.
Working Example 3
[0086] N-vinyl pyrrolidone (NVP, 29.56 g, 0.266 mol), the silicone
macro initiator expressed by the following formula (a4) obtained by
working example 1 (Mw of silicone portion is 1000, 0.19 g, 0.0866
mmol), and t-amyl alcohol (TAA, 69.42 g) were added to a 200 mL
three mouth flask, and then a three way cock, thermometer, and
mechanical stirrer were attached.
##STR00008##
The inside of the three mouth flask was evacuated using a vacuum
pump and then substituted with argon, three times, and then the
temperature was increased to 70.degree. C. After confirming that
the temperature had stabilized and heat generation was not
occurring, the temperature was increased to 75.degree. C. and the
sample was agitated for 6 hours.
[0087] After polymerization was complete, the temperature was
cooled to room temperature, and then the sample was poured into
n-hexane/ethanol=500 mL/40 mL and allowed to sit. The supernatant
fluid was removed by decanting, and then the washing was performed
2 times using n-hexane/ethanol=500 mL/20 mL. The solid fraction
obtained was dried for 16 hours at 40.degree. C. in a vacuum dryer,
and then liquid nitrogen was added, the sample was crushed using a
spatula, and then transferred to a bag with a zipper. Drying was
performed for 3 hours at 40.degree. C. using a vacuum dryer to
obtain a block copolymer. The molecular weight of the block
copolymer obtained was as shown in Table 1.
Working Examples 4 Through 10
[0088] Additional block copolymers were formed according to the
procedure of Working Example 3, but with the components in the
amounts indicated in Table 1. The molecular weight of the block
copolymer obtained was as shown in Table 1.
Working Example 11
[0089] N-vinyl pyrrolidone (NVP, 31.12 g, 0.28 mol), the silicone
macro initiator expressed by the following formula (a5) obtained by
Working Example 1 (Mw of silicone portion is 1000, 0.15 g, 0.07
mmol), and t-amyl alcohol (TAA, 72.96 g) were added to a 200 mL
three mouth flask, and then a three way cock, thermometer, and
mechanical stirrer were attached.
##STR00009##
The inside of the three mouth flask was evacuated using a vacuum
pump and then substituted with argon, three times, and then the
temperature was increased to 70.degree. C. After confirming that
the temperature had stabilized and heat generation was not
occurring, the temperature was increased to 75.degree. C. and the
sample was agitated for 6 hours.
[0090] After polymerization was complete, the temperature was
cooled to room temperature, and then the sample was poured into
n-hexane/ethanol=600 mL/20 mL and allowed to sit. The supernatant
fluid was removed by decanting, and then the washing was performed
2 times using n-hexane/ethanol=500 mL/20 mL. The solid fraction
obtained was dried for 16 hours at 40.degree. C. in a vacuum dryer,
and then liquid nitrogen was added, the sample was crushed using a
spatula, and then transferred to a bag with a zipper. Drying was
performed for 3 hours at 40.degree. C. using a vacuum dryer to
obtain a block copolymer. The molecular weight of the block
copolymer obtained was as shown in Table 1.
Working Examples 12 Through 13
[0091] Additional block copolymers were formed according to the
procedure of Working Example 11, but with the components in the
amounts indicated in Table 1. The molecular weight of the block
copolymer obtained was as shown in Table 1.
Comparative Example 3
[0092] Polymerization was performed by the same method as Working
Example 3, except that the polymerization initiator was substituted
with the silicone macroinitiator of Comparative Example 1
(molecular weight (Mw) of the silicone portion 5000), and the
amounts of the components used were as indicated in Table 1. The
molecular weight of the block copolymer obtained was as shown in
Table 1.
Comparative Example 4 and 5
[0093] Polymerization was performed by the same method as Working
Example 3, except that the polymerization initiator was substituted
with a silicone macroinitiator of Comparative Example 2 (molecular
weight (Mw) of the silicone portion 10,000), and the amounts of the
components used were as indicated in Table 1. The molecular weight
of the block copolymer obtained was as shown in Table 1.
TABLE-US-00001 TABLE 1 NVP macro-initiator TAA Mn Mw Ex. # (g) Ex#
(g) (g) (kD) (kD) 3 29.56 1 0.19 69.42 113.3 293.9 4 24.62 1 0.19
24.81 132.0 509.0 5 25.9 1 0.19 39.15 148.5 505.0 6 15.54 1 0.2
36.9 48.5 135.4 7 31.07 1 0.1 72.73 78.4 189.2 8 5.18 1 0.1 29.92
42.7 93.8 9 19.45 1 0.15 45.73 88.7 251.6 10 31.10 1 0.15 72.92
70.9 198.1 11 31.12 2 0.15 72.96 80.0 228.8 12 23.34 2 0.15 35.24
103.1 353.7 13 23.34 2 0.15 23.49 114.6 406.8 CE3 15.34 CE1 0.46
36.87 69.9 183.9 CE4 16.67 CE2 1.0 41.23 68.69 172.39 CE5 44.46 CE2
1.0 106.1 67.96 166.94
Working Example 14
[0094] Polymerization was performed by the same method as Working
Example 3, except that NVP was substituted with
N,N-dimethylacrylamide (DMA), and the amounts of the components
used were as indicated in Table 2. The molecular weight of the
block copolymer obtained was as shown in Table 2.
Working Example 15 Through 16
[0095] Additional block copolymers were formed according to the
procedure of Working Example 14, but with the components in the
amounts indicated in Table 2. The molecular weight of the block
copolymer obtained was as shown in Table 2.
TABLE-US-00002 TABLE 2 DMA macro-initiator TAA Mn Mw Ex. # (g) Ex#
(g) (g) (kD) (kD) 14 17.4 1 0.15 40.8 222.5 582.8 15 34.7 1 0.15
81.3 263.4 693.3 16 26.4 1 0.19 62.0 204.1 728.4
Working Example 17
[0096] The block copolymers obtained by Working Examples 3 through
8 and 11 through 14, as well as comparative examples 3 through 5
were dissolved at a concentration of 2000 ppm in packaging
solutions. The transmissivity of the solutions obtained was
measured and are shown in Table 3.
TABLE-US-00003 TABLE 3 Silicone portion Block copolymer
Transmissivity Ex# Mw Mn (kD) Mw (kD) (%) Transparency 3 1000 113.3
293.9 97.37 Transparent 4 1000 132.0 509.0 96.97 Transparent 5 1000
148.5 505.0 96.38 Transparent 6 1000 48.5 135.4 97.76 Transparent 7
1000 78.4 189.2 96.74 Transparent 8 1000 42.7 93.8 93.65
Transparent 11 1000 80.0 228.8 98.57 Transparent 12 1000 103.1
353.7 98.38 Transparent 13 1000 114.6 406.8 97.30 Transparent 14
1000 204.1 728.4 97.37 Transparent CE3 5000 69.9 183.9 91.39 White
cloudy CE4 10,000 68.69 172.39 78.63 White cloudy CE5 10,000 67.96
166.94 89.38 White cloudy
[0097] As shown in Table 3, the copolymers of Examples 3 through 8
and 11-14 all formed transparent solutions, even at 2000 ppm. When
the molecular weight of the siloxane segment was above about 5000
(Comparative Examples 3 through 5) the transmissivity of the 2000
ppm solution was reduced and a clear solution could not be
obtained.
Working Example 18
[0098] ACUVUE OASYS with Hydraclear Plus contact lenses (senofilcon
A) were immersed in packaging solutions obtained by dissolving 2000
ppm of the block copolymers obtained in Working Examples 3, 9, and
10, and then immersing for 24 hours in a packaging solution that
did not contain the block copolymer. The samples were removed and
the contact angle was measured. The results are shown in Table 4. A
lipid uptake test was also performed, and the results are shown in
Table 4. All of the lenses were found to have reduced lipid uptake
compared to the lenses which were not soaked in the block
copolymers.
TABLE-US-00004 TABLE 4 Copolymer Contact lipid uptake Ex# angle
(.degree.) (.mu.g/lens) No treatment 53 28.2 3 38 14.4 9 69 14.8 10
57 15.1
* * * * *