U.S. patent application number 12/335794 was filed with the patent office on 2009-07-02 for coating solutions comprising surface active segmented block copolymers.
Invention is credited to Jay F. Kunzler, Jeffrey G. Linhardt, Devon A. Shipp.
Application Number | 20090169716 12/335794 |
Document ID | / |
Family ID | 40797822 |
Filed Date | 2009-07-02 |
United States Patent
Application |
20090169716 |
Kind Code |
A1 |
Linhardt; Jeffrey G. ; et
al. |
July 2, 2009 |
COATING SOLUTIONS COMPRISING SURFACE ACTIVE SEGMENTED BLOCK
COPOLYMERS
Abstract
This invention is directed toward surface treatment of a device.
The surface treatment comprises the placing of surface active
segmented block copolymers to the surface of the substrate. The
present invention is also directed to a surface modified medical
device, examples of which include contact lenses, intraocular
lenses, vascular stents, phakic intraocular lenses, aphakic
intraocular lenses, corneal implants, catheters, implants, and the
like, comprising a surface made by such a method.
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.: |
12/335794 |
Filed: |
December 16, 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: |
427/2.25 ;
351/159.33; 427/2.1; 427/2.24 |
Current CPC
Class: |
A61L 27/34 20130101;
C08F 130/08 20130101; C08J 7/056 20200101; C08F 2438/03 20130101;
C08F 293/005 20130101; G02B 1/043 20130101; Y10T 428/31536
20150401; C08J 2383/00 20130101; A61L 31/10 20130101; C08F 230/00
20130101; Y10T 428/31663 20150401; A61M 25/0045 20130101; C08J
2343/04 20130101 |
Class at
Publication: |
427/2.25 ;
427/2.1; 427/2.24; 351/160.R; 351/160.H |
International
Class: |
B05D 1/00 20060101
B05D001/00; G02C 7/04 20060101 G02C007/04 |
Claims
1. A method of forming a surface modified medical device, the
method comprising: providing a medical device having at least one
surface; providing a surface modifying agent comprising a surface
active segmented block copolymer; and contacting the at least one
surface of the medical device with the surface modifying agent to
form a surface modified medical device.
2. The method of claim 1 wherein the medical device comprises a
silicon containing monomer.
3. The method of claim 2 wherein the silicon containing monomer
comprises a silicon containing monomer selected from the group
consisting of silicon containing vinyl carbonates, silicon
containing vinyl carbamates, polyurethane-polysiloxanes having one
or more hard-soft-hard blocks and end-capped with a hydrophilic
monomer, fumarate containing silicon containing monomers,
poly(organosiloxanes) capped with an unsaturated group at two or
more ends of the molecule, polyurethane-polysiloxane macromonomers
and mixtures thereof.
4. The method of claim 1 wherein the medical device comprises
hydrogel materials.
5. The method of claim 2 wherein the medical device comprises
silicon containing hydrogel materials.
6. The method of claim 1 wherein the medical device comprises vinyl
functionalized polydimethylsiloxanes copolymerized with hydrophilic
monomers.
7. The method of claim 1 wherein the medical device comprises a
fluorinated monomer.
8. The method of claim 7 wherein the fluorinated monomer is
selected from the group consisting of methacrylate functionalized
fluorinated polyethylene oxides, fluoroalkylmethacrylates, and
mixtures thereof.
9. The method of claim 1 wherein the medical device is selected
from the group consisting of heart valves, intraocular lenses,
intraocular lens inserter, contact lenses, intrauterine devices,
vessel substitutes, artificial ureters, vascular stents, phakic
intraocular lenses, aphakic intraocular lenses, corneal implants,
catheters, implants, endoscopic instruments, and artificial breast
tissue.
10. The method of claim 9 wherein the medical device formed is a
soft contact lens.
11. The method of claim 10 wherein the medical device is a silicon
containing hydrogel contact lens material.
12. The method of claim 1 wherein the reactive segmented block
copolymer has 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 hydrophobic 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.
13. The method of claim 1 wherein the reactive segmented block
copolymer has 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 hydrophobic 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
fragment of the chain transfer agent or a derivatized reaction
product.
14. The method of claim 1 wherein the interactive segmented block
copolymer has 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 hydrophobic 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.
15. The method of claim 1, wherein the hydrophobic unit of the
surface active segmented block copolymer comprises a monomer
selected from the group consisting of alkyl acrylates, hexyl
methacrylate, lauryl methacrylate, fluoroacrylates,
octofluoropentamethacrylate,
3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate,
polysiloxanylalkyl(meth)acrylic monomers, M1-MCR-C12,
methacryloxypropyl tris(trimethyl-siloxy)silane,
tris(trimethylsiloxy)silylpropyl methacrylate,
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, dodecyl
methacrylate, hexyl vinyl carbamate, hexyl vinyl carbonate,
octafluoropentamethacrylate, octafluoropenta vinyl carbamate, and
mixtures thereof.
16. The method of claim 1, wherein the reactive segmented block
copolymer comprises a hydrophilic unit monomer 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.
17. The method of claim 1, wherein the surface active segmented
block copolymer has a hydrophobic unit comprises between 1 and
about 1,000 units.
18. The method of claim 1, wherein the surface active segmented
block copolymer has a hydrophobic unit comprises between 1 and
about 100 units.
19. The method of claim 1, wherein the surface active segmented
block copolymer has a hydrophobic unit comprising between 1 and
about 30 units.
20. The method of claim 1, wherein the surface active segmented
block copolymer has a hydrophilic block comprising between 1 and
about 10,000 units.
21. The method of claim 1, wherein the surface active segmented
block copolymer has a hydrophilic block comprising between about 10
and about 1,000 units.
22. The method of claim 1, wherein the surface active segmented
block copolymer has a hydrophilic block comprising between about 20
and about 300 units.
23. A surface modified medical device comprising: a medical device;
and a surface active segmented block copolymer comprising a
hydrophobic unit block comprising vinylically unsaturated
polymerizable monomers and a hydrophilic block comprising
vinylically unsaturated polymerizable monomers applied to the
surface of the medical device.
24. The surface modified medical device of claim 23 wherein the
medical device is a contact lens.
25. The surface modified medical device of claim 24 wherein the
medical device is a hydrophilic contact lens.
26. The surface modified medical device of claim 24 wherein the
medical device is a hydrogel contact lens.
27. The method of claim 12 wherein the hydrophobic unit block
comprises vinylically unsaturated polymerizable monomers and the
hydrophilic block comprises vinylically unsaturated polymerizable
monomers.
28. The method of claim 13 wherein the hydrophobic unit block
comprises vinylically unsaturated polymerizable monomers and the
hydrophilic block comprises vinylically unsaturated polymerizable
monomers.
29. The method of claim 14 wherein the hydrophobic unit block
comprises vinylically unsaturated polymerizable monomers and the
hydrophilic block comprises vinylically unsaturated polymerizable
monomers.
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 coating solutions comprising 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 a
number of 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. Surface active segmented block copolymers
show good surface properties when associated with substrates.
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 surface active 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).
[0009] There are a number of commercially available block copolymer
surfactants that can function as antifoaming agents, wetting
agents, dispersants, thickeners, and emulsifiers. One such
surfactant class is the Pluronic.RTM. and Tetronic.RTM. block
copolymers based on ethylene oxide and propylene oxide, available
from BASF. Another class of surfactants is the Silwet.RTM. and
Silsoft.RTM. block copolymers based on ethylene oxide and siloxane
blocks, available from GE silicones. These block copolymers and a
variety of others rely on ring opening polymerization methods to
produce the blocks.
[0010] With the advent and rapid growth of RAFT polymerization in
the late 1990's, block copolymers can now be prepared from a wide
variety of vinyl based monomers. This opens up the toolbox for
polymer chemists to synthesize countless number of block copolymer
compositions. In addition, for the construction of surfactants
there is a lot of chemical diversity in the selection of both the
hydrophobic moieties and the hydrophilic moieties.
[0011] Surfactants or "surface active agents" lower the surface
tension of water or other liquids and concentrate at the surface of
the liquid. Surfactants have a common structural feature in which
one portion of the surfactant molecule is highly polar or even
ionic (hydrophilic or water loving) and the other portion is
largely non-polar (hydrophobic or water fearing). The relationship
of these two structural parts of the molecule with respect to each
other controls the properties of the surfactant.
SUMMARY
[0012] This particular invention is related to the synthesis and
preparation of specifically tailored block copolymer surfactants
where both the lengths of the individual blocks, the chemical
composition, and the sequence distribution are carefully controlled
and the affinity of these surfactants for specific substrates can
be guided by the "like prefers like" principle. For example,
fluorocarbons interact with higher affinity to other
fluorine-containing materials, as well as silicone containing
blocks will interact with higher affinity to silicone containing
materials. Therefore in one embodiment of this invention, a block
copolymer surfactant is prepared via RAFT polymerization that
contains a hydrophilic block (NVP or DMA), and a fluorine
containing hydrophobic block (perfluoroacrylate), where the
surfactant is used to treat a fluorine containing substrate (i.e.
Teflon or a fluoroelastomer). In another embodiment, a block
copolymer surfactant is prepared via RAFT polymerization that
contains a hydrophilic block (NVP or DMA), and a silicone
containing hydrophobic block (TRIS-VC or M1-MCR-C12), where the
surfactant is used to treat a silicone containing substrate (i.e.
silicone hydrogel or a silicone elastomer).
##STR00001##
[0013] In still another embodiment of this invention, a block
copolymer surfactant is prepared via RAFT polymerization that
contains a hydrophilic block (NVP or DMA), and a hydrocarbon
containing hydrophobic block (Hexyl methacrylate or lauryl
methacrylate), where the surfactant is used to treat a hydrocarbon
based substrate (i.e. polyethylene or polypropylene). Disclosed in
certain preferred embodiments herein is a method of forming a
surface modified medical device, the method comprising providing a
medical device having at least one surface; providing a surface
modifying agent comprising a surface active segmented block
copolymer; and contacting the at least one surface of the medical
device with the surface modifying agent to form a surface modified
medical device.
[0014] Also disclosed herein is a surface modified medical device
comprising a medical device and a surface active segmented block
copolymer comprising a hydrophobic unit block comprising
vinylically unsaturated polymerizable monomers and a hydrophilic
block comprising vinylically unsaturated polymerizable monomers
applied to the surface of the medical device.
[0015] Further in accordance with the present disclosure, the
invention relates generally to coating solutions comprising surface
active segmented block copolymers for forming coatings in the
manufacture of medical devices. Examples of suitable devices
include of heart valves, intraocular lenses, intraocular lens
inserter, contact lenses, intrauterine devices, vessel substitutes,
artificial ureters, vascular stents, phakic intraocular lenses,
aphakic intraocular lenses, corneal implants, catheters, implants,
endoscopic instruments, artificial breast tissue and the like.
[0016] Surface active 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 hydrophobic 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.
[0017] Surface active 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 hydrophobic 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.
[0018] Surface active 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 hydrophobic 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 group.
[0019] For each of the polymers of generic formula I, II and III
the order of the block units is not critical and the surface active
segmented block copolymer can contain more than two blocks.
Therefore the surface active 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:
-(A).sub.m-(B).sub.n-- (1)
--(B).sub.n-(A).sub.m- (2)
-(A).sub.m-(B).sub.n-(A)m- (3)
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] 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 hydrophobic unit at one
end of the polymer followed by a large hydrophilic block;
[0021] FIG. 2 is the structural formula of various monomers which
may be used to provide the hydrophobic unit of the segmented block
copolymers of the invention herein;
[0022] FIG. 3 is a reaction schematic showing how RAFT
polymerization can be used to polymerize block copolymers with
surface active domains.
DETAILED DESCRIPTION
[0023] The present invention relates generally to coating solutions
comprising surface active segmented block copolymers. Compositions
comprising the surface active segmented block copolymers are useful
in providing surface bound coatings in the manufacture of medical
devices. In preferred embodiments, the present invention relates to
medical devices surface coated with surface active segmented block
copolymers. It should be understood that the term "surface" as used
to describe surface coating 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. The
surface active 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.
[0024] Therefore, disclosed in certain preferred embodiments herein
is a method of forming a surface modified medical device, the
method comprising providing a medical device having at least one
surface; providing a surface modifying agent comprising a surface
active segmented block copolymer; and contacting the at least one
surface of the medical device with the surface modifying agent to
form a surface modified medical device.
[0025] Also disclosed herein is a surface modified medical device
comprising a medical device; and a surface active segmented block
copolymer comprising a hydrophobic unit block and a hydrophilic
block applied to the surface of the medical device.
[0026] Further in accordance with the present disclosure, the
invention relates generally to coating solutions comprising surface
active segmented block copolymers for forming coatings in the
manufacture of medical devices. Examples of suitable devices
include of heart valves, intraocular lenses, intraocular lens
inserter, contact lenses, intrauterine devices, vessel substitutes,
artificial ureters, vascular stents, phakic intraocular lenses,
aphakic intraocular lenses, corneal implants, catheters, implants,
endoscopic instruments, artificial breast tissue and the like.
[0027] Surface active 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 hydrophobic 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.
[0028] Surface active 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 hydrophobic 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 with the proviso that when A is an
ionic block, B will be a nonionic block. 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.
[0029] Surface active 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 hydrophobic 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.
[0030] For each of the polymers of generic formula I, II and III
the order of the block units is not critical and the surface active
segmented block copolymer can contain more than two blocks.
Therefore the surface active 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:
-(A).sub.m-(B).sub.n-- (1)
--(B).sub.n-(A).sub.m- (2)
-(A).sub.m-(B).sub.n-(A).sub.m- (3)
[0031] The present invention provides materials useful for surface
modifying contact lenses and like medical devices through the use
of surface active 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 method
is suitable for surface modification of other medical devices such
as phakic and aphakic intraocular lenses and corneal implants as
well as contact lenses. The preferred surface active segmented
block copolymers in the present invention are selected based on the
polymeric material to be coated.
[0032] The surface active segmented block copolymer comprises a
hydrophobic unit block. The hydrophobic unit block can be made of
vinylically unsaturated polymerizable monomers. Examples of
hydrophobic vinylically unsaturated polymerizable monomers would
include alkyl acrylates such as hexyl methacrylate and lauryl
methacrylate, fluoroacrylates such as octofluoropentamethacrylate
and 3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate (TDFM)
and polysiloxanylalkyl(meth)acrylic monomers such as TRIS-VC and
M1-MCR-C12. The hydrophobic unit block can be varied and is
selected based upon the intended use of the surface active
segmented block copolymers. That is, the hydrophobic unit block of
the surface active segmented block copolymers is selected to
provide a composition that is complementary with the surface of the
device.
[0033] Selection of the hydrophobic unit monomer of the block
copolymer is determined by the surface of the device. For example,
if the surface active molecule on the surface of the device
contains perfluorinated hydrocarbons, a monomer containing
fluoroalkyl substituents (i.e. octafluoropentyl methacrylate) can
be a hydrophobic unit monomer of the surface active segmented block
copolymer. If the surface active molecule on the surface of the
device contains siloxane functionality, silicone containing
monomers (i.e. TRIS-methacrylate or TRIS-VC) can be a hydrophobic
unit monomer of the surface active segmented block copolymer. A
wide variety of suitable combinations of functional group
containing monomers of the hydrophobic unit complementary to the
surface of the device will be apparent to those of ordinary skill
in the art.
[0034] Generic structures of hydrophobic units would include the
following:
##STR00002##
wherein R can consist of alkyl, fluoroalkyl, siloxy, or branched
silicone.
[0035] Non-limiting examples would include methacryloxypropyl
tris(trimethylsiloxy)silane or tris(trimethylsiloxy)silylpropyl
methacrylate, 3-(trimethylsilyl)propyl vinyl carbonate;
3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];
3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate; hexyl
methacrylate, dodecyl methacrylate, lauryl methacrylate, hexyl
vinyl carbamate, hexyl vinyl carbonate,
octafluoropentamethacrylate, and octafluoropenta vinyl
carbamate.
[0036] The hydrophobic unit block of the surface active segmented
block copolymers is oligomeric or polymeric and is sized to provide
suitable association with 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.
[0037] In addition to the hydrophobic unit, the surface active
segmented block copolymers of the invention herein will also
contain hydrophilic domain(s) showing good surface properties when
the block copolymer is coated onto the substrates. The hydrophilic
domain(s) can be made of vinylically unsaturated polymerizable
monomers such as, HEMA, glycerol 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.
[0038] The hydrophilic monomer block will be sized to provide the
desirable surface coating property of the surface active 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.
[0039] 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 surface active
segmented block copolymer in which there is a block of the
hydrophobic 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 hydrophobic 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).
[0040] The surface active segmented block copolymers of the
invention herein are useful in providing coatings for substrates.
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.
[0041] The present invention contemplates the use of surface active
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 hydrogels 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.
[0042] 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: [0043] X denotes --O-- or --NR--; [0044] each R.sub.1
independently denotes hydrogen or methyl; [0045] each R.sub.2
independently denotes a lower alkyl radical, phenyl radical or a
group represented by
##STR00004##
[0045] 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.
[0046] 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.
[0047] An example of silicon-containing vinyl carbonate or vinyl
carbamate monomers are represented by Formula V:
##STR00005##
wherein:
[0048] Y' denotes --O--, --S-- or --NH--;
[0049] R.sup.Si denotes a silicon containing organic radical;
[0050] R.sub.3 denotes hydrogen or methyl;
[0051] d is 1, 2, 3 or 4; and q is 0 or 1.
[0052] Suitable silicon containing organic radicals R.sup.Si
include the following:
##STR00006##
wherein:
[0053] R.sub.4 denotes
##STR00007##
wherein p' is 1 to 6;
[0054] R.sub.5 denotes an alkyl radical or a fluoroalkyl radical
having 1 to 6 carbon atoms;
[0055] e is 1 to 200; n' is 1, 2, 3 or 4; and m' is 0, 1, 2, 3, 4
or 5.
[0056] An example of a particular species within Formula V is
represented by Formula VI.
##STR00008##
[0057] 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
Methacrylates 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'; or (VII)
E(*D*G*D*A).sub.a*D*G*D*E'; (VIII)
wherein:
[0058] 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;
[0059] 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;
[0060] denotes a urethane or ureido linkage;
[0061] a is at least 1;
[0062] A denotes a divalent polymeric radical of Formula IX:
##STR00009##
wherein: [0063] 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; [0064] m' is at
least 1; and [0065] p is a number which provides a moiety weight of
400 to 10,000; [0066] each of E and E' independently denotes a
polymerizable unsaturated organic radical represented by Formula
X:
##STR00010##
[0066] wherein:
[0067] R.sub.6 is hydrogen or methyl;
[0068] 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--;
[0069] R.sub.8 is a divalent alkylene radical having 1 to 10 carbon
atoms;
[0070] R.sub.9 is a alkyl radical having 1 to 12 carbon atoms;
[0071] X denotes --CO-- or --OCO--;
[0072] Z denotes --O-- or --NH--;
[0073] Ar denotes an aromatic radical having 6 to 30 carbon
atoms;
[0074] w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.
[0075] A more specific example of a silicon containing urethane
monomer is represented by Formula (XI):
##STR00011##
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##
[0076] 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.
[0077] 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
[0078] 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.
[0079] 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.
[0080] 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.
[0081] 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.
[0082] 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.
[0083] 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.
[0084] 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 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.
[0085] It also may 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. It may also be desirable
to apply these surface enhancing coatings to surgical instruments
such as intraocular lens inserters and endoscopic instruments.
[0086] Methods of coating the substrate would 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. 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 contact between the substrate and
the surface modifying agent has occurred, the remaining surface
modifying agent could be substantially removed and packaging
solution would be added to the substrate packaging material.
Sealing and other processing steps would 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] A general method of coating is now described. Medical
devices, such as commercial SofLens.sub.59.TM. contact lenses, are
removed from the packaging and soaked in purified water for at
least 15 minutes prior to being placed in polymer solution. It
should be recognized by persons skilled in the art that the
quantities of a solution disclosed herein may be adjusted under
specific circumstances to accommodate the size of the medical
device. Glass vials are labeled and filled with about 4 ml of a
polymer solution, and a lens is placed in each vial. When two
polymer solutions are used for coating, they are mixed together
immediately prior to placing in the vials. The vials are capped
with silicone stoppers and crimped aluminum caps, then placed in an
autoclave for one 30-minute cycle. The treated lenses are allowed
to cool for a minimum of 3 hours, then removed from the vials and
rinsed at least three times with deionized water. The rinsed lenses
are then placed into new vials containing 4 ml of borate buffered
saline (phosphate for samples undergoing bacterial adhesion
testing) and autoclaved for one 30-minute cycle for
sterilization.
[0088] Other types of contact lenses, such as those comprising
other hydrogel materials can be treated with coating polymers, as
disclosed above. In one embodiment, PureVision.TM. contact lenses
comprising Balafilcon A hydrogel material, disclosed in U.S. Pat.
No. 5,260,000, which is incorporated herein by reference, are
surface-treated with a coating polymer as disclosed above.
(PureVision.TM. contact lenses are available from Bausch and Lomb
Incorporated, Rochester, N.Y.) In one aspect, PureVision.TM.
contact lenses are first treated with a plasma discharge generated
in a chamber containing air. A packaging solution for surface
treatment comprised segmented block poly(TRIS-b-DMA) is added to a
blister package before the lens is placed in and sealed around the
perimeter of the receptacle with lidstock, The blister containing
the lens is then autoclaved for one 30-minute cycle for
sterilization.
[0089] In another method, a fluoro-silicone hydrogel contact lenses
are packaged in a container that includes a receptacle portion to
hold the contact lens and a sterile packaging solution comprising a
segmented block poly(OFPMA-b-DMA). Examples of the container are
conventional contact lens blister packages. This receptacle,
containing the contact lens immersed in the solution, is
hermetically sealed, for example, by sealing lidstock on the
package over the receptacle. For example, the lidstock is sealed
around a perimeter of the receptacle.
[0090] The solution and the contact lens are sterilized while
sealed in the package receptacle. Examples of sterilization
techniques include subjecting the solution and the contact lens to
thermal energy, microwave radiation, gamma radiation or ultraviolet
radiation. A specific example involves heating the solution and the
contact lens, while sealed in the package container, to a
temperature of at least 100.degree. C., more preferably at least
120.degree. C., such as by autoclaving.
[0091] The packaging solution is an aqueous solution that includes
the surface active segmented block copolymer, preferably in an
amount of 0.02 to 5.0 weight percent, based on total weight of the
packaging solution. The specific amount of surface active segmented
block copolymer will vary depending on the substrate and the
copolymer, but generally, the surface active segmented block
copolymer will be present in an amount within this range.
[0092] The packaging solutions preferably have a pH of about 6.0 to
8.0, more preferably about 6.5 to 7.8, and most preferably 6.7 to
7.7. Suitable buffers include monoethanolamine, diethanolamine,
triethanolamine, tromethamine (tris(hydroxymethyl)aminomethane,
Tris), Bis-Tris, Bis-Tris Propane, borate, citrate, phosphate,
bicarbonate, amino acids, and mixtures thereof. Examples of
specific buffering agents include boric acid, sodium borate,
potassium citrate, citric acid, Bis-Tris, Bis-Tris Propane, and
sodium bicarbonate. When present, buffers will generally be used in
amounts ranging from about 0.05 to 2.5 percent by weight, and
preferably from 0.1 to 1.5 percent by weight.
[0093] The packaging solutions may further include a tonicity
adjusting agent, optionally in the form of a buffering agent, for
providing an isotonic or near-isotonic solution having an
osmolality of about 200 to 400 mOsm/kg, more preferably about 250
to 350 mOsm/kg. Examples of suitable tonicity adjusting agents
include sodium and potassium chloride, dextrose, glycerin, calcium
and magnesium chloride. When present, these agents will generally
be used in amounts ranging from about 0.01 to 2.5 weight percent
and preferably from about 0.2 to about 1.5 weight percent.
[0094] Optionally, the packaging solutions may include an
antimicrobial agent, but it is preferred that the solutions lack
such an agent.
[0095] The surface active 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. Surface modification
of contact lenses using one or more surface modifying agents in
accordance with the present invention is described in still greater
detail in the examples that follow.
EXAMPLES
Example A
Synthesis of NVP-b-LMA Copolymer
[0096] To a 100-mL 2-neck round bottom flask equipped with a
magnetic stir bar, 2 septa and an SS sparging needle was added 44
mg of AIBN, 10.0-g (0.090 mol) of N-vinylpyrrolidone (NVP), 0.20-g
(0.00090 mol) of ethyl-.alpha.-(O-ethylxanthyl) propionate (EEXP)
and 20-mL of 1,4-dioxane. The solution was sparged with nitrogen
for 30-min. at RT before heating the flask in an oil bath to
60.degree. C. The solution was sparged throughout the entire course
of the polymerization. After 6 hours at 60.degree. C., a 1 mL
aliquot was removed from the flask and precipitated in 50 mL of
ethyl ether. A quantity of lauryl methacrylate (LMA) (2.64-mL,
0.0090 mol) was then added to the flask in one portion via pipette.
The solution was maintained at 60.degree. C. overnight. The now
hazy solution was cooled to RT and was added dropwise into 2.5-L of
stirred ethyl ether. The precipitate was isolated by filtration and
dried in vacuo at RT affording 6.08-g (49%) of white solid. The
6-hour aliquot was isolated in similar fashion.
[0097] The block copolymer product was characterized by proton NMR
(CDC13) and GPC. Resonances attributable to the alkyl protons of
LMA were observed at approximately 0.8 and 1.25 ppm (not present in
spectrum of the PVP aliquot). GPC was performed using a PLgel
RESIpore column and DMF+1.0 M LiBr as solvent with calibration
using PVP standards. Mn for the PVP aliquot was determined to be
11,650 Daltons (target=11,340 Daltons) with a polydispersity of
1.44. Mn for the block copolymer was determined to be 18,650
Daltons (target=13,900 Daltons) with a polydispersity of 1.63.
Example B
Synthesis of NVP-b-TRIS-VC (Two Step)
[0098] AIBN (23.2 mgs; 1.41.times.10.sup.-4 mol) was added to a 100
mL Schlenk flask equipped with a magnetic stirring bar. To the
flask was added 147 mgs (7.05.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 24 hours. After cooling
to RT, 20 ml of THF was added to the flask and the reaction was
precipitated into diethyl ether while stirring vigorously. The
precipitate was isolated by filtration and dried in vacuo yielding
14.148 grams of white solid (PVP MacroRAFT agent).
[0099] The second block (TRIS-VC) was added to the PVP MacroRAFT
agent in a second reaction. Ten grams of PVP MacroRAFT agent
(approx. 1.67.times.10.sup.-3 mol) was added to a 100 mL Schlenk
flask along with 20 mL of 1,4-dioxane and a stir bar. 14.127-g
(3.3.times.10.sup.-2 mol) of TRIS-VC and 54.8 mgs of AIBN
(3.33.times.10.sup.-4 mol) were then added to the flask which was
sealed and purged with N.sub.2 for 60 minutes. The reaction was
then heated for 11 hours in a 60.degree. C. oil bath. The reaction
mixture was dissolved in methanol (creating a dispersion). Dialysis
tubes (Spectra/por 6, MWCO 3500) were filled with the solution and
submerged in 1 L of methanol solvent with slow stirring. The
solvent was changed after 4 h, 19.5 h, and 41.5 h. The tubes were
removed at 48 h and the methanol was removed with a rotary
evaporator. The resulting polymer was dried in a vacuum oven.
[0100] Both the PVP MacroRAFT agent and the block copolymer of NVP
and TRIS-VC were characterized by proton NMR (CDC13) and GPC. The
calculated molecular weight of the block copolymer (MW=10,640
PD=1.30) is higher than the PVP MacroRAFT agent (MW=6,760). In
addition, the NMR spectrum of the block copolymer shows peaks
present from the TRIS-VC block at 0.0 ppm and 0.3 ppm and distinct
peaks from the PVP segments between 1.0-2.5 ppm and 3.0-4.0 ppm.
From the integrations it is estimated that the ratio of NVP:TRIS-VC
is approximated at 29:1 by NMR.
Example C
Synthesis of NVP-b-TRIS-VC (Sequential Addition)
[0101] NVP (10 ml; 0.09 mol.), Xanthate (0.094 g,
4.5.times.10.sup.-4 mol.), AIBN (15 mg, 9.0.times.10-5 mol.), and
1,4 dioxane (10 ml) were added to Schlenk flask. The flask was
sealed and purged with N2 for 1 hour. The flask was then heated at
60.degree. C. for 22 hours. In a separate flask, TRIS-VC (3.81 g,
8.99.times.10-3 mol.), AIBN (15 mg, 9.0.times.10-5 mol.) and
1,4-dioxane (4 ml) were combined, and then the flask was sealed and
purged with N2 for 1 hour. This solution was then carefully added
to the PVP reaction under N2. The flask was then heated for another
21 hours. Conversion of TRIS-VC was measured to be 35% by NMR.
After cooling, methanol was added and the solution dialyzed
(Spectra/por 6, MWCO 3500). The tubes were removed at 40 h and the
methanol removed. The polymer was dried in a vacuum oven. The 1 H
NMR spectrum indicates a composition of approximately 4% of
TRIS-VC, a similar value to the block copolymer in example B (ratio
of NVP:TRIS-VC is approximated at 29:1).
[0102] Note* This approach should yield a block copolymer that has
the change from one segment to the other less well-defined as the
first block copolymer discussed above The second block may actually
be a statistical copolymerization of the TRIS-VC and any remaining
NVP that had not been polymerized at the time of the TRIS-VC
addition. The second "block", is therefore compositionally
heterogeneous. 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.
Example D
Synthesis of various DMA-b-Hydrophobic monomer (Sequential
Addition)
TABLE-US-00001 [0103] Hydrophobic DMA DMA CTR CTR Methacrylate
Reaction (mL) (mol) (mgs) (mol) (ml) HM (mol) 2748-152 10 0.097 175
0.00048 1.40 0.0049 2748-153 10 0.097 175 0.00048 2.12 0.0073
2748-154 10 0.097 350 0.00097 2.12 0.0073 2748-155 10 0.097 350
0.00097 2.80 0.0097 2748-156 10 0.097 88 0.00024 1.12 0.0039
2748-157 10 0.097 88 0.00024 1.70 0.0058 *For reactions-152, -154,
and -156 the hydrophobic methacrylate was
3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate (TDFM).
*For reactions-153, -155, and -157 the hydrophobic methacrylate was
lauryl methacrylate (LMA).
[0104] Note: All reactions were carried out in a similar fashion
using the amounts shown in the table above. Reaction 2748-152 is
described below as an example of the procedure used. Weighed 175
mgs (0.48 mmol) of
S-1-Dodecyl-S-(.alpha.,.alpha.'-dimethyl-.alpha.''-acetic acid)
trithiocarbonate and 35 mgs of AIBN into a 250 ml round bottom
flask. Added 10 ml (97 mmol) of N,N-Dimethylacrylamide (DMA) and 30
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, 1.40
ml (4.9 mmol) of 3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl
methacrylate (TDFM) 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 TDFM addition and precipitated into
diethyl ether. The reaction was stopped 16 hours after TDFM
addition (22 hrs total reaction time). The final product was
precipitated out of the reaction mixture into diethyl ether.
Precipitate contained a cloudy layer in the diethyl ether that was
decanted off and a precipitate that settled that was collected and
dried in the vacuum oven.
[0105] For all of the reactions, both the first precipitate and the
block copolymer of DMA and hydrophobic methacrylate (either TDFM or
LMA) were characterized by proton NMR (CDC13) and GPC (DMF as
eluent). The GPC chromatograms all show a shift in the elution
peaks to shorter times (higher MW) after the addition of the
hydrophobic methacrylate blocks. In addition, the NMR spectra of
the block copolymers for samples -152, -154, and -156 above show a
broad peak at around 4.5 ppm corresponding to the methylene group
adjacent to the methacrylate of
3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl methacrylate (TDFM). The
NMR of the block copolymers for samples -153, -155, and -157 show
peaks for the --CH3 group (0.8 ppm) and --CH2- groups (1.3 ppm) of
the alkyl chain of lauryl methacrylate
Example E
Synthesis of a Matrix of GMA-b-DMA Copolymers where the MW of Each
of the Blocks is Varied
TABLE-US-00002 [0106] TABLE 5 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
[0107] *Note: All reactions were carried out in a similiar fashion
using the amounts shown in the table above. Reaction 2748-1114 is
described below as an example of the procedure used. Weighed 350
mgs (0.97 mmol) of S-1Dodecyl-S-(q
.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.
[0108] Both the first precipitate and the block copolymer of DMA
and GMA were characterized by proton NMR (CDC13) 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 show 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-00003 TABLE 6 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 F
Packaging a Lens with a Surfactant
[0109] An aqueous packaging solution containing 1% by weight of the
silicone-containing surfactant NVP-b-TRIS-VC of Example 1 dissolved
in a borate buffered saline at a pH of 7.2 is placed in a
polypropylene blister package. Next, a balafilcon A contact lens is
immersed in the aqueous packaging solution in the polypropylene
blister package. The package is sealed with foil lidstock and then
autoclaved for 30 minutes at 121.degree. C.
[0110] 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.
* * * * *