U.S. patent application number 12/333345 was filed with the patent office on 2009-07-02 for segmented reactive block copolymers.
Invention is credited to Jay F. Kunzler, Jeffrey G. Linhardt, Devon A. Shipp.
Application Number | 20090171049 12/333345 |
Document ID | / |
Family ID | 40797822 |
Filed Date | 2009-07-02 |
United States Patent
Application |
20090171049 |
Kind Code |
A1 |
Linhardt; Jeffrey G. ; et
al. |
July 2, 2009 |
SEGMENTED REACTIVE BLOCK COPOLYMERS
Abstract
This invention is directed toward reactive segmented block
copolymers useful to treat the surface of a substrate by means of
reactive functionalities of the reactive segmented block copolymer
material reacting with complementary surface reactive
functionalities of the polymer substrate.
Inventors: |
Linhardt; Jeffrey G.;
(Fairport, NY) ; Shipp; Devon A.; (Potsdam,
NY) ; Kunzler; Jay F.; (Canandaigua, NY) |
Correspondence
Address: |
Bausch & Lomb Incorporated
One Bausch & Lomb Place
Rochester
NY
14604-2701
US
|
Family ID: |
40797822 |
Appl. No.: |
12/333345 |
Filed: |
December 12, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61016844 |
Dec 27, 2007 |
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61016845 |
Dec 27, 2007 |
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61016841 |
Dec 27, 2007 |
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61016843 |
Dec 27, 2007 |
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Current U.S.
Class: |
526/264 ;
528/363 |
Current CPC
Class: |
C08J 7/056 20200101;
C08F 293/005 20130101; C08J 2383/00 20130101; A61M 25/0045
20130101; C08F 2438/03 20130101; C08F 130/08 20130101; Y10T
428/31663 20150401; C08F 230/00 20130101; Y10T 428/31536 20150401;
A61L 27/34 20130101; G02B 1/043 20130101; C08J 2343/04 20130101;
A61L 31/10 20130101 |
Class at
Publication: |
526/264 ;
528/363 |
International
Class: |
C08F 26/10 20060101
C08F026/10; C08G 69/40 20060101 C08G069/40 |
Claims
1. A reactive segmented block copolymer comprising a chemical
binding unit block and a hydrophilic block.
2. The reactive segmented block copolymer of claim 1 wherein the
chemical binding unit is selected from the group consisting of
monomers comprising a functionality selected from the group
consisting of epoxides, carboxylic acids, anhydrides, oxazolinones,
lactams, lactones, amines, hydroxys, hydrazines, hydrazides,
thiols, nucleophilic groups, electrophilic groups, carboxylic
esters, imide esters, orthoesters, carbonates, isocyanates,
isothiocyanates, aldehydes, ketones, thiones, alkenyls, acrylates,
methacrylates, acrylamides, sulfones, maleimides, disulfides,
iodos, sulfonates, thiosulfonates, silanes, alkoxysilanes,
halosilanes, phosphoramidate and alcohol functionality.
3. The reactive segmented block copolymer of claim 1 wherein the
hydrophilic block comprises monomers selected from the group
consisting of 2-hydroxyethyl methacrylate, glycerol methacrylate,
methacrylic acid, acrylic acid, methacrylamide, acrylamide,
N,N'-dimethylmethacrylamide, N,N'-dimethylacrylamide; ethylenically
unsaturated poly(alkylene oxide)s, cyclic lactams,
N-vinyl-2-pyrrolidone, hydrophilic vinyl carbonate, hydrophilic
vinyl carbamate monomers, 2-hydroxyethyl acrylate,
2-(2-ethoxyethoxy)ethyl(meth)acrylate, glyceryl(meth)acrylate,
poly(ethylene glycol (meth)acrylate),
tetrahydrofurfuryl(meth)acrylate, N-vinyl acetamide, copolymers,
derivatives and combinations thereof.
4. The reactive segmented block copolymer of claim 1 wherein the
block of the chemical binding unit comprises between 1 and about
1,000 units.
5. The reactive segmented block copolymer of claim 1 wherein the
block of the chemical binding unit comprises between 1 and about
100 units.
6. The reactive segmented block copolymer of claim 1 wherein the
block of the chemical binding unit comprises between 1 and about 30
units.
7. The reactive segmented block copolymer of claim 1 wherein the
hydrophilic block comprises between 1 and about 10,000 units.
8. The reactive segmented block copolymer of claim 1 wherein the
hydrophilic block comprises between about 10 and about 1,000
units.
9. The reactive segmented block copolymer of claim 1 wherein the
hydrophilic block comprises between about 20 and about 300
units.
10. A reactive segmented block copolymer having the following
generic formula (I): R1-[(A)m]p-[(B)n]q-X (I) wherein R1 is a
reactive residue of a moiety capable of acting as an initiator for
Atom Transfer Radical Polymerization, A is a chemical binding unit
block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to
10,000, p and q are natural numbers, and X is a halogen capping
group of an initiator for Atom Transfer Radical Polymerization or a
derivatized reaction product.
11. A reactive segmented block copolymer having the following
generic formula (II): R1-[(A)m]p-[(B)n]q-R2 (II) wherein R1 is a
radical forming residue of a RAFT agent or free radical initiator,
A is a chemical binding unit block, B is a hydrophilic unit block,
m is I to 10,000, n is 1 to 10,000, p and q are natural numbers,
and R2 is a thio carbonyl fragment of the chain transfer agent or a
derivatized reaction product.
12. The reactive segmented block copolymer of claim 1 wherein the
chemical binding unit block is an epoxy containing vinylic
monomer.
13. The reactive segmented block copolymer of claim 12 wherein the
epoxy containing vinylic monomer is glycidyl methacrylate.
14. The reactive segmented block copolymer of claim 12 wherein the
epoxy containing monomer is glycidyl vinyl carbamate or glycidyl
vinyl carbonate.
15. The reactive segmented block copolymer of claim 1 wherein the
chemical binding unit is glycidyl methacrylate and the hydrophilic
block comprises N,N-dimethylacrylamide.
16. The reactive segmented block copolymer of claim 1 wherein the
chemical binding unit block comprises glycidyl vinyl carbonate or
glycidyl vinyl carbamate and the hydrophilic block comprises
n-vinyl pyrolidone.
17. The reactive segmented block copolymer of claim 1 wherein the
chemical binding unit is about 15 units of glycidyl methacrylate
and the hydrophilic block comprises about 100 units of
N,N-dimethylacrylamide.
18. The reactive segmented block copolymer of claim 1 wherein the
chemical binding unit block is about 15 units of glycidyl vinyl
carbonate or glycidyl vinyl carbamate and the hydrophilic block
comprises about 100 units of n-vinyl pyrolidone.
19. A reactive segmented block copolymer having the following
generic formula (III): R1-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q-R1
(III) wherein R1 is a radical forming residue of a RAFT agent or
free radical initiator, A is a chemical binding unit block, B is a
hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q
are natural numbers, and R2 is a thio carbonyl thio group.
20. The reactive segmented block copolymer of claim 10 wherein one
of the chemical binding unit block or the hydrophilic block is a
statistical copolymerization or compositionally heterogeneous
block.
21. The reactive segmented block copolymer of claim 11 wherein one
of the chemical binding unit block or the hydrophilic block is a
statistical copolymerization or compositionally heterogeneous
block.
22. The reactive segmented block copolymer of claim 19 wherein one
of the chemical binding unit block or the hydrophilic block is a
statistical copolymerization or compositionally heterogeneous
block.
23. The reactive segmented block copolymer of claim 10 further
comprising at least one block selected from the group consisting of
nonbinding blocks, nonhydrophilic blocks and combinations
thereof.
24. The reactive segmented block copolymer of claim 11 further
comprising at least one block selected from the group consisting of
nonbinding blocks, nonhydrophilic blocks and combinations
there.
25. The reactive segmented block copolymer of claim 19 further
comprising at least one block selected from the group consisting of
nonbinding blocks, nonhydrophilic blocks and combinations thereof.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of Provisional Patent
Application No. 61/016,844 filed Dec. 27, 2007; Provisional Patent
Application No. 61/016,845 filed Dec. 27, 2007; Provisional Patent
Application No. 61/016,841 filed Dec. 27, 2007; and Provisional
Patent Application No. 61/016,843 filed Dec. 27, 2007.
FIELD OF INVENTION
[0002] This invention relates to a new class of tailored polymers
useful as surface coatings for ophthalmic devices. These polymers
can be specifically tailored using controlled radical
polymerization processes and contain functional domains. Controlled
radical polymerization allows the facile synthesis of segmented
block copolymers with tunable chemical composition that, as a
result, show different chemical properties than those prepared via
conventional free radical polymerization. Segmented block
copolymers with substrate binding domain(s) containing functional
groups (glycidyl groups, activated esters, amino groups, hydroxyl
groups, carboxylic acid groups, etc.) and hydrophilic domain(s)
show good surface properties when covalently bound to substrates
containing complimentary functionality.
BACKGROUND OF THE INVENTION
[0003] Medical devices such as ophthalmic lenses are made from a
wide variety of materials. In the contact lens field materials are
broadly categorized into conventional hydrogels or silicone
hydrogels. Recently, the use of silicone-containing materials
(silicone hydrogels) has been preferred. These materials can vary
greatly in water content. However, regardless of their water
content, silicone materials tend to be relatively hydrophobic,
non-wettable, and have a high affinity for lipids. Methods to
modify the surface of silicone devices by increasing their
hydrophilicity and improving their biocompatibility are of great
importance.
[0004] A number of copolymers for surface coatings have been
investigated. U.S. Pat. No. 6,958,169 discloses providing a medical
device formed from a monomer mixture comprising a hydrophilic
device-forming monomer including a copolymerizable group and an
electron donating moiety, and a second device-forming monomer
including a copolymerizable group and a reactive functional group;
and, contacting a surface of the medical device with a wetting
agent including a proton donating moiety reactive with the
functional group provided by the second lens-forming monomer and
that complexes with the electron donating moiety provided by the
hydrophilic lens-forming monomer.
[0005] U.S. Pat. No. 6,858,310 discloses a method of modifying the
surface of a medical device to increase its biocompatibility or
hydrophilicity by coating the device with a removable hydrophilic
polymer by means of reaction between reactive functionalities on
the hydrophilic polymer with functionalities that are complementary
on or near the surface of the medical device.
[0006] U.S. Pat. No. 6,599,559 discloses a method of modifying the
surface of a medical device to increase its biocompatibility or
hydrophilicity by coating the device with a removable hydrophilic
polymer by means of reaction between reactive functionalities on
the hydrophilic polymer which functionalities are complementary to
reactive functionalities on or near the surface of the medical
device.
[0007] U.S. Pat. No. 6,428,839 discloses a method for improving the
wettability of a medical device, comprising the steps of: (a)
providing a medical device formed from a monomer mixture comprising
a hydrophilic monomer and a silicone-containing monomer, wherein
said medical device has not been subjected to a surface oxidation
treatment; (b) contacting a surface of the medical device with a
solution comprising a proton-donating wetting agent, whereby the
wetting agent forms a complex with the hydrophilic monomer on the
surface of the medical device in the absence of a surface oxidation
treatment step and without the addition of a coupling agent.
[0008] Many copolymers are currently made using conventional free
radical polymerization techniques with the structure of the polymer
being completely random or controlled by the reactivity ratios of
the respective monomers. By using controlled free radical
polymerization techniques one is able to assemble copolymers in a
controlled fashion and, in turn, they show completely different
solution and coating properties than copolymers prepared using
conventional free radical polymerization techniques. Controlled
free radical polymerization can be conducted by a variety of
methods, such as ATRP (atom transfer radical polymerization) and
RAFT (Reversible addition-fragmentation chain transfer
polymerization).
SUMMARY
[0009] In accordance with the present disclosure, the invention
relates generally to reactive segmented block copolymers useful for
forming bound coatings in the manufacture of medical devices. As
used herein the terms "bound", "binding", or terms of similar
import, refer to covalent linkages between the reactive segmented
block copolymer and the surface functionality of the device which
results in the association of a coating composition with the
device. Examples of suitable devices include contact lenses,
intraocular lenses, intraocular lens inserters, vascular stents,
phakic intraocular lenses, aphakic intraocular lenses, corneal
implants, catheters, implants, and the like.
[0010] Reactive segmented block copolymers prepared through Atom
Transfer Radical Polymerization ("ATRP") methods in accordance with
the invention herein have the following generic formula (I):
R.sub.1-[(A).sub.m].sub.p-[(B).sub.n].sub.q--X (I)
wherein R.sub.1 is the reactive residue of a moiety capable of
acting as an initiator for Atom Transfer Radical Polymerization, A
is a chemical binding unit block, B is a hydrophilic unit block, m
is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and
X is a halogen capping group of the initiator for Atom Transfer
Radical Polymerization. It should be noted, that there are many
processes for the post polymerization removal or transformation of
the halogen capping group of an initiator for Atom Transfer Radical
Polymerization which are known to one of ordinary skill in the art.
Therefore polymers prepared using ATRP according to the invention
herein would include those where X is a halogen capping group of
the initiator for Atom Transfer Radical Polymerization and those
polymers that have undergone post polymerization removal or
transformation of the halogen capping group of an initiator for
Atom Transfer Radical Polymerization (i.e., derivatized reaction
product). The polymers which contain halogen end-groups can be
utilized in a host of traditional alkyl halide organic reactions.
In one example, the addition of tributyltin hydride to the
polymeric alkyl halide in the presence of a radical source (AIBN,
or Cu(I) complex) leads to a saturated hydrogen-terminated polymer.
In another example, by replacing tributyltin hydride with allyl
tri-n-butylstannane, polymers with allyl end groups can be
prepared. The terminal halogen can also be displaced by
nucleophilic substitution, free-radical chemistry, or electrophilic
addition catalyzed by Lewis acids to yield a wide variety of
telechelic derivatives, such as alkenes, alkynes, alcohols, thiols,
alkanes, azides, amines, phosphoniums, or epoxy groups, to mention
a few.
[0011] Reactive segmented block copolymers prepared through
Reversible addition-fragmentation chain transfer polymerization
("RAFT") methods in accordance with the invention herein have the
following generic formula (II):
R.sub.1-[(A).sub.m].sub.p-[(B).sub.n].sub.q--R.sub.2 (II)
wherein R.sub.1 is a radical forming residue of a RAFT agent or
free radical initiator, A is a chemical binding unit block, B is a
hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q
are natural numbers, and R.sub.2 is a thio carbonyl thio fragment
of the chain transfer agent. RAFT agents based upon thio carbonyl
thio chemistry are well known to those of ordinary skill in the art
and would include, for example, xanthates, trithiocarbonates and
dithio esters. It should be noted, that there are many processes
for the post polymerization removal or transformation of the thio
carbonyl thio fragment of the chain transfer agent which are known
to one of ordinary skill in the art. Therefore polymers prepared
using RAFT agent according to the invention herein would include
those where R.sub.2 is a thio carbonyl thio fragment of the chain
transfer agent and those polymers that have undergone post
polymerization removal or transformation of the thio carbonyl thio
fragment of the chain transfer agent (i.e., a derivatized reaction
product). One example of such a transformation is the use of free
radical reducing agents to replace the thio carbonyl thio group
with hydrogen. Others include thermolysis of the end group or
conversion of the thio carbonyl thio groups to thiol groups by
aminolysis. A wide variety of telechelic derivatives can be
prepared, such as alkenes, alkynes, alcohols, thiols, alkanes,
azides, amines, phosphoniums, or epoxy groups, to mention a
few.
[0012] Reactive segmented block copolymers prepared through
reversible addition-fragmentation chain transfer polymerization
("RAFT") methods in accordance with the invention herein have the
following generic formula (III):
R1-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q-R1 (III)
wherein R1 is a radical forming residue of a RAFT agent or free
radical initiator, A is a chemical binding unit block, B is a
hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q
are natural numbers, and R2 is a thio carbonyl thio group.
[0013] For each of the polymers of generic formula I, II and III
the order of the block units is not critical and the reactive
segmented block copolymer can contain more than two blocks.
Therefore the reactive segmented block copolymers can be multiblock
copolymers and include repetition of one or more blocks. As
examples please see the nonlimiting representations below, each of
which is intended to fall within generic formula I, II and III:
TABLE-US-00001 (1) -(A).sub.m-(B).sub.n- (2) -(B).sub.n-(A).sub.m-
(3) -(A).sub.m-(B).sub.n-(A).sub.m-
[0014] Reactive segmented block copolymers according to the
invention herein may also contain blocks that would not be
considered to be binding or hydrophilic, for example, polystyrene
or polymethyl methacrylate. The presence of non binding or non
hydrophilic block(s) within a polymer is contemplated as being
within the scope of the claimed reactive segmented block copolymers
and formulae I, II and III of the invention herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a schematic example of atom-transfer radical
polymerization (ATRP) used to make a segmented block copolymer in
which there is an oligomeric block of the chemical binding unit at
one end of the polymer followed by a large hydrophilic block;
[0016] FIG. 2 is the structural formula of various monomers which
may be used to provide the reactive functionality of the segmented
block copolymers of the invention herein;
[0017] FIG. 3 is a reaction schematic showing how RAFT
polymerization can be used to polymerize block copolymers with
functional domains.
DETAILED DESCRIPTION
[0018] The present invention relates generally to reactive
segmented block copolymers. The reactive segmented block copolymers
are useful in various compositions including ophthalmic
compositions comprising the reactive segmented block copolymers for
use in providing surface bound coatings in the manufacture of
medical devices. In preferred embodiments, the present invention
relates to reactive segmented block copolymers having reactive
functionality that is complimentary to surface functionality of a
medical device such as an ophthalmic lens. It should be understood
that the term "surface" is not to be limited to meaning "at least
one complete surface". Surface coverage does not have to be even or
complete to be effective for surface functionality or surface
treatment. The reactive segmented block copolymers of the present
invention are useful as coatings for biocompatible materials
including both soft and rigid materials commonly used for
ophthalmic lenses, including contact lenses.
[0019] Reactive segmented block copolymers prepared through Atom
Transfer Radical Polymerization ("ATRP") methods in accordance with
the invention herein have the following generic formula (I):
R.sub.1-[(A).sub.m].sub.p-[(B).sub.n].sub.q--X (I)
wherein R.sub.1 is the reactive residue of a moiety capable of
acting as an initiator for Atom Transfer Radical Polymerization, A
is a chemical binding unit block, B is a hydrophilic unit block, m
is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, and
X is a halogen capping group of the initiator for Atom Transfer
Radical Polymerization. It should be noted, that there are many
processes for the post polymerization removal or transformation of
the halogen capping group of an initiator for Atom Transfer Radical
Polymerization which are known to one of ordinary skill in the art.
Therefore polymers prepared using ATRP according to the invention
herein would include those where X is a halogen capping group of
the initiator for Atom Transfer Radical Polymerization and those
polymers that have undergone post polymerization removal or
transformation of the halogen capping group of an initiator for
Atom Transfer Radical Polymerization (i.e., derivatized reaction
product). The polymers which contain halogen end-groups can be
utilized in a host of traditional alkyl halide organic reactions.
In one example, the addition of tributyltin hydride to the
polymeric alkyl halide in the presence of a radical source (AIBN,
or Cu(I) complex) leads to a saturated hydrogen-terminated polymer.
In another example, by replacing tributyltin hydride with allyl
tri-n-butylstannane, polymers with allyl end groups can be
prepared. The terminal halogen can also be displaced by
nucleophilic substitution, free-radical chemistry, or electrophilic
addition catalyzed by Lewis acids to yield a wide variety of
telechelic derivatives, such as alkenes, alkynes, alcohols, thiols,
alkanes, azides, amines, phosphoniums, or epoxy groups, to mention
a few.
[0020] Reactive segmented block copolymers prepared through
Reversible addition-fragmentation chain transfer polymerization
("RAFT") methods in accordance with the invention herein have the
following generic formula (II):
R.sub.1-[(A).sub.m].sub.p-[(B).sub.n].sub.q--R.sub.2 (II)
wherein R.sub.1 is a radical forming residue of a RAFT agent or
free radical initiator, A is a chemical binding unit block, B is a
hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q
are natural numbers, and R.sub.2 is a thio carbonyl thio fragment
of the chain transfer agent. RAFT agents based upon thio carbonyl
thio chemistry are well known to those of ordinary skill in the art
and would include, for example, xanthates, trithiocarbonates and
dithio esters. It should be noted, that there are many processes
for the post polymerization removal or transformation of the thio
carbonyl thio fragment of the chain transfer agent which are known
to one of ordinary skill in the art. Therefore polymers prepared
using RAFT agent according to the invention herein would include
those where R.sub.2 is a thio carbonyl thio fragment of the chain
transfer agent and those polymers that have undergone post
polymerization removal or transformation of the thio carbonyl thio
fragment of the chain transfer agent (i.e., a derivatized reaction
product). One example of such a transformation is the use of free
radical reducing agents to replace the thio carbonyl thio group
with hydrogen. Others include thermolysis of the end group or
conversion of the thio carbonyl thio groups to thiol groups by
aminolysis. A wide variety of telechelic derivatives can be
prepared, such as alkenes, alkynes, alcohols, thiols, alkanes,
azides, amines, phosphoniums, or epoxy groups, to mention a
few.
[0021] Reactive segmented block copolymers prepared through
reversible addition-fragmentation chain transfer polymerization
("RAFT") methods in accordance with the invention herein have the
following generic formula (III):
R1-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q-R1 (III)
wherein R1 is a radical forming residue of a RAFT agent or free
radical initiator, A is a chemical binding unit block, B is a
hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q
are natural numbers, and R2 is a thio carbonyl thio group.
[0022] For each of the polymers of generic formula I, II and III
the order of the block units is not critical and the reactive
segmented block copolymer can contain more than two blocks.
Therefore the reactive segmented block copolymers can be multiblock
copolymers and include repetition of one or more blocks. As
examples please see the nonlimiting representations below, each of
which is intended to fall within generic formula I, II and III:
TABLE-US-00002 (1) -(A).sub.m-(B).sub.n- (2) -(B).sub.n-(A).sub.m-
(3) -(A).sub.m-(B).sub.n-(A).sub.m-
[0023] Reactive segmented block copolymers according to the
invention herein may also contain blocks that would not be
considered to be binding or hydrophilic, for example, polystyrene
or polymethyl methacrylate. The presence of non binding or non
hydrophilic block(s) within a polymer is contemplated as being
within the scope of the claimed reactive segmented block copolymers
and formulae I, II and III of the invention herein.
[0024] The present invention provides materials useful for surface
modifying contact lenses and like medical devices through the use
of complementary functionality. Although only contact lenses will
be referred to hereinafter for purposes of simplicity, such
reference is not intended to be limiting since the subject
copolymers are suitable for surface modification of other medical
devices such as phakic and aphakic intraocular lenses and corneal
implants as well as contact lenses. Surface groups of the polymeric
materials of the contact lenses and other biomedical devices are
used to form chemical linkages, i.e., binding, with the reactive
segmented block copolymers of the invention herein. The preferred
reactive segmented block copolymers in the present invention are
selected based on the specific surface groups of the polymeric
material to be coated. In accordance with the present invention,
the one or more reactive segmented block copolymers selected for
surface modification should have complementary reactive chemical
functionality to that of the surface groups of the substrate. Such
complementary reactive chemical functionality enables a chemical
reaction between the reactive segmented block copolymers and the
complementary surface groups of the substrate to form covalent
linkages there between. The one or more reactive segmented block
copolymers are thus bound to the surface of the contact lens or
like medical device to achieve surface modification thereof.
[0025] The reactive segmented block copolymer comprises a chemical
binding unit block to provide the desired surface binding of the
molecule. The chemical binding unit block can be varied and is
determined based upon the intended use of the reactive segmented
block copolymers. That is, the chemical binding unit block of the
reactive segmented block copolymers is selected to provide
functionality that is complementary with the surface functionality
of the device.
[0026] Selection of the chemical binding unit monomer of the block
copolymer is determined by the functional groups on the surface of
the device. For example, if the reactive molecule on the surface of
the device contains a carboxylic acid group, a glycidyl group
containing monomer can be a chemical binding unit monomer of the
reactive segmented block copolymer. If the reactive molecule on the
surface of the device contains hydroxy or amino functionality, an
isocyanate group or carbonyl chloride group containing monomers can
be a chemical binding unit monomer of the reactive segmented block
copolymer. A wide variety of suitable combinations of functional
group containing monomers of the chemical binding unit
complementary to reactive groups on the surface of the device will
be apparent to those of ordinary skill in the art. For example, the
chemical binding unit block may comprise a moiety selected from
amine, hydroxyl, hydrazine, hydrazide, thiol (nucleophilic groups),
carboxylic acid, carboxylic ester, including imide ester,
orthoester, carbonate, isocyanate, isothiocyanate, aldehyde,
ketone, thione, alkenyl, acrylate, methacrylate, acrylamide,
sulfone, maleimide, disulfide, iodo, epoxy, sulfonate,
thiosulfonate, silane, alkoxysilane, halosilane, and
phosphoramidate. More specific examples of these groups include
succinimidyl ester or carbonate, imidazolyl ester or carbonate,
benzotriazole ester or carbonate, p-nitrophenyl carbonate, vinyl
sulfone, chloroethylsulfone, vinylpyridine, pyridyl disulfide,
iodoacetamide, glyoxal, dione, mesylate, tosylate, and tresylate.
Also included are other activated carboxylic acid derivatives, as
well as hydrates or protected derivatives of any of the above
moieties (e.g. aldehyde hydrate, hemiacetal, acetal, ketone
hydrate, hemiketal, ketal, thioketal, thioacetal). Preferred
electrophilic groups include succinimidyl carbonate, succinimidyl
ester, maleimide, benzotriazole carbonate, glycidyl ether,
imidazoyl ester, p-nitrophenyl carbonate, acrylate, tresylate,
aldehyde, and orthopyridyl disulfide. Examples of complementary
functionality are provided below in Table 1.
TABLE-US-00003 TABLE 1 MONOMER/RESIDUE HAVING A REACTIVE FUNCTIONAL
COMPLEMENTARY REACTIVE GROUP SURFACE FUNCTIONALITY Carboxylic acid,
isocyanate, Alcohol, amine, thiol , epoxy epoxy, anhydride,
lactone, lactam, oxazolone, maleimide, anhydride, acrylates,
##STR00001## Amine, thiol, alcohol, ##STR00002## Carboxylic acid,
isocyanate, epoxy, anhydride, lactone, lactam, oxazolone,
maleimide, anhydride, acrylates
[0027] The chemical binding unit block of the reactive segmented
block copolymers is oligomeric or polymeric and is sized to provide
suitable binding to the surface of the medical device to be coated.
Therefore the variable m of formula I, II or III can be between 1
and about 1000, preferably between 1 and about 100, most preferably
between 1 and about 30.
[0028] In addition to the chemical binding unit, the reactive
segmented block copolymers of the invention herein will also
contain hydrophilic domain(s) showing good surface properties when
the block copolymer is covalently bound to substrates containing
complimentary functionality. The hydrophilic domain(s) will
comprise at least one hydrophilic monomer, such as, HEMA, glyceryl
methacrylate, methacrylic acid ("MAA"), acrylic acid ("AA"),
methacrylamide, acrylamide, N,N'-dimethylmethacrylamide, or
N,N'-dimethylacrylamide; copolymers thereof; hydrophilic
prepolymers, such as ethylenically unsaturated poly(alkylene
oxide)s, cyclic lactams such as N-vinyl-2-pyrrolidone ("NVP"), or
derivatives thereof. Still further examples are the hydrophilic
vinyl carbonate or vinyl carbamate monomers. Hydrophilic monomers
can be nonionic monomers, such as 2-hydroxyethyl methacrylate
("HEMA"), 2-hydroxyethyl acrylate ("HEA"), 2-(2-ethoxyethoxy)ethyl
(meth)acrylate, glyceryl (meth)acrylate, poly(ethylene glycol
(meth)acrylate), tetrahydrofurfuryl (meth)acrylate,
(meth)acrylamide, N,N'-dimethylmethacrylamide,
N,N'-dimethylacrylamide("DMA"), N-vinyl-2-pyrrolidone (or other
N-vinyl lactams), N-vinyl acetamide, and combinations thereof.
Still further examples of hydrophilic monomers are the vinyl
carbonate and vinyl carbamate monomers disclosed in U.S. Pat. No.
5,070,215, and the hydrophilic oxazolone monomers disclosed in U.S.
Pat. No. 4,910,277. The contents of these patents are incorporated
herein by reference. The hydrophilic monomer also can be an anionic
monomer, such as 2-methacryloyloxyethylsulfonate salts. Substituted
anionic hydrophilic monomers, such as from acrylic and methacrylic
acid, can also be utilized wherein the substituted group can be
removed by a facile chemical process. Non-limiting examples of such
substituted anionic hydrophilic monomers include trimethylsilyl
esters of (meth)acrylic acid, which are hydrolyzed to regenerate an
anionic carboxyl group. The hydrophilic monomer also can be a
cationic monomer selected from the group consisting of
3-methacrylamidopropyl-N,N,N-trimethyammonium salts,
2-methacryloyloxyethyl-N,N,N-trimethylammonium salts, and
amine-containing monomers, such as
3-methacrylamidopropyl-N,N-dimethyl amine. Other suitable
hydrophilic monomers will be apparent to one skilled in the
art.
[0029] The hydrophilic monomer block will be sized to provide the
desirable surface coating property of the reactive segmented block
copolymer. The size of the hydrophilic oligomeric or polymeric
block may vary depending upon the substrate to be coated and the
intended use. Therefore the variable n of formula I, II or III can
be between 1 and about 10000, preferably between about 10 and about
1000, and more preferably between about 20 and about 300.
[0030] Atom-transfer radical polymerization (ATRP) can be used to
prepare segmented block copolymers in which the molecular weight of
each of the blocks and the entire polymer can be precisely
controlled. As shown in FIG. 1, atom-transfer radical
polymerization (ATRP) can be used to make a segmented block
copolymer in which there is a block of the chemical binding unit at
one end of the polymer followed by a large hydrophilic block. It
should be understood that the order of addition of the monomer
comprising the chemical binding unit domain and the monomer
comprising the hydrophilic domain is not critical. A large number
of monomers are available for the assembly of polymers (For
example, see FIG. 2). Reversible addition-fragmentation chain
transfer polymerization (RAFT) can also be used to prepare
segmented block copolymers in which the molecular weight of each of
the blocks and the entire polymer can be precisely controlled (see
FIG. 3).
[0031] The reactive segmented block copolymers of the invention
herein are useful in providing coatings for substrates. Non
limiting examples of substrate materials useful with the present
invention are taught in U.S. Pat. No. 5,908,906 to Kunzler et al.;
U.S. Pat. No. 5,714,557 to Kunzler et al.; U.S. Pat. No. 5,710,302
to Kunzler et al.; U.S. Pat. No. 5,708,094 to Lai et al.; U.S. Pat.
No. 5,616,757 to Bambury et al.; U.S. Pat. No. 5,610,252 to Bambury
et al.; U.S. Pat. No. 5,512,205 to Lai; U.S. Pat. No. 5,449,729 to
Lai; U.S. Pat. No. 5,387,662 to Kunzler et al.; U.S. Pat. No.
5,310,779 to Lai and U.S. Pat. No. 6,891,010 to Kunzler et al.;
which patents are incorporated by reference as if set forth at
length herein.
[0032] The present invention contemplates the use of reactive
segmented block copolymers with medical devices including both
"hard" and "soft" contact lenses. As disclosed above, the invention
is applicable to a wide variety of materials. Hydrogels in general
are a well-known class of materials that comprise hydrated,
cross-linked polymeric systems containing water in an equilibrium
state. Silicon containing hydrogens generally have water content
greater than about 5 weight percent and more commonly between about
10 to about 80 weight percent. Such materials are usually prepared
by polymerizing a mixture containing at least one silicon
containing monomer and at least one hydrophilic monomer. Typically,
either the silicon containing monomer or the hydrophilic monomer
functions as a crosslinking agent (a crosslinker being defined as a
monomer having multiple polymerizable functionalities) or a
separate crosslinker may be employed. Applicable silicon containing
monomeric units for use in the formation of silicon containing
hydrogels are well known in the art and numerous examples are
provided in U.S. Pat. Nos. 4,136,250; 4,153,641; 4,740,533;
5,034,461; 5,070,215; 5,260,000; 5,310,779; and 5,358,995.
[0033] Examples of applicable silicon-containing monomeric units
include bulky polysiloxanylalkyl (meth)acrylic monomers. An example
of bulky polysiloxanylalkyl (meth)acrylic monomers are represented
by the following Formula IV:
##STR00003##
wherein: [0034] X denotes --O-- or --NR--; [0035] each R.sub.1
independently denotes hydrogen or methyl; [0036] each R.sub.2
independently denotes a lower alkyl radical, phenyl radical or a
group represented by
##STR00004##
[0036] wherein each R'.sub.2' independently denotes a lower alkyl
or phenyl radical; and h is 1 to 10. Some preferred bulky monomers
are methacryloxypropyl tris(trimethyl-siloxy)silane or
tris(trimethylsiloxy)silylpropyl methacrylate, sometimes referred
to as TRIS.
[0037] Another class of representative silicon-containing monomers
includes silicon containing vinyl carbonate or vinyl carbamate
monomers such as:
1,3-bis[4-vinyloxycarbonyloxy)butyl]tetramethyl-disiloxane;
3-(trimethylsilyl)propyl vinyl carbonate;
3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];
3-[tris(tri-methylsiloxy)silyl]propyl vinyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;
t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl
vinyl carbonate; and trimethylsilylmethyl vinyl carbonate.
[0038] An example of silicon-containing vinyl carbonate or vinyl
carbamate monomers are represented by Formula V:
##STR00005##
wherein:
[0039] Y' denotes --O--, --S-- or --NH--;
[0040] R.sup.Si denotes a silicon containing organic radical;
[0041] R.sub.3 denotes hydrogen or methyl;
[0042] d is 1, 2, 3 or 4; and q is 0 or 1.
[0043] Suitable silicon containing organic radicals R.sup.Si
include the following:
##STR00006##
[0044] wherein:
[0045] R.sub.4 denotes
##STR00007##
[0046] wherein p' is 1 to 6;
[0047] R.sub.5 denotes an alkyl radical or a fluoroalkyl radical
having 1 to 6 carbon atoms;
[0048] e is 1 to 200; n' is 1, 2, 3 or 4; and m' is 0, 1, 2, 3, 4
or 5.
[0049] An example of a particular species within Formula V is
represented by Formula VI.
##STR00008##
[0050] Another class of silicon-containing monomers includes
polyurethane-polysiloxane macromonomers (also sometimes referred to
as prepolymers), which may have hard-soft-hard blocks like
traditional urethane elastomers. They may be end-capped with a
hydrophilic monomer such as HEMA. Examples of such silicon
containing urethanes are disclosed in a variety of publications,
including Lai, Yu-Chin, "The Role of Bulky Polysiloxanylalkyl
Methacryates in Polyurethane-Polysiloxane Hydrogels," Journal of
Applied Polymer Science, Vol. 60, 1193-1199 (1996). PCT Published
Application No. WO 96/31792 discloses examples of such monomers,
which disclosure is hereby incorporated by reference in its
entirety. Further examples of silicon containing urethane monomers
are represented by Formulae VII and VIII:
E(*D*A*D*G).sub.a*D*A*D*E' (VII) ; or
E(*D*G*D*A).sub.a*D*G*D*E' (VIII);
[0051] wherein: [0052] D denotes an alkyl diradical, an alkyl
cycloalkyl diradical, a cycloalkyl diradical, an aryl diradical or
an alkylaryl diradical having 6 to 30 carbon atoms; [0053] G
denotes an alkyl diradical, a cycloalkyl diradical, an alkyl
cycloalkyl diradical, an aryl diradical or an alkylaryl diradical
having 1 to 40 carbon atoms and which may contain ether, thio or
amine linkages in the main chain; [0054] * denotes a urethane or
ureido linkage; [0055] a is at least 1; [0056] A denotes a divalent
polymeric radical of Formula IX:
##STR00009##
[0057] wherein: [0058] each R.sub.s independently denotes an alkyl
or fluoro-substituted alkyl group having 1 to 10 carbon atoms which
may contain ether linkages between carbon atoms; [0059] m' is at
least 1; and [0060] p is a number which provides a moiety weight of
400 to 10,000; [0061] each of E and E' independently denotes a
polymerizable unsaturated organic radical represented by Formula
X:
##STR00010##
[0062] wherein: [0063] R.sub.6 is hydrogen or methyl; [0064]
R.sub.7 is hydrogen, an alkyl radical having 1 to 6 carbon atoms,
or a --CO--Y--R.sub.9 radical wherein Y is --O--, --S-- or --NH--;
[0065] R.sub.8 is a divalent alkylene radical having 1 to 10 carbon
atoms; [0066] R.sub.9 is a alkyl radical having 1 to 12 carbon
atoms; [0067] X denotes --CO-- or --OCO--; [0068] Z denotes --O--
or --NH--; [0069] Ar denotes an aromatic radical having 6 to 30
carbon atoms; [0070] w is 0 to 6; x is 0 or 1; y is 0 or 1; and z
is 0 or 1.
[0071] A more specific example of a silicon containing urethane
monomer is represented by Formula (XI):
##STR00011## [0072] wherein m is at least 1 and is preferably 3 or
4, a is at least 1 and preferably is 1, p is a number which
provides a moiety weight of 400 to 10,000 and is preferably at
least 30, R.sub.10 is a diradical of a diisocyanate after removal
of the isocyanate group, such as the diradical of isophorone
diisocyanate, and each E'' is a group represented by:
##STR00012##
[0073] A preferred silicon containing hydrogel material comprises
(in the bulk monomer mixture that is copolymerized) 5 to 50
percent, preferably 10 to 25 percent, by weight of one or more
silicon containing macromonomers, 5 to 75 percent, preferably 30 to
60 percent, by weight of one or more polysiloxanylalkyl
(meth)acrylic monomers, and 10 to 50 percent, preferably 20 to 40
percent, by weight of a hydrophilic monomer. In general, the
silicon containing macromonomer is a poly(organosiloxane) capped
with an unsaturated group at two or more ends of the molecule. In
addition to the end groups in the above structural formulas, U.S.
Pat. No. 4,153,641 to Deichert et al. discloses additional
unsaturated groups, including acryloxy or methacryloxy.
Fumarate-containing materials such as those taught in U.S. Pat.
Nos. 5,512,205; 5,449,729; and 5,310,779 to Lai are also useful
substrates in accordance with the invention. Preferably, the silane
macromonomer is a silicon-containing vinyl carbonate or vinyl
carbamate or a polyurethane-polysiloxane having one or more
hard-soft-hard blocks and end-capped with a hydrophilic
monomer.
[0074] Suitable hydrophilic monomers form hydrogels, such as
silicon-containing hydrogel materials useful in the present
invention. Examples of useful monomers include amides such as
dimethylacrylamide, dimethylmethacrylamide, cyclic lactams such as
n-vinyl-2-pyrrolidone and poly(alkene glycols) functionalized with
polymerizable groups. Examples of useful functionalized poly(alkene
glycols) include poly(diethylene glycols) of varying chain length
containing monomethacrylate or dimethacrylate end caps. In a
preferred embodiment, the poly(alkene glycol) polymer contains at
least two alkene glycol monomeric units. Still further examples are
the hydrophilic vinyl carbonate or vinyl carbamate monomers
disclosed in U.S. Pat. No. 5,070,215, and the hydrophilic oxazolone
monomers disclosed in U.S. Pat. No. 4,910,277. Other suitable
hydrophilic monomers will be apparent to one skilled in the
art.
Device Forming Additives and Comonomers
[0075] The monomer mix may, further as necessary and within limits
not to impair the purpose and effect of the present invention,
comprise various additives such as antioxidant, coloring agent,
ultraviolet absorber and lubricant.
[0076] The monomer mix may be prepared by using, according to the
end-use and the like of the resulting shaped polymer articles, one
or at least two of the above comonomers and oligomers and, when
occasions demand, one or more crosslinking agents.
[0077] Where the shaped polymer articles are for example medical
products, in particular a contact lens, the monomer mix is suitably
prepared from one or more of the silicon compounds, e.g. siloxanyl
(meth)acrylate, siloxanyl (meth)acrylamide and silicon containing
oligomers, to obtain contact lenses with high oxygen
permeability.
[0078] The monomer mix may include additional constituents such as
crosslinking agents, internal wetting agents, hydrophilic monomeric
units, toughening agents, and other constituents as is well known
in the art.
[0079] Although not required, the monomer mix may include
toughening agents, preferably in quantities of less than about 80
weight percent e.g. from about 5 to about 80 weight percent, and
more typically from about 20 to about 60 weight percent. Examples
of suitable toughening agents are described in U.S. Pat. No.
4,327,203. These agents include cycloalkyl acrylates or
methacrylates, such as: methyl acrylate and methacrylate,
t-butylcyclohexyl methacrylate, isopropylcyclopentyl acrylate,
t-pentylcycloheptyl methacrylate, t-butylcyclohexyl acrylate,
isohexylcyclopentyl acrylate and methylisopentyl cyclooctyl
acrylate. Additional examples of suitable toughening agents are
described in U.S. Pat. No. 4,355,147. This reference describes
polycyclic acrylates or methacrylates such as: isobornyl acrylate
and methacrylate, dicyclopentadienyl acrylate and methacrylate,
adamantyl acrylate and methacrylate, and isopinocamphyl acrylate
and methacrylate. Further examples of toughening agents are
provided in U.S. Pat. No. 5,270,418. This reference describes
branched alkyl hydroxyl cycloalkyl acrylates, methacrylates,
acrylamides and methacrylamides. Representative examples include:
4-t-butyl-2-hydroxycyclohexyl methacrylate (TBE);
4-t-butyl-2-hydroxycyclopentyl methacrylate;
methacryloxyamino-4-t-butyl-2-hydroxycyclohexane;
6-isopentyl-3-hydroxycyclohexyl methacrylate; and
methacryloxyamino-2-isohexyl-5-hydroxycyclopentane.
[0080] In particular regard to contact lenses, the fluorination of
certain monomers used in the formation of silicon containing
hydrogels has been indicated to reduce the accumulation of deposits
on contact lenses made therefrom, as described in U.S. Pat. Nos.
4,954,587, 5,079,319, 5,010,141 and 6,891,010. Moreover, the use of
silicon containing monomers having certain fluorinated side groups,
i.e. --(CF.sub.2)--H, have been found to improve compatibility
between the hydrophilic and silicon containing monomeric units, as
described in U.S. Pat. Nos. 5,387,662 and 5,321,108.
[0081] As stated above, surface structure and composition determine
many of the physical properties and ultimate uses of solid
materials. Characteristics such as wetting, friction, and adhesion
or lubricity are largely influenced by surface characteristics. The
alteration of surface characteristics is of special significance in
biotechnical applications where biocompatibility is of particular
concern. Thus, it is desired to provide a silicon containing
hydrogel contact lens with an optically clear, hydrophilic surface
film that will not only exhibit improved wettability, but which
will generally allow the use of a silicon containing hydrogel
contact lens in the human eye for extended period of time. In the
case of a silicon containing hydrogel lens for extended wear, it
may be further desirable to provide an improved silicon-containing
hydrogel contact lens with an optically clear surface film that
will not only exhibit improved lipid and microbial behavior, but
which will generally allow the use of a silicon-containing hydrogel
contact lens in the human eye for an extended period of time. Such
a surface treated lens would be comfortable to wear in actual use
and allow for the extended wear of the lens without irritation or
other adverse effects to the cornea.
[0082] It may also be desirable to apply these surface enhancing
coatings to implantable medical devices such as intraocular lens
materials to reduce the attachment of lens epithelial cells to the
implanted device and to reduce friction as the intraocular lens
passes through an inserter into the eye.
[0083] The present invention is useful for surface treatment of a
polymeric device. The surface treatment comprises the binding of
reactive segmented block copolymers to the surface of a polymeric
medical device substrate by reacting complementary reactive
functionalities of the reactive segmented block copolymers with
reactive functionalities along the polymeric substrate surface.
[0084] As set forth above, for surface modification of contact
lenses in accordance with the segmented block copolymers of the
present invention, complementary functionality is incorporated
between the surface of the contact lens material (i.e., the
substrate) and the chemical binding unit block of the reactive
segmented block copolymer used as a surface modification treatment
polymer (surface modifying agent). For example, if a surface
modifying agent has epoxide functionality, then the contact lens
material to be treated must have a residue with complementary
functionality that will react with that of the surface modifying
agent. In such a case, the contact lens material could include a
reactive prepolymer such as bis-.alpha.,.omega.-fumaryl butyl
polydimethyl siloxane diacid to react with the surface modifying
agent epoxide functionality. Likewise, if a contact lens is formed
from material having a residue providing epoxide functionality, a
surface modifying agent containing a 2-hydroxyethyl methacrylate
functionality could be used for surface modification in accordance
with the present invention. Such complementary chemical
functionality enables binding to occur between the surface of the
contact lens and the reactive groups of the one or more surface
modifying agent's. This binding between functional groups forms
covalent linkages there between. For example, a contact lens
containing prepolymer having surface hydroxyl functional groups
preferably undergo surface modification using surface modifying
agents containing carboxylic acid functional groups, isocyanate
functional groups or epoxy functional groups. Likewise, a contact
lens having surface carboxylic acid groups preferably undergo
surface modification using surface modifying agents containing
glycidyl methacrylate (GMA) monomer units to provide epoxy
functional groups. The reaction of the contact lens containing
surface reactive functional groups and the reactive surface
modifying agent is conducted under conditions known to those of
skill in the art.
[0085] In the case where reactive groups are not present in the
substrate material, they can be added. For example, by using a
surface activation treatment such as oxygen plasma,
ammonia-butadiene-ammonia (ABA) treatments and
hydrogen-ammonia-butadiene-ammonia (HABA) treatments. Plasma
treatment of substrate materials is known and is described in U.S.
Pat. No. 6,193,369 Valint et al., U.S. Pat. No. 6,213,604 Valint et
al. and U.S. Pat. No. 6,550,915 Grobe, III.
[0086] Methods of coating the substrate include dip coating of the
substrate into a solution containing the surface modifying agent.
The solution containing the surface modifying agent may contain
substantially the surface modifying agent in solvent or may contain
other materials such as cleaning and extracting materials. Other
methods could include spray coating the device with the surface
modifying agent. In order for the covalent bonding reaction to
occur, it may be necessary to use suitable catalysts, for example,
condensation catalyst. Alternatively, the substrate and the other
surface modifying agent may be subjected to autoclave conditions.
In certain embodiments, the substrate and the surface modifying
agent may be autoclaved in the packaging material that will contain
the coated substrate. Once the reaction between the substrate and
the surface modifying agent has occurred, the remaining surface
modifying agent could be substantially removed and packaging
solution be added to the substrate packaging material. Sealing and
other processing steps then proceed as they usually do.
Alternatively, the surface modifying agent could be retained in the
substrate packaging material during storage and shipping of the
substrate device to the end user.
[0087] The reactive segmented block copolymers useful in certain
embodiments of the present invention may be prepared according to
syntheses well known in the art and according to the methods
disclosed in the following examples.
EXAMPLES
Example A
Synthesis of NVP-b-GVC Copolymer
[0088] AIBN (46 mgs; 2.82.times.10.sup.-4 mol) was added to a 100
mL Schlenk flask equipped with a magnetic stirring bar. To the
flask was added 586 mgs (2.82.times.10.sup.-4) of
ethyl-.alpha.-(O-ethylxanthyl)propionate (EEXP) dissolved in a
small amount of dioxane. Dioxane (15 ml) and N-vinylpyrrolidone
(NVP) [15 ml; 0.141 mol] were added to the Schlenk flask, which was
then sealed and purged with N.sub.2 for 30 minutes. The flask was
placed in an oil bath (60.degree. C.) for 23 hours. After cooling
to RT, 20 ml of THF was added to the flask and the reaction was
precipitated into diethyl ether. The precipitate was isolated by
filtration and dried in vacuo yielding 10.53 grams of white solid
(PVP MacroRAFT agent).
[0089] The second binding block (GVC) was added to the PVP
MacroRAFT agent in a second reaction. Two grams of PVP MacroRAFT
agent (approx. 4.0.times.10.sup.-4 mol based on assumption of 5K
mol wt) was added to a 100 mL Schlenk flask along with 4 mL of
1,4-dioxane and a stir bar. 1.136-g (2.82.times.10.sup.-4mol) of
Glycidyl vinyl carbamate (N-vinyl) and 20 mgs of AIBN
(1.22.times.10.sup.-4 mol) were then added to the flask which was
sealed and purged with N2 for 30 minutes. The viscous mixture was
placed in an oil bath (60.degree. C.) for 221/2 hours. The reaction
was cooled to RT and 5 ml of THF was added to the flask before the
product was precipitated into diethyl ether. The precipitate was
filtered and dried in vacuo at 25.degree. C. to yield 2.44 grams of
isolated product. *Note: Glycidyl vinyl carbamate is the product
from the reaction of glycidol with vinyl isocyanate.
[0090] Both the PVP MacroRAFT agent and the block copolymer of NVP
and GVC were characterized by proton NMR (CDCl.sub.3) and GPC and
the data support the incorporation of a GVC block onto the end of
the PVP chain. The GPC shows a shift in the elution peak to shorter
times (higher MW) after the addition of the GVC block. In addition,
the NMR spectra shows peaks for the glycidyl groups present at 2.65
ppm and 2.85 ppm that are not present in the spectra of the PVP
MacroRAFT agent. The integration in the NMR spectrum shows that
there is a mole ratio of PVP:PGVC of approximately 7:1.
Example B
Synthesis of DMA-b-GMA Copolymer
[0091] Weighed 353 mgs (0.97 mmol) of
S-1-Dodecyl-S-(.alpha.,.alpha.'-dimethyl-.alpha.''-acetic
acid)trithiocarbonate and 33 mgs of AIBN into a 50 ml Schlenk
flask. Added 10 ml (97 mmol) of N,N-Dimethylacrylamide (DMA) and 20
ml of tetrahydrofuran (THF) to the flask, sealed flask with a
septum and then purged with argon to deoxygenate for 30 mins.
Placed flask in a 50.degree. C. oil bath for 4.5 hrs. In a separate
container, 2.0 ml (14.66 mmol) of glycidyl methacrylate (GMA) was
bubbled with argon for 30 mins., then added to the flask after 4.5
hrs. *Note: A small aliquot was taken from the flask immediately
before GMA addition and precipitated into diethyl ether. The
reaction was stopped 15 hours after GMA addition (19.5 hrs total
reaction time). The final product was dissolved in THF and
precipitated into diethyl ether.
[0092] Both the first precipitate and the block copolymer of DMA
and GMA were characterized by proton NMR (CDCl3) and GPC. The GPC
shows a shift in the elution peak to shorter times (higher MW)
after the addition of the GMA block. In addition, the NMR spectra
of the block copolymer shows peaks for the glycidyl methacrylate
contributions at 3.7 ppm and 4.3 ppm.
[0093] *Note: This polymerization yields a block copolymer,
PDMA-block-(PGMA-co-PDMA), in which the second block is actually a
statistical copolymerization of the GMA and any remaining DMA that
had not been polymerized at the time of the GMA addition. The
second "block", is therefore compositionally heterogeneous.
However, given the reactivity ratios of this pair of monomers (rDMA
.about.0.5, rGMA .about.2.5, assuming GMA and MMA behave similarly)
the GMA should be preferentially incorporated into the second
"block". A polymerization that yields a statistical
copolymerization or compositionally heterogeneous block as the
second block would also be considered to be a reactive segmented
block copolymer according to the invention herein.
[0094] Additionally, the amount of remaining DMA monomer can be
monitored by GC and the addition of the second monomer can occur
after all the DMA in the reaction is consumed.
Example C
Removal of End Group
[0095] To remove the RAFT end group, 4.0 grams of the copolymer
from example B (DMA-b-GMA) was dissolved in 15 mL of dioxane in a
round bottom flask. To the flask was added 250 microliters of
tris(trimethylsilyl) silane and 65.8 mgs of AIBN. The solution was
sparged with nitrogen for 30 minutes and then heated at 80.degree.
C. for 12 h under a nitrogen blanket. The cooled solution was
precipitated by dropwise addition into diethyl ether. The white
solid was collected by vacuum filtration and vacuum dried at RT.
Cleavage of the trithiocarbonate end group was evidenced by the
loss of yellow color of the product and the disappearance of the
dodecyl resonances in the proton NMR.
Example D
Synthesis of a Matrix of GMA-b-DMA Copolymers where the MW of Each
of the Blocks is Varied
TABLE-US-00004 [0096] MW DMA MW GMA DMA DMA CTR CTR GMA GMA block
block Reaction (mL) (mol) (mgs) (mol) (mL) (mol) (theoretical)
(theoretical) 2748-114 20 0.194 350 0.00097 2.0 0.0146 19,800 2,140
2748-115 20 0.194 350 0.00097 4.0 0.0293 19,800 4,275 2748-116 20
0.194 350 0.00097 8.0 0.0586 19,800 8,550 2748-117 20 0.194 700
0.00194 2.0 0.0146 9,900 1,070 2748-118 20 0.194 700 0.00194 4.0
0.0293 9,900 2,140 2748-119 20 0.194 700 0.00194 8.0 0.0586 9,900
4,275 2748-120 10 0.097 700 0.00194 2.0 0.0146 4,950 1,070 2748-121
10 0.097 700 0.00194 4.0 0.0293 4,950 2,140 2748-122 10 0.097 700
0.00194 8.0 0.0586 4,950 4,275 ~33 mgs of AIBN were added to all of
the reactions Note: All reactions were carried out in a similar
fashion using the amounts shown in the table above. Reaction
2748-114 is described below as an example of the procedure used.
Weighed 350 mgs (0.97 mmol) of S-1-Dodecyl-S-(.alpha.,
.alpha.'-dimethyl-.alpha.''-acetic acid) trithiocarbonate and 33
mgs of AIBN into a 250 ml round bottom flask. Added 20 ml (194
mmol) of N,N-Dimethylacrylamide (DMA) and 60 ml of dioxane to the
flask, sealed flask with a septum and then purged with argon to
deoxygenate for 30 mins. Placed flask in an oil bath (50.degree.
C.) for 6.0 hrs. In a separate container, 2.0 ml (14.66 mmol) of
glycidyl methacrylate (GMA) was bubbled with argon for 30 mins.,
then added to the flask after 6.0 hrs. Note: A small aliquot was
taken from the flask immediately before GMA addition and
precipitated into diethyl ether. The reaction was stopped 15 hours
after GMA addition (19.5 hrs total reaction time). The final
product was precipitated out of the reaction mixture into diethyl
ether.
[0097] Both the first precipitate and the block copolymer of DMA
and GMA were characterized by proton NMR (CDCl3) and GPC. The GPC
shows a shift in the elution peak to shorter times (higher MW)
after the addition of the GMA block. In addition, the NMR spectra
of the block copolymer shows peaks for the glycidol methacrylate
contributions at 3.7 ppm and 4.3 ppm. GPC data for these polymers
using DMF as an eluent are shown below, using both PMMA standards
and PVP standards as calibrants. Although the trends in MW are the
same, PMMA standards show MW's much closer to the theoretically
expected value for polyDMA.
TABLE-US-00005 PMMA Standards PVP Standards Sample Mw Mn Mw Mn
2748-114 20,270 15,320 432,500 207,100 2748-115 -- -- 534,200
219,500 2748-116 -- -- 681,500 282,000 2748-117 8,950 6,430 147,800
71,700 2748-118 -- -- 182,400 74,100 2748-119 -- -- 245,900 72,300
2748-120 4,000 2,540 48,600 16,100 2748-121 -- -- 70,100 15,000
2748-122 -- -- 145,100 20.0
Example E
Synthesis of a Random Copolymers of DMA-r-GMA as Comparative
Examples Using Conventional Free-Radical Polymerization
TABLE-US-00006 [0098] Sample DMA (mL) DMA (mol) GMA (mL) GMA (mol)
AIBN (mgs) Mw Mn 2748-123A 20 0.194 2.94 0.0215 46 122,900 25,200
2748-123B 20 0.194 4.68 0.0342 50 129,800 33,000 Note: GPC data is
reported versus PMMA standards with DMF as the eluent
[0099] Both of the reactions were carried out in a similar fashion
using the amounts shown in the table above. Reaction 2748-1 23A is
described below as an example of the procedure used. Added 20 ml of
DMA and 2.94 ml of GMA to a 0.5 L round bottom flask. Added 46 mgs
of AIBN and 200 ml of dioxane before bubbling argon through the
reaction mixture for 1 hour to remove any dissolved oxygen. Round
bottom flask was then lowered into an oil bath set at 64.degree. C.
and the polymerization was allowed to proceed for 48 hours. The
flask was then removed from the oil bath and the product was
precipitated by dropwise addition into diethyl ether. The
precipitated polymer was isolated by filtration and dried at RT in
a vacuum oven.
[0100] The random copolymers of DMA and GMA were characterized by
proton NMR (CDCl3) and GPC. The GPC data with DMF as an eluent are
shown in the table above and the MW of both of these samples was
considerably larger than their RAFT polymerized counterparts
detailed in example D. In addition, the NMR spectra of the random
copolymers showed peaks for the glycidol methacrylate contributions
at 3.7 ppm and 4.3 ppm.
[0101] The molar ratios of DMA to GMA in the randomly polymerized
samples were chosen to approximate the molar ratios of those
produced by RAFT polymerization in example D. For the random
samples the two polymers were DMA(90)-r-GMA(10) [2748-123A] and
DMA(85)-r-GMA(15) [2748-123B]. *Mole percent of each monomer given
in parenthesis.
Example F
Coating of a Silicone Hydrogel Formulation
[0102] Contact lenses of a cationic silicone hydrogel formulation
were prepared comprising the two silicone containing monomers shown
below (M2D39+ and M1-MCR-C12); N-vinyl-2-pyrrolidone ("NVP");
tris(trimethylsiloxy)silylpropyl methacrylate ("TRIS");
2-hydroxyethyl methacrylate ("HEMA"), a UV blocking monomer (SA
monomer); and AIBN. The "reactive handle" present in this substrate
was the --OH group of HEMA which was present at 18.6 parts in the
formulation. The lens formulation was thermally cured between two
polypropylene molds at 110.degree. C. for 4 hours, removed from the
mold and extracted in IPA for 4 hours before transferring to
deionized water.
##STR00013##
[0103] Sample 2748-118 from example D; and samples 2748-123A and
2748-123B from example E were used to prepare coating solutions. In
a typical coating experiment, the lenses prepared above were placed
in a polypropylene (PP) blister containing 3.8-mL of a 250 ppm
(w/v) solution of subject polymer dissolved in pH=7.2 Trizma
buffer. A control lot with no coating polymer was also produced.
The lens blisters were sealed and autoclaved at 121.degree. C. for
30-min. After the autoclave, the lenses were removed from the
blister packages and rinsed for 24 hours in purified water and the
surface was analyzed using X-ray photoelectron spectroscopy (XPS)
to deter-mine the elemental composition of the surface and static
contact angle. The surface data is shown in the table below.
TABLE-US-00007 XPS Data Contact Sample C1s N1s O1s Si2p Angle
Static Control 66.5 (0.5) 4.0 (0.6) 21.1 (1.0) 8.3 (0.6) 117.3
(0.6) 2748-118 (block) 68.9 (1.1) 6.9 (0.6) 20.3 (0.6) 2.9 (1.2)
86.6 (11.0) 2748-123A (random) 66.0 (0.7) 3.9 (0.4) 21.5 (0.5) 8.5
(0.4) 115.4 (1.6) 2748-123B (random) 67.0 (0.9) 5.4 (0.8) 20.9
(0.7) 6.5 (0.8) 111.3 (5.9)
[0104] As can be seen from the XPS data, the reactive segmented
block copolymer 2748-118 leads to the largest reduction in silicon
(Si2p) at the surface of the lens and the largest increase in
nitrogen (N1s). This is indicative of this GMA-b-DMA reactive
segmented block copolymer being efficient at reacting with the lens
surface and coating the lens substrate. In addition the static
contact angle for the block copolymer 2748-118 is lower than the
control and either of the random copolymers, which also suggest
that there is more of the hydrophilic reactive segmented block
copolymer bound to the lens.
[0105] XPS data was collected on a Physical Electronics Quantera
SXM (Scanning X-ray Microprobe) Sample acquisitions are rastered
over a 1400 micron.times.100 micron analysis spot. Dual beam
neutralization (ions and electrons) was used during all analysis.
The instrument base pressure was 5.times.10.sup.-10 torr and during
operation the pressure was less than or equal to 1.times.10.sup.-7
torr. Each specimen was analyzed utilizing a low-resolution survey
spectra (0-1100 eV) to identify the elements present on the sample
surface. Quantification of elemental compositions was completed by
integration of the photoelectron peak areas. Analyzer transmission,
photoelectron cross-sections and source angle correction were taken
into consideration in order to give accurate atomic concentration
values.
[0106] Three lenses from each lot were placed in glass vials
containing HPLC grade water, and were placed on a shaker for 24
hours to rinse away unbound coating polymer. After that time the
samples were placed in sterile Petri dishes and rinsed in HPLC
grade water for 15 minutes. The lenses were then sliced into
quarters using a clean sterile scalpel, clean tweezers and silicon
free latex gloves. The quarters for XPS analysis were mounted on
clean metal platens, with three posterior and three anterior sides
facing up, using clean metal masks. The samples were placed in a
nitrogen dry box overnight before introduction into the
spectrometer.
[0107] For contact angle analysis, samples were mounted on a clean
glass slide and dried overnight in a nitrogen dry box. Contact
angles were measured on the dehydrated lenses at two points on each
sample. The instrument used for measurement was an AST Products
Video Contact Angle System (VCA) 2500XE. This instrument utilizes a
low-power microscope that produces a sharply defined image of the
water drop, which is captured immediately on the computer screen.
HPLC water was drawn into the VCA system microsyringe, and a 0.6
.mu.l drop is dispensed from the syringe onto the sample. The
contact angle is calculated by placing three to five markers along
the circumference of the drop. The software calculates a curve
representing the circumference of the drop and the contact angle is
recorded. Both a right and left contact angle are reported for each
measurement. Reported in the table above is the average of
both.
Example G
Synthesis of DMA-b-GMA Copolymer with a Difunctional
Trithiocarbonate
[0108] Weigh 353 mg of
S,S'-bis(.alpha.,.alpha.'-dimethyl-.alpha.''acetic
acid)trithiocarbonate and 33 mg of AIBN into a 50 ml Schlenk flask.
Add 10 ml of N,N-Dimethylacrylamide (DMA) and 20 ml of
tetrahydrofuran (THF) to the flask. Seal flask with a septum and
purge with argon to deoxygenate for 30 mins. Place flask in a
50.degree. C. oil bath for 4.5 hrs. In a separate container, 2.0 ml
of glycidyl methacrylate (GMA) is bubbled with argon for 30 mins.,
then added to the flask after 4.5 hrs. Stop reaction 15 hours after
GMA addition and precipitate final product into diethyl ether.
[0109] While there is shown and described herein certain specific
structures and compositions of the present invention, it will be
manifest to those skilled in the art that various modifications may
be made without departing from the spirit and scope of the
underlying inventive concept and that the same is not limited to
particular structures herein shown and described except insofar as
indicated by the scope of the appended claims the scope of which is
properly understood in view of this specification.
* * * * *