U.S. patent application number 12/214321 was filed with the patent office on 2008-10-23 for medical devices having antimicrobial coatings thereon.
Invention is credited to Marcia Kay Ash, Fiona Patricia Carney, Manal M. Gabriel, John Martin Lally, Courtney Flem Morgan, Carol Ann Morris, Yongxing Qiu, Lynn Cook Winterton.
Application Number | 20080260804 12/214321 |
Document ID | / |
Family ID | 23297587 |
Filed Date | 2008-10-23 |
United States Patent
Application |
20080260804 |
Kind Code |
A1 |
Morris; Carol Ann ; et
al. |
October 23, 2008 |
Medical devices having antimicrobial coatings thereon
Abstract
The present invention provides a medical device, preferably a
contact lens, which comprises an antimicrobial coating including at
least one layer of polyquat of formula (I) or (II). The
antimicrobial coating on the medical device of the invention has a
high antimicrobial efficacy against microorganisms including
Gram-positive and Gram-negative bacterial, a low toxicity, low
coefficient of friction, and increased hydrophilicity while
maintaining the desired bulk properties such as oxygen permeability
and ion permeability of lens material. Such lenses are useful as
extended-wear contact lenses. In addition, the invention provides a
method for making a medical device, preferably a contact lens,
having an antimicrobial coating thereon.
Inventors: |
Morris; Carol Ann; (Duluth,
GA) ; Gabriel; Manal M.; (Marietta, GA) ; Qiu;
Yongxing; (Duluth, GA) ; Winterton; Lynn Cook;
(Alpharetta, GA) ; Lally; John Martin; (Lilburn,
GA) ; Ash; Marcia Kay; (Snellville, GA) ;
Carney; Fiona Patricia; (Atlanta, GA) ; Morgan;
Courtney Flem; (Alpharetta, GA) |
Correspondence
Address: |
CIBA VISION CORPORATION;PATENT DEPARTMENT
11460 JOHNS CREEK PARKWAY
DULUTH
GA
30097-1556
US
|
Family ID: |
23297587 |
Appl. No.: |
12/214321 |
Filed: |
June 18, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10287091 |
Nov 4, 2002 |
7402318 |
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12214321 |
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60332289 |
Nov 14, 2001 |
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Current U.S.
Class: |
424/429 ;
424/422; 424/78.04; 514/1.1; 73/10 |
Current CPC
Class: |
A61P 31/00 20180101;
A61L 27/34 20130101; G02B 1/043 20130101; A61L 31/10 20130101 |
Class at
Publication: |
424/429 ;
424/422; 424/78.04; 514/12; 73/10 |
International
Class: |
A01N 25/34 20060101
A01N025/34; A01N 33/12 20060101 A01N033/12; A61K 38/40 20060101
A61K038/40; G01N 19/02 20060101 G01N019/02 |
Claims
1-17. (canceled)
18. A method for producing a medical device having an antimicrobial
coating, comprising the steps of: (a) functionalizing the surface
of the medical device; and (b) covalently coupling polyquats of
formula (I) or (II) to the functionalized surface of the medical
device to form the antimicrobial coating on the medical device
##STR00003## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4,
independently of one another, are C.sub.1-C.sub.10 hydrocarbon
radicals, preferably C.sub.1 to C.sub.6 alkyl radicals or C.sub.1
to C.sub.6 alkyl radicals having one or more hydroxyl groups, more
preferably methyl, ethyl, or benzyl radicals, even more preferably
methyl radicals, wherein A and B, independently of one another, are
n-alkylene groups having 3 to 15 carbon atoms or n-alkylene groups
having 3 to 15 carbon atoms and one or more hydroxyl groups,
wherein the index y is a number from about 10 to 500, preferably a
number from 25 to 400, and more preferably a number from 50 to 300,
wherein X is chlorine, bromine, or iodine, wherein the index n is a
number from about 100 to 5000, preferably a number from 500 to
4000, and more preferably a number from 500 to 3000, wherein
R.sub.5 and R.sub.6, independently of one another, are n-alkyl
groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to 10
carbon atoms and one or more hydroxyl groups.
19. A method of claim 18, wherein said medical device is an
ophthalmic device.
20. A method of claim 19, wherein said ophthalmic lens is a contact
lens.
21. A method of claim 20, wherein the contact lens is
functionalized with a diazirine compound.
22. A method for producing a medical device having a core material
and an antimicrobial coating, comprising applying at least one
layer of polyquats of formula (I) or (II) onto the medical device
##STR00004## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4,
independently of one another, are C.sub.1-C.sub.10 hydrocarbon
radicals, preferably C.sub.1 to C.sub.6 alkyl radicals or C.sub.1
to C.sub.6 alkyl radicals having one or more hydroxyl groups, more
preferably methyl, ethyl, or benzyl radicals, even more preferably
methyl radicals, wherein A and B, independently of one another, are
n-alkylene groups having 3 to 15 carbon atoms or n-alkylene groups
having 3 to 15 carbon atoms and one or more hydroxyl groups,
wherein the index y is a number from about 10 to 500, preferably a
number from 25 to 400, and more preferably a number from 50 to 300,
wherein X is chlorine, bromine, or iodine, wherein the index n is a
number from about 100 to 5000, preferably a number from 500 to
4000, and more preferably a number from 500 to 3000, wherein
R.sub.5 and R.sub.6, independently of one another, are n-alkyl
groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to 10
carbon atoms and one or more hydroxyl groups.
23. A method of claim 22, comprising applying at least one layer of
polyquats of formula (I) in which one of A and B is hexamethylene
radical (--CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2--) and
the respective other one is an n-alkylene group having 6 to 12
carbon atoms.
24. A method of claim 22, wherein the layer of polyquats is applied
onto the medical device by immersing said medical device in a first
solution of polyquat of formula (I) or (II) or by spraying a second
solution of polyquat of formula (I) or (II) onto the surface of
said medical device.
25. A method of claim 24, further comprising applying at least one
layer of polyanionic materials.
26. A method of claim 25, wherein the layer of polyanionic
materials is applied onto the medical device by immersing said
medical device in a first solution of polyanionic materials or by
spraying a second solution of polyanionic materials onto the
surface of said medical device.
27. A method of claim 26, further comprising the steps of: (a)
contacting the core material with a solution of the first polyionic
material to form a layer of the first polyionic material; (b)
optionally rinsing said medical device by contacting said medical
device with a rinsing solution; (c) contacting said medical device
with a solution of a second polyionic material to a layer of the
second polyionic material on top of the layer of the first
polyionic material, wherein said second polyionic material has
charges opposite of the charges of the first polyionic material;
and (d) optionally rinsing said medical device by contacting said
lens with the rinsing solution.
28. A method of claim 27, wherein at least one of said contacting
occurs by immersion said medical device in a solution.
29. A method of claim 27, wherein at least one of said contacting
occurs by spraying a solution onto the medical device.
30. A method of claim 27, wherein said method comprises repeating
steps (a) through (D between 3 to 20 times.
31. A method of claim 26, wherein said method comprises dipping
said medical device in a solution containing a polyanionic material
and polycationic material in an amount such that the molar charge
ratio of said solution is from about 3:1 to about 100:1.
32. A method of claim 31, wherein said molar charge ratio of said
solution is 10:1.
33. A method for producing a contact lens having an antimicrobial
coating, comprising the steps of: (a) forming a mold for making the
contact lens, wherein the mold comprises a first mold portion
defining a first optical surface and a second mold portion defining
a second optical surface, wherein said first mold portion and said
second mold portion are configured to receive each other such that
a contact lens-forming cavity is formed between said first optical
surface and said second optical surface; (b) applying a
transferable antimicrobial coating, using a layer-by-layer
polyelectrolyte deposition technique, onto at least one of said
optical surface, wherein the transferable antimicrobial coating
comprises at least one layer of polyquat of formula (I) or (II)
##STR00005## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4,
independently of one another, are C.sub.1-C.sub.10 hydrocarbon
radicals, preferably C.sub.1 to C.sub.6 alkyl radicals or C.sub.1
to C.sub.6 alkyl radicals having one or more hydroxyl groups, more
preferably methyl, ethyl, or benzyl radicals, even more preferably
methyl radicals, wherein A and B, independently of one another, are
n-alkylene groups having 3 to 15 carbon atoms or n-alkylene groups
having 3 to 15 carbon atoms and one or more hydroxyl groups,
wherein the index y is a number from about 10 to 500, preferably a
number from 25 to 400, and more preferably a number from 50 to 300,
wherein X is chlorine, bromine, or iodine, wherein the index n is a
number from about 100 to 5000, preferably a number from 500 to
4000, and more preferably a number from 500 to 3000, wherein
R.sub.5 and R.sub.6, independently of one another, are n-alkyl
groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to 10
carbon atoms and one or more hydroxyl groups; (c) positioning said
first mold portion and said second mold portion such that said mold
portions receive each other and said optical surfaces define said
contact lens forming cavity; (d) dispensing a polymerizable
composition into said contact lens-forming cavity; (e) curing said
polymerizable composition within said contact lens-forming cavity
such that the contact lens is formed, whereby at least a portion of
said transferable coating detaches from said at least one optical
surface of said mold portion and reattaches to said formed contact
lens such that said contact lens becomes coated with the
antimicrobial coating.
34. A method of claim 32, wherein said transferable antimicrobial
coating is applied onto at least one of said optical surfaces by
immersing said mold in a first solution of polyquat of formula (I)
or (II) or by spraying a second solution of polyquat of formula (I)
or (II) onto at least one of said optical surfaces.
35-46. (canceled)
Description
[0001] This application claims the benefit under 35 U.S.C.
.sctn.119(e) of United state provisional application Ser. No.
60/332,289 filed Nov. 14, 2001.
[0002] The present invention generally relates to a medical device
having an antimicrobial coating thereon. In particular, the present
invention relates to an ophthalmic lens having an antimicrobial
coating that has antimicrobial efficacy and low cytotoxicity as
well as other desired properties such as low coefficient of
friction, hydrophilicity, and high oxygen permeability and ion
permeability. In addition, this invention provides a method for
making a medical device having an antimicrobial coating.
BACKGROUND
[0003] Contact lenses are often exposed to one or more
microorganisms during wear, storage and handling. They can provide
surfaces onto which the microorganisms can adhere and then
proliferate to form a colony. Microbial adherence to and
colonization of contact lenses may enable microorganisms to
proliferate and to be retained at the ocular surface for prolonged
periods and thereby may cause infection or other deleterious
effects on the ocular health of the eye in which the lens is used.
Therefore, it is desirous to make various efforts to minimize
and/or eliminate the potential for microorganism adhesion to and
colonization of contact lenses.
[0004] Many attempts have been made to develop antimicrobial
medical devices. Two approaches have been proposed. One approach is
to incorporate antimicrobial compounds into a polymeric composition
for molding a contact lens. For example, Chalkley et al. in Am. J.
Opthalmology 1966, 61:866-869, disclosed that germicidal agents
were incorporated into contact lenses. U.S. Pat. No. 4,472,327
discloses that antimicrobial agents may be added to the monomer
before polymerization and locked into the polymeric structure of
the lens. U.S. Pat. Nos. 5,358,688 and 5,536,861 disclose that
contact lenses having antimicrobial properties may be made from
quaternary ammonium group containing organosilicone polymers.
European patent application EP0604369 discloses that
deposit-resistant contact lenses can be prepared from hydrophilic
copolymers that are based on 2-hydroxyethyl methacrylate and
comonomers containing a quaternary ammonium moiety. Another example
is an ocular lens material, disclosed in European patent
application EP0947856A2, which comprises a quaternary phosphonium
group-containing polymer. A further example is U.S. Pat. No.
5,515,117 which discloses contact lenses and contact lens cases
made from materials which comprise polymeric materials and
effective antimicrobial components. There are some disadvantages
associated with this approach for making antimicrobial contact
lenses. First, polymeric compositions having antimicrobial
properties may not possess all properties desired for contact
lenses, especially extended-wear contact lenses, which hinders
their practice uses. Second, antimicrobial compounds may exhibit
greatly diminished activity since they may not in contact with
microorganisms adhered to the surface of contact lens.
[0005] The other approach for making antimicrobial medical devices
is to form antimicrobial coatings, containing leachable or
covalently attached antimicrobial agents, on medical devices.
Antimicrobial coatings containing leachable antimicrobial agents
may not be able to provide antimicrobial activity over the period
of time when used in the area of the human body. In contrast,
antimicrobial coating containing covalently bound antimicrobial
agents can provide antimicrobial activity over a relatively longer
period of time. However, antimicrobial compounds in such coatings
may exhibit greatly diminished activity when comparing the activity
of the unbound corresponding antimicrobial compounds in solution,
unless assisted by hydrolytic breakdown of either the bound
antimicrobial compounds or the coating itself.
[0006] Currently, a wide variety of antimicrobial agents have been
proposed to be used as coatings for contact lenses (see, for
example, U.S. Pat. No. 5,328,954). Prior known antimicrobial
coatings include antibiotics, lactoferrin, metal chelating agents,
substituted and unsubstituted polyhydric phenols, amino phenols,
alcohols, acid and amine derivatives, and quaternary ammonium
group-containing compounds. However, such antimicrobial coatings
have disadvantages and are unsatisfactory. The overuse of
antibiotics can lead to proliferation of antibiotic-resistant
microorganisms. Other coatings may not have broad spectrum
antimicrobial activity, may produce ocular toxicity or allergic
reactions, or may adversely affect lens properties required for
ensuring corneal health and for providing the patient with good
vision and comfort.
[0007] Therefore, there is a need for antimicrobial coatings that
can provide high bactericidal efficacy and broad spectrum
antimicrobial activity coupled with low cytotoxicity. There is also
a need for new contact lenses having antimicrobial coatings, which
have high bactericidal efficacy, a broad spectrum of antimicrobial
activities, and minimal adverse effects on the wearer's ocular
health and comfort. Such contact lenses may have increased safety
as extended-wear contact lenses which could provide comfort,
convenience, and safety.
[0008] One object of the invention is to provide an antimicrobial
coating which has a high antimicrobial efficacy coupled with low
cytotoxicity.
[0009] Another object of the invention is to provide a medical
device having an antimicrobial coating that has a high
antimicrobial efficacy coupled with low cytotoxicity.
[0010] A further object of the invention is to provide a
cost-effective and efficient process for forming an antimicrobial
coating on a medical device.
SUMMARY OF THE INVENTION
[0011] These and other objects of the invention are met by the
various aspects of the invention described herein.
[0012] The invention, in one aspect, provides a medical device
having an antimicrobial surface coating and the following surface
properties: a low coefficient of friction characterized by having
an averaged value of less than 1.4 and a hydrophilicity
characterized by having an averaged contact angle of less than 80
degree. The antimicrobial coating preferably comprises at least one
layer of polymeric quaternary ammonium group-containing compound
(polyquats) and has a balance of high antimicrobial efficacy and
low cytotoxicity.
[0013] The invention, in another aspect, provides a method for
forming an antimicrobial coating on a medical device. The method
comprises applying at least one layer of polymeric quaternary
ammonium group-containing compound on a medical device.
[0014] These and other aspects of the invention will become
apparent from the following description of the presently preferred
embodiments. The detailed description is merely illustrative of the
invention and does not limit the scope of the invention, which is
defined by the appended claims and equivalents thereof. As would be
obvious to one skilled in the art, many variations and
modifications of the invention may be effected without departing
from the spirit and scope of the novel concepts of the
disclosure.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs.
Generally, the nomenclature used herein and the laboratory
procedures are well known and commonly employed in the art.
Conventional methods are used for these procedures, such as those
provided in the art and various general references. Where a term is
provided in the singular, the inventors also contemplate the plural
of that term. The nomenclature used herein and the laboratory
procedures described below are those well known and commonly
employed in the art. As employed throughout the disclosure, the
following terms, unless otherwise indicated, shall be understood to
have the following meanings.
[0016] An "article" refers to an ophthalmic lens, a mold for making
an ophthalmic lens, or a medical device other than ophthalmic
lens.
[0017] A "medical device", as used herein, refers to a device
having surfaces that contact tissue, blood, or other bodily fluids
of patients in the course of their operation or utility. Exemplary
medical devices include: (1) extracorporeal devices for use in
surgery such as blood oxygenators, blood pumps, blood sensors,
tubing used to carry blood and the like which contact blood which
is then returned to the patient; (2) prostheses implanted in a
human or animal body such as vascular grafts, stents, pacemaker
leads, heart valves, and the like that are implanted in blood
vessels or in the heart; (3) devices for temporary intravascular
use such as catheters, guide wires, and the like which are placed
into blood vessels or the heart for purposes of monitoring or
repair; and (4) ophthalmic lenses. In a preferred embodiment,
medical devices are ophthalmic lenses.
[0018] An "ophthalmic lens", as used herein, refers to any lens
intended for use in intimate contact with the eye of the user. This
includes, without limitation, intraocular lenses, ocular implants,
hard contact lenses, soft contact lenses, and corneal onlays.
[0019] The "outer surface" of a lens, as used herein, refers to the
surface of the lens which faces away from the eye during wear. The
outer surface, which is typically substantially convex, may also be
referred to as the front curve of the lens. The "inner surface" of
a lens, as used herein, refers to the surface of the lens which
faces towards the eye during wear. The inner surface, which is
typically substantially concave, may also be referred to as the
base curve of the lens.
[0020] "Ophthalmically compatible", as used herein, refers to a
material or surface of a material which may be in intimate contact
with the ocular environment for an extended period of time without
significantly damaging the ocular environment and without
significant user discomfort. Thus, an ophthalmically compatible
contact lens will not produce significant corneal swelling, will
adequately move on the eye with blinking to promote adequate tear
exchange, will not have substantial amounts of protein or lipid
adsorption, and will not cause substantial wearer discomfort during
the prescribed period of wear.
[0021] "Ocular environment", as used herein, refers to ocular
fluids (e.g., tear fluid) and ocular tissue (e.g., the cornea)
which may come into intimate contact with a contact lens used for
vision correction, drug delivery, wound healing, eye color
modification, or other ophthalmic applications.
[0022] A "monomer" means a low molecular weight compound that can
be polymerized. Low molecular weight typically means average
molecular weights less than 700 Daltons.
[0023] A "macromer" refers to medium and high molecular weight
compounds or polymers that contain functional groups capable of
further polymerization. Medium and high molecular weight typically
means average molecular weights greater than 700 Daltons.
[0024] "Polymer" means a material formed by polymerizing one or
more monomers.
[0025] "Surface modification", as used herein, refers to treating
an article to alter its surface properties. For example, the
surface modification of a contact lens includes, without
limitation, the grafting of monomers or macromers onto polymers to
make the lens biocompatible, deposit resistant, more hydrophilic,
more hydrophobic, or the deposing of polyionic materials (LbL
coating) to increase the lens hydrophilic properties or to impart
antimicrobial or antifungal properties.
[0026] "LbL coating", as used herein, refers to a coating which is
obtained by layer-by-layer ("LbL") deposition of polyelectrolytes
on an article. The LbL coating of an article is not covalently
attached to the surface of the article. Any suitable LbL
polyelectrolyte deposition techniques can be used in the LbL
coating. For example, a pending U.S. patent application Ser. No.
09/199,609, filed on Nov. 25, 1998, discloses an LbL
polyelectrolyte deposition technique that involves consecutively
dipping a substrate into oppositely charged polyionic materials
until a coating of a desired thickness is formed.
[0027] As used herein, "asymmetrical coatings" on an ophthalmic
lens refers to the different coatings on the first surface and the
opposite second surface of the ophthalmic lens. As used herein,
"different coatings" refers to two coatings that have different
surface properties or functionalities.
[0028] A "capping layer", as used herein, refers to the last layer
of a coating material which is applied onto the surface of a
medical device.
[0029] A "polyquat", as used herein, refers to a polymeric
quaternary ammonium group-containing compound.
[0030] As used herein, a "polyionic material" refers to a polymeric
material that has a plurality of charged groups, such as
polyelectrolytes, p- and n-type doped conducting polymers.
Polyionic materials include both polycationic (having positive
charges) and polyanionic (having negative charges) materials.
[0031] An "antimicrobial coating", as used herein, refers to a
coating that impart to a medical device the ability to decrease or
eliminate or inhibit the growth of microorganisms on the surface of
the medical device.
[0032] An "antimicrobial agent", as used herein, refers to a
chemical that is capable of decreasing or eliminating or inhibiting
the growth of microorganisms such as that term is known in the
art.
[0033] The "oxygen transmissibility" of a lens, as used herein, is
the rate at which oxygen will pass through a specific ophthalmic
lens. Oxygen transmissibility, Dk/t, is conventionally expressed in
units of barrers/mm, where t is the average thickness of the
material [in units of mm] over the area being measured and
"barrer/mm" is defined as:
[(cm.sup.3 oxygen)/(cm.sup.2)(sec)(mm.sup.2
Hg)].times.10.sup.-9
[0034] The "oxygen permeability", Dk, of a lens material does not
depend on lens thickness. Oxygen permeability is the rate at which
oxygen will pass through a material. Oxygen permeability is
conventionally expressed in units of barrers, where "barrer" is
defined as:
[(cm.sup.3 oxygen)(mm)/(cm.sup.2)(sec)(mm.sup.2
Hg)].times.10.sup.-10
These are the units commonly used in the art. Thus, in order to be
consistent with the use in the art, the unit "barrer" will have the
meanings as defined above. For example, a lens having a Dk of 90
barrers ("oxygen permeability barrers") and a thickness of 90
microns (0.090 mm) would have a Dk/t of 100 barrers/mm (oxygen
transmissibility barrers/mm).
[0035] The "ion permeability" through a lens correlates with both
the Ionoflux Diffusion Coefficient and the Ionoton Ion Permeability
Coefficient.
[0036] The Ionoflux Diffusion Coefficient, D, is determined by
applying Fick's law as follows:
D=-n'/(A.times.dc/dx)
where n'=rate of ion transport [mol/min]
[0037] A=area of lens exposed [mm.sup.2]
[0038] D=Ionoflux Diffusion Coefficient[mm.sup.2/min]
[0039] dc=concentration difference [mol/L]
[0040] dx=thickness of lens [mm]
[0041] The Ionoton Ion Permeability Coefficient, P, is then
determined in accordance with the following equation:
In(1-2C(t)/C(0))=-2APt/Vd
where: C(t)=concentration of sodium ions at time t in the receiving
cell
[0042] C(0)=initial concentration of sodium ions in donor cell
[0043] A=membrane area, i.e., lens area exposed to cells
[0044] V=volume of cell compartment (3.0 ml)
[0045] d=average lens thickness in the area exposed
[0046] P=permeability coefficient
[0047] An Ionoflux Diffusion Coefficient, D, of greater than about
0.2.times.10.sup.-3 mm.sup.2/min is preferred, while greater than
about 0.64.times.10.sup.-3 mm.sup.2/min is more preferred and
greater than about 1.0.times.10.sup.-3 mm.sup.2/min is most
preferred.
[0048] An "averaged value of coefficient of friction" refers to a
value of coefficient of friction, which is obtained by averaging
measurements of at least 3 individual medical devices.
[0049] An "averaged contact angle" refers to a contact angle
(Sessile prop), which is obtained by averaging measurements of at
least 3 individual medical devices.
[0050] In general, the present invention is directed to a medical
device having a core material and an antimicrobial surface coating
(hereinafter antimicrobial coating) formed thereon and the
following surface properties: a low coefficient of friction
characterized by having an averaged value of less than 1.4 and a
hydrophilicity characterized by having an averaged contact angle of
less than 80 degree. The antimicrobial coating can comprise any
known suitable antimicrobial agents. Exemplary antimicrobial agents
include, without limitation, antibiotics, lactoferrin, metal
chelating agents, substituted and unsubstituted polyhydric phenols,
amino phenols, alcohols, acid and amine derivatives, and quaternary
ammonium group-containing compounds. Antimicrobial agents in the
antimicrobial coating of a medical device can be covalent bound to
or entrapped to the medical device.
[0051] In particular, the present invention is directed to a
medical device, preferably an ophthalmic lens, more preferably a
contact lens, having an antimicrobial coating comprising at least
one layer, preferably one capping layer, of polymeric quaternary
ammonium salt compounds or the like. Surprisingly, it has been
discovered that a previously known polymeric quaternary ammonium
salt compound (polyquat) of formula (I) or (II)
##STR00001##
can be used to form on a contact lens an antimicrobial coating
having a high antimicrobial efficacy and low cytotoxicity.
Especially, when such antimicrobial coating is formed on a contact
lens which is made from ophthalmically compatible materials, for
example, materials disclosed in U.S. Pat. No. 5,849,811, it
provides high antimicrobial activity coupled with low cytotoxicity,
increases surface hydrophilicity, decreases coefficient of
friction, and has a minimal adverse effects on the desirable bulk
properties of the lens, such as oxygen permeability, ion
permeability, and optical properties. Coefficient of friction may
be one of important parameters that may affect the on-eye movement
and thereby the wearer's comfort. High coefficient of friction may
increase the likelihood of damaging mechanically the ocular
epithelia and/or may lead to ocular discomfort. An antimicrobial
coating of the present invention may find particular use in
extended-wear contact lenses.
[0052] In formula (I), R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are
identical or different from one another. They are C.sub.1-C.sub.10
hydrocarbon radicals, preferably C.sub.1 to C.sub.6 alkyl radicals
or C.sub.1 to C.sub.6 alkyl radicals having one or more hydroxyl
groups, more preferably methyl, ethyl, or benzyl radicals, even
more preferably methyl radicals.
[0053] In formula (I), A and B are identical or different from one
another. They are n-alkylene groups having 3 to 15 carbon atoms or
n-alkylene groups having 3 to 15 carbon atoms and one or more
hydroxyl groups. Preferably, either one of A and B is hexamethylene
radical (--CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2--).
More preferably, either one of A and B is hexamethylene radical
(--CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2--) and the
respective other one is an n-alkylene group having 6 to 10 carbon
atoms. Even more preferably, either one of A and B is hexamethylene
radical (--CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2--) and
the respective other one is an n-alkylene group having 8 to 10
carbon atoms.
[0054] Where either one of A and B is hexamethylene radical
(--CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2--) and the
respective other one is an n-alkylene radical having 6 to 12 carbon
atoms, the polyquat of formula (I) will be represented by PQ6-x, in
which x represents the number of carbon atoms of n-alkylene
radical.
[0055] It is possible as well to provide the polymer chains with
varying proportions of alkylene groups of different lengths. For
example, one of A and B may be hexamethylene radical
(--CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2--), while the
respective other one is n-alkylene radical having 6, 8, 10, or 12
carbon atoms, and these being present in different proportions. It
is possible, for example, to produce polymers which contain 80% of
hexamethylene units and 10% each of decamethylene and
dodecamethylene groups. Depending on the starting material used,
these different alkylene groups may be distributed statistically or
in a more or less orderly fashion throughout the polymer chain.
[0056] In formula (I), the index y characterizes the chain length
of the polymer of formula (I) and is a number from about 10 to 500,
preferably a number from 25 to 400, and more preferably a number
from 50 to 300. X is chlorine, bromine, or iodine.
[0057] In formula (II), X is chlorine, bromine, or iodine. The
index n characterizes the chain length of the polymer of formula
(II) and is a number from about 100 to 5000, preferably a number
from 500 to 4000, and more preferably a number from 500 to 3000.
R.sub.5 and R.sub.6 are identical or different from one another.
They are n-alkyl groups having 1 to 10 carbon atoms or n-alkyl
groups having 1 to 10 carbon atoms and one or more hydroxyl groups.
Preferably, R.sub.5 and R.sub.6 are identical and methyl
groups.
[0058] Methods for making a polymer of formula (I) are well known
in the art. Reference is made in this context to U.S. Pat. Nos.
2,261,002, 2,271,378 and 3,898,188. Generally, a polymer of formula
(I) can be synthesized by reacting a diamine having of formula
(III)
##STR00002##
with a dihalide of formula XBX, in which R.sub.1, R.sub.2, R.sub.3,
R.sub.4, A, B, and X are as defined above.
[0059] It has also been discovered that an unleachable
antimicrobial coating can be formed on a medical device made from a
core material by covalently attaching at least one layer of
polymers of polyquat of formula (I) to the surface of the medical
device or by non-covalently applying at least one layer of polyquat
of formula (I) onto the surface of the medical device using a
layer-by-layer polyelectrolyte deposition technique. The
antimicrobial activity of the polyquat of formula (I) is not
diminished significantly in the antimicrobial coating formed on the
medical device.
[0060] In a preferred embodiment, a medical device of the invention
comprises a core material and an antimicrobial LbL coating
including at least one polyquat-polyanionic bilayer which is
composed of one layer of a polyanionic material and one layer of
polyquat of formula (I) or (II). In a more preferred embodiment,
the medical device of the invention further comprises a plurality
of polyelectrolyte bilayers. A polyelectrolyte bilayer is composed
of a first layer of a first polyionic material and a second layer
of a second polyionic material having charges opposite of the
charges of the first polyionic material.
[0061] A polycationic material used in the present invention can
generally include any material known in the art to have a plurality
of positively charged groups along a polymer chain. For instance,
suitable examples of such polycationic materials can include, but
are not limited to, poly(allylamine hydrochloride) (PAH),
poly(ethyleneimine) (PEI), poly(vinylbenzyltriamethylamine) (PVBT),
polyaniline (PAN or PANI) (p-type doped) [or sulphonated
polyaniline], polypyrrole (PPY) (p-typed doped), and
poly(pyridinium acetylene).
[0062] A polyanionic material used in the present invention can
generally include any material known in the art to have a plurality
of negatively charged groups along a polymer chain. For example,
suitable polyanionic materials can include, but are not limited to,
polymethacrylic acid (PAAA), polyacrylic acid (PAA),
poly(thiophene-3-acetic acid) (PTAA), poly(4-styrenesulfonic acid)
(PSS), sodium poly(styrene sulfonate) (SPS) and poly(sodium styrene
sulfonate) (PSSS).
[0063] The foregoing lists are intended to be exemplary, but
clearly are not exhaustive. A person skilled in the art, given the
disclosure and teaching herein, would be able to select a number of
other useful polyionic materials.
[0064] In order to alter various characteristics of the coating,
such as thickness, the molecular weight of the polyionic materials
including polyquats can be varied. In particular, as the molecular
weight is increased, the coating thickness generally increases.
However, if the increase in molecular weight increase is too
substantial, the difficulty in handling may also increase. As such,
polyionic materials used in a process of the present invention will
typically have a molecular weight Mn of about 2,000 to about
150,000. In some embodiments, the molecular weight is about 5,000
to about 100,000, and in other embodiments, from about 75,000 to
about 100,000.
[0065] In another preferred embodiment, a medical device of the
invention comprises a core material and an antimicrobial LbL
coating including a capping layer of polyquat of formula (I) or
(II). With such capping layer of polyquat of formula (I) or (II),
an antimicrobial coating on a medical device of the invention can
provide a direct contact with the antimicrobial agents, polyquat of
formula (I) or (II) for microorganisms and thereby have a higher
antimicrobial efficacy.
[0066] In another preferred embodiment, a medical device of the
invention comprises a core material and an antimicrobial LbL
coating including a plurality of layers of polyquat of formula (I)
or (II). Such antimicrobial coating may provide higher
concentration of antimicrobial agents and thereby increase
antimicrobial efficacy.
[0067] In accordance with the present invention, the core material
of a medical device may be any of a wide variety of polymeric
materials. Exemplary core materials include, but are not limited
to, hydrogels, silicone-containing hydrogels, polymers and
copolymers of styrene and substituted styrenes, ethylene,
propylene, acrylates and methacrylates, N-vinyl lactams,
acrylamides and methacrylamides, acrylonitrile, acrylic and
methacrylic acids. A preferred group of polymeric materials forming
ophthalmic lenses are those materials which are highly oxygen
permeable, such as fluorine- or siloxane-containing polymers. In
particular, the polymeric materials described in U.S. Pat. No.
5,760,100 are an exemplary group, and the teachings of this patent
are incorporated herein by reference.
[0068] One embodiment of the invention is a method for producing a
medical device having a core material and an antimicrobial coating
including a capping layer of polyquats of formula (I) or (II),
comprising covalently coupling the polyquats of formula (I) or (II)
to the core material.
[0069] Any known suitable method for covalent coupling of polyquats
to the core material can be used. For example, a contact lens made
from a hydrogel, such as lotrafilcon A, lotrafilcon B, or
balafilcon, is dipped into or sprayed with a solution containing a
diaziridine compound, which is subsequently attached covalently to
the surface of the contact lens via a thermal process, so as to
functionalize the contact lens. Such functionalized lenses can be
placed in a container containing a polyquat solution and then
irradiated with blue light for 30 minutes so that polyquats are
covalently attached to the functionalized lens.
[0070] It should be understood that the surface of the medical
device can be chemically modified before covalently coupling
polyquats to the medical device or a different material can be
first grafted onto or bound to the core material and then
covalently coupled with polyquats.
[0071] Another embodiment of the invention is a method for
producing a medical device having a core material and an
antimicrobial LbL coating including a capping layer of polyquats of
formula (I) or (II) comprising applying the antimicrobial LbL
coating onto the core material using a layer-by-layer
polyelectrolyte deposition technique.
[0072] It has been discovered and disclosed in U.S. application
Ser. No. 09/005,317 that complex and time-consuming pretreatment of
a core material (medical device) is not required prior to
non-covalently binding of a polyionic material to the core
material. By simply contacting a core material of a medical device,
for example, a contact lens, with one or more solutions each
containing one or more polyionic materials, an LbL coating can be
formed on a medical device to modify the surface properties of the
core material of the medical device. An LbL coating can be a single
layer or a bilayer or multiple bilayers.
[0073] Application of an LbL coating may be accomplished in a
number of ways as described in pending U.S. patent applications
(application Ser. Nos. 09/005,317, 09/774,942, 09/775,104), herein
incorporated by reference in their entireties. One coating process
embodiment involves solely dip-coating and dip-rinsing steps.
Another coating process embodiment involves solely spray-coating
and spray-rinsing steps. However, a number of alternatives involve
various combinations of spray- and dip-coating and rinsing steps
may be designed by a person having ordinary skill in the art.
[0074] One dip-coating alternative involves the steps of applying a
coating of a first polyionic material to a core material of a
medical device by immersing said medical device in a first solution
of a first polyionic material; rinsing the medical device by
immersing the medical device in a rinsing solution; and,
optionally, drying the medical device. This procedure can be
repeated using a second polyionic material, with the second
polyionic material having charges opposite of the charges of the
first polyionic material, in order to form a polyionic bilayer.
This bilayer formation process may be repeated a plurality of times
in order to produce a thicker LbL coating. A preferred number of
bilayers is about 5 to about 20 bilayers. While more than 20
bilayers are possible, it has been found that delamination may
occur in some LbL coatings having an excessive number of
bilayers.
[0075] The immersion time for each of the coating and rinsing steps
may vary depending on a number of factors. Preferably, immersion of
the core material into the polyionic solution occurs over a period
of about 1 to 30 minutes, more preferably about 2 to 20 minutes,
and most preferably about 1 to 5 minutes. Rinsing may be
accomplished in one step, but a plurality of rinsing steps can be
quite efficient.
[0076] Another embodiment of the coating process is a single
dip-coating process as described in U.S. Application No. 09 775104,
herein incorporated by reference in its entirety. Such single
dip-coating process involves dipping a core material of a medical
device in a solution containing a negatively charged polyionic
material and a positively charged polyionic material in an amount
such that the molar charge ratio of said solution is from about 3:1
to about 100:1. Multiple bilayers can be formed on a medical device
by using this single dip-coating process.
[0077] Another embodiment of the coating process involves a series
of spray coating techniques. The process generally includes the
steps of applying a coating of a first polyionic material to a core
material of a medical device with a first solution of a first
polyionic material; rinsing the medical device by spraying the
medical device with a rinsing solution; and optionally, drying the
medical device. Similar to the dip-coating process, the
spray-coating process may be repeated with a second polyionic
material, with the second polyionic material having charges
opposite of the charges of the first polyionic material.
[0078] The contacting of the medical device with solution, either
polyionic material or rinsing solution, may occur by a variety of
methods. For example, the medical device may be dipped into both
solutions. One preferred alternative is to apply the solutions in a
spray or mist form. Of course, various combinations may be
envisioned, e.g., dipping the medical device in the polyionic
material followed by spraying the rinsing solution.
[0079] The spray coating application may be accomplished via a
number of methods. For example, a conventional spray coating
arrangement may be used, i.e., the liquid material is sprayed by
application of fluid, which may or may not be at elevated pressure,
through a reduced diameter nozzle which is directed towards the
deposition target.
[0080] Preferably, a spraying process is selected from the group
consisting of an air-assisted atomization and dispensing process,
an ultrasonic-assisted atomization and dispensing process, a
piezoelectric assisted atomization and dispensing process, an
electro-mechanical jet printing process, a piezo-electric jet
printing process, a piezo-electric with hydrostatic pressure jet
printing process, and a thermal jet printing process; and a
computer system capable of controlling the positioning of the
dispensing head of the spraying device on the ophthalmic lens and
dispensing the coating liquid. Those spraying coating processes are
described in U.S. Application No. 60/312,199, herein incorporated
by reference in its entirety. By using such spraying coating
processes, an asymmetrical coating can be applied to a medical
device. For example, the back surface of a contact lens can be
coated with a hydrophilic and/or lubricous coating material and the
front surface of the contact lens can be coated with an
antimicrobial material. It is also possible to produce a coating on
a contact lens, the coating having a functional pattern so as to
provide simultaneously multiple benefits to a wearer.
[0081] In accordance with the present invention, polyionic material
solutions can be prepared in a variety of ways. In particular, a
polyionic solution of the present invention can be formed by
dissolving the polyionic material(s) in water or any other solvent
capable of dissolving the materials. When a solvent is used, any
solvent that can allow the components within the solution to remain
stable in water is suitable. For example, an alcohol-based solvent
can be used. Suitable alcohols can include, but are not limited to,
isopropyl alcohol, hexanol, ethanol, etc. It should be understood
that other solvents commonly used in the art can also be suitably
used in the present invention.
[0082] Whether dissolved in water or in a solvent, the
concentration of a polyionic material in a solution of the present
invention can generally vary depending on the particular materials
being utilized, the desired coating thickness, and a number of
other factors. However, it may be typical to formulate a relatively
dilute aqueous solution of polyionic material. For example, a
polyionic material concentration can be between about 0.001% to
about 0.25% by weight, between about 0.005% to about 0.10% by
weight, or between about 0.01% to about 0.05% by weight.
[0083] In general, the polyionic solutions mentioned above can be
prepared by any method well known in the art for preparing
solutions. For example, in one embodiment, a polyanionic solution
can be prepared by dissolving a suitable amount of the polyanionic
material, such as polyacrylic acid having a molecular weight of
about 90,000, in water such that a solution having a certain
concentration is formed. In one embodiment, the resulting solution
is a 0.001 M PAA solution. Once dissolved, the pH of the
polyanionic solution can also be adjusted by adding a basic or
acidic material. In the embodiment above, for example, a suitable
amount of 1 N hydrochloric acid (HCl) can be added to adjust the pH
to 2.5.
[0084] Polycationic solutions can also be formed in a manner as
described above. For example, in one embodiment, poly(allylamine
hydrochloride) having a molecular weight of about 50,000 to about
65,000 can be dissolved in water to form a 0.001 M PAH solution.
Thereafter, the pH can also be adjusted to 2.5 by adding a suitable
amount of hydrochloric acid.
[0085] In some embodiments of the present invention, it may be
desirable to apply a solution containing both polyanionic and
polycationic materials within a single solution. For example, a
polyanionic solution can be formed as described above, and then
mixed with a polycationic solution that is also formed as described
above. In one embodiment, the solutions can then be mixed slowly to
form the coating solution. The amount of each solution applied to
the mix depends on the molar charge ratio desired. For example, if
a 10:1 (polyanion:polycation) solution is desired, 1 part (by
volume) of the PAH solution can be mixed into 10 parts of the PAA
solution. After mixing, the solution can also be filtered if
desired.
[0086] A medical device of the invention can also be made by first
applying an antimicrobial coating to a mold for making a medical
device and then transfer-grafting the antimicrobial coating to the
medical device made from the mold, in substantial accordance with
the teachings of U.S. patent application (Ser. No. 09/774,942),
herein incorporated by reference in its entirety.
[0087] Methods of forming mold sections for cast-molding a contact
lens are generally well known to those of ordinary skill in the
art. The process of the present invention is not limited to any
particular method of forming a mold. In fact, any method of forming
a mold can be used in the present invention. However, for
illustrative purposes, the following discussion has been provided
as one embodiment of forming a mold on which a color image can be
printed in accordance with the present invention.
[0088] In general, a mold comprises at least two mold sections (or
portions) or mold halves, i.e. first and second mold halves. The
first mold half defines a first optical surface and the second mold
half defines a second optical surface. The first and second mold
halves are configured to receive each other such that a contact
lens forming cavity is formed between the first optical surface and
the second optical surface. The first and second mold halves can be
formed through various techniques, such as injection molding. These
half sections can later be joined together such that a contact
lens-forming cavity is formed therebetween. Thereafter, a contact
lens can be formed within the contact lens-forming cavity using
various processing techniques, such as ultraviolet curing.
[0089] Examples of suitable processes for forming the mold halves
are disclosed in U.S. Pat. Nos. 4,444,711 to Schad; 4,460,534 to
Boehm et al.; 5,843,346 to Morrill; and 5,894,002 to Boneberger et
al., which are also incorporated herein by reference.
[0090] Virtually all materials known in the art for making molds
can be used to make molds for making contact lenses. For example,
polymeric materials, such as polyethylene, polypropylene, and PAAMA
can be used. Other materials that allow UV light transmission could
be used, such as quartz glass.
[0091] Once a mold is formed, a transferable antimicrobial LbL
coating, which comprises at least one layer of polyquat of formula
(I) or (II), can be applied onto the optical surface (inner
surface) of one or both mold portions by using the above-described
LbL deposition techniques. The inner surface of a mold portion is
the cavity-forming surface of the mold and in direct contact with
lens-forming material. A transferable antimicrobial LbL coating can
be applied onto the mold portion defining the posterior (concave)
surface of a contact lens or on the mold section defining the
anterior surface of a contact lens or on both mold portions.
[0092] Once a transferable antimicrobial LbL coating is applied
onto the optical surface of one or both mold portions, a lens
material can then be dispensed into the contact lens forming cavity
defined by the assembled mold halves. In general, a lens material
can be made from any polymerizable composition. In particular, when
forming a contact lens, the lens material may be an
oxygen-permeable material, such as flourine- or siloxane-containing
polymer. For example, some examples of suitable substrate materials
include, but are not limited to, the polymeric materials disclosed
in U.S. Pat. No. 5,760,100 to Nicolson et al., which is
incorporated herein by reference. The lens material can then be
cured, i.e. polymerized, within the contact lens-forming cavity to
form the contact lens, whereby at least a portion of the
transferable coating detaches from the optical surface and
reattaches to the formed contact lens.
[0093] Thermal curing or photo curing methods can be used to curing
a polymerizable composition in a mold to form an ophthalmic lens.
Such curing methods are well-known to a person skilled in the
art.
[0094] The previous disclosure will enable one having ordinary
skill in the art to practice the invention. In order to better
enable the reader to understand specific embodiments and the
advantages thereof, reference to the following examples is
suggested.
Example 1
Preparation of Coating Solutions
Polyacrylic Acid (PAA) Solution
[0095] A solution of polyacrylic acid (PAA) having an averaged
molecular weight of about 90,000 is prepared by dissolving a
suitable amount of PAA in water to have [PAA]=0.001 M. PAA
concentration is calculated based on the repeating unit in PAA.
Once dissolved, the pH of the PAA solution is adjusted to a desired
value.
Poly(allylamine hydrochloride) (PAH) Solution
[0096] A solution of poly(allylamine hydrochloride) (PAH) having an
averaged molecular weight of about 60,000 is prepared by dissolving
a suitable amount of the material in water to form a 0.001 M PAH
solution. PAH concentration is calculated based on the repeating
unit in PAH. Once dissolved, the pH of the PAH solution is adjusted
to a desired value.
Polyquat (PQ) Solutions
[0097] A solution of polyquat (PQ6-6) of formula (I), in which
R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are methyl groups, and A and
B are hexamethylene groups, is prepared by dissolving a suitable
amount of PQ6-6 in water to have a desired PQ6-6 concentration.
Once dissolved, the pH of the PQ6-6 solution is adjusted to a
desired value.
[0098] A solution of polyquat (PQ6-10) of formula (I), in which
R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are methyl radicals, and A
and B are hexamethylene and decamethylene groups respectively, is
prepared by dissolving a suitable amount of PQ6-10 in water to have
a desired PQ6-6 concentration. Once dissolved, the pH of the PQ6-10
solution is adjusted to a desired value.
[0099] A solution of polyquat (PQ6-12) of formula (I), in which
R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are methyl groups, and A and
B are hexamethylene and dodecamethylene respectively, is prepared
by dissolving a suitable amount of PQ6-12 in water to have a
desired PQ6-6 concentration. Once dissolved, the pH of the PQ6-12
solution is adjusted to a desired value.
[0100] A solution of poly(diallyldimethylammonium chloride)
(PDADMAC) is prepared by dissolving a suitable amount of PDADMAC in
water to have a desired PDADMAC concentration.
[0101] Once dissolved, the pH of the PDADMAC solution is adjusted
to a desired value.
Example 2
Preparation of Contact Lenses Having LbL Coatings
[0102] This example illustrates LbL coatings and several types of
antimicrobial coatings which are formed on soft contact lenses made
of a fluorosiloxane hydrogel material, lotrafilcon A.
(1) Coating comprising four and half bilayers:
[0103] PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA
[0104] The contact lenses are dipped in a PAA solution (0.001 M,
pH2.5) for 30 min, rinsed with ultra-pure water, then dipped in a
PAH solution (0.001 M, pH7.5) for 5 minutes, rinsed with ultra-pure
water for 1 minute. Three more bilayers are added by alternatively
dipping in the solutions of PAA (0.001 M, pH 3.5) and PAH (0.002M,
pH 7.5), with a rinse step in-between. The contact lenses with four
bilayers of polyelectrolytes is dipped in the PAA solution (0.001
M, pH 3.5) and rinsed with ultra-pure water for 1 minute. The
lenses are then packaged in saline and sterilized.
(2) Antimicrobial Coating comprising 6 Bilayers:
[0105] PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PA/PAH/PAA/PQ6-12
[0106] The contact lenses are dipped in a PAA solution (0.001 M,
pH2.5) for 30 min, rinsed with ultra-pure water, then dipped in a
PAH solution (0.001 M, pH7.5) for 5 minutes, rinsed with ultra-pure
water for 1 minute. Four more bilayers are added by alternatively
dipping in the solutions of PAA (0.001 M, pH 3.5) and PAH (0.002M,
pH 7.5), with a rinse step in-between. The contact lenses with five
bilayers of polyelectrolytes is dipped in the PAA solution (0.001
M, pH 3.5) and rinsed with ultra-pure water for 1 minute. Finally,
a capping layer of PQ6-12 is deposited by dipping lenses in a
PQ6-12 solution (300 ppm, pH 6.5). The lenses are then packaged in
saline and sterilized.
(3) Antimicrobial Coating Comprising 5 Bilayers:
[0107] PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-12
[0108] The contact lenses are dipped in a PAA solution (0.001 M,
pH2.5) for 30 minutes, dipped in a PAH solution (0.001 M, pH4.5)
for 5 minutes, rinsed with ultra-pure water, dipped in the PAA
solution for 5 minutes, and rinsed with ultra-pure water. This
procedure of dipping in an alternative fashion in the PAH and PAA
solutions for 5 minutes and rinsing with water between two dipping
steps is repeated until four and half bilayers with PAA as the
outer layer are formed on the lenses. Then the lenses are dipped in
a PQ6-12 solution (300 ppm, pH5.1) for 5 minutes, followed by a
water rinsing step. The lenses are then packaged in saline and
sterilized.
(4) Antimicrobial Coating Comprising 5 Bilayers:
[0109] PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-10
[0110] The contact lenses are dipped in a PAA solution (0.001 M,
pH2.5) for 30 minutes, then dipped in a PAH solution (0.001 M,
pH4.5) for 5 minutes, rinsed with ultra-pure water, then dipped in
the PAA solution for 5 minutes, rinsed with ultra-pure water. This
procedure of dipping in an alternative fashion in the PAH and PAA
solutions for 5 minutes and rinsing with water between two dipping
steps is repeated until four and half bilayers with PAA as the
outer layer are formed on the lenses. Then the lenses are dipped in
a PQ6-10 solution (300 ppm, pH5.4) for 5 minutes, followed by water
rinsing step. The lenses are then packaged in saline and
sterilized.
(5) Antimicrobial Coating Comprising 5 Bilayers:
[0111] PA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-6
[0112] The contact lenses are dipped in PAA (0.001 M, pH2.5) for 30
min, then dipped in PAH (0.001 M, pH4.5) for 5 min, rinsed with
ultra-pure water, then dipped in PAA solution for 5 min, rinsed
with ultra-pure water. This procedure of dipping in an alternative
fashion in the PAH and PAA solutions for 5 minutes and rinsing with
water between two dipping steps is repeated until four and half
bilayers with PAA as the outer layer are formed on the lenses. Then
the lenses are dipped in a PQ6-6 solution (300 ppm, pH5.9) for 5
min, followed by water rinsing step. The lenses are then packaged
in saline and sterilized.
(6) Antimicrobial Coating comprising 6 bilayers:
[0113]
PA/PAH/PAA/PQ6-10/PAA/PQ6-10/PAA/PQ6-10/PAA/PQ6-10/PA/PQ6-10
[0114] The contact lenses are dipped in a PAA solution (0.001 M,
pH2.5) for 30 minutes, then dipped in a PAH solution (0.001 M,
pH4.5) for 5 min, and then rinsed with ultra-pure water. The lenses
with the first bilayer formed thereon are then dipped in the PAA
solution for 5 minutes, rinsed with ultra-pure water and then
dipped in a PQ6-10 solution (300 ppm, pH5.4) for 5 minutes, rinsed
with water, and then dipped in the PAA solution and rinsed with
water. The procedure comprising 5-minute dips in the PQ6-10
solution and in the PAA solution and water rinse steps between two
dipping steps is repeated until a desired number of bilayers with
either PAA or PQ6-10 as the outer layer are achieved. The lenses
are then packaged in saline and sterilized.
(7) Antimicrobial Coating Comprising 6 Bilayers:
[0115]
PAA/PAH/PAA/PDADMAC/PAA/PDADMAC/PAA/PDADMAC/PAA/PDADMAC/PAA/PDADMAC
[0116] The contact lenses are first dipped in a PAA solution (0.001
M, pH2.5) for 30 minutes, then dipped in a PDADMAC solution (0.001
M, pH 3.5) for 5 minutes, rinsed with ultra-pure water for 1
minute, then dipped in a PAA solution (0.001 M, pH 4.4) for 5
minutes, rinsed with ultra-pure water for 1 minute. This procedure
of dipping in an alternative fashion in the PDADMAC and PAA
solutions for 5 minutes and rinsing with water between two dipping
steps is repeated until a desired number (from 5 to 10) of bilayers
with PDADMAC as the outer layer are formed on the lenses. The
lenses are then packaged in saline and sterilized.
[0117] It has been found that the pH of the polyquat solution used
in the coating process can affect the quality of the antimicrobial
coating, such as polyquat coverage. When the pH of the polyquat
solution used in the coating process is low (e.g., less than 2.5)
or high (e.g., higher than 7.0), delamination of the LbL coating
can occur. Preferably, the pH of the polyquat solution used in the
coating process is from about 3.0 to about 7.0, in order to obtain
an antimicrobial coating with good polyquat coverage. It has also
been found that there is no need for adjusting the pH of the
polyquat solution used in the coating process. The unadjusted pH of
the polyquat solution (300 ppm) generally is from about 5.0 to
about 6.0, which is within the preferred pH range.
Example 3
[0118] This example illustrates how to produce a
covalently-attached antimicrobial coating on a contact lens made of
lotrafilcon A, lotrafilcon B, or Balafilcon.
[0119] The contact lens is functionalized by spraying with or
dipped into a diaziridine compound and then covalently coupling the
diaziridine compound to the contact lens via a thermal process.
Such functionalised lens is placed in an open dish containing a
polyquat (PQ6-6, PQ6-10, PQ6-12, or PDADMAC) solution of about 10
.mu.g/ml and irradiated with blue light for 30 minutes.
Example 4
[0120] Coefficient of friction of a contact lens can be measured by
a sled-on-block type of friction tester as follow. Under a certain
load (e.g., about 3 grams), a contact lens is slid back and forth,
at a prescribed speed, against a biologically relevant substrate
and both the normal force (N) and the tangential force (F.sub.T)
are measured. The coefficient of friction of the contact lens is
calculated based on the equation of .mu.=F.sub.T/N.
[0121] A preferred friction tester comprises: a stationary lens
holder assembly, a biologically relevant substrate, a horizontally
movable platform, and a plurality of force measuring means.
[0122] The stationary lens holder assembly preferably comprises an
"A-shaped" holder bracket and a lens holder having a
lens-supporting surface. The lens supporting surface of the lens
holder has a convex curvature capable of accommodating the back
(concave) surface of a contact lens. The lens holder is preferably
held by a means in the center of the "A-shaped" holder bracket. The
head end of the "A-shaped" stationary sample holder bracket is
connected to a first force measuring means (e.g., a load cell from
Transducer Techniques) by, for example, a Kevlar.RTM. fiber. The
two foot end of the "A-shaped" holder bracket are connected to
nylon string attached with two 1/2'' steel extension springs. The
first force measuring means and the steel extension springs are
mounted to the frame of the tester.
[0123] The horizontally movable platform can be, for example, a
table platform x-table) which moves uniaxially at various speeds
and accelerations. The x-table preferably has a dimension of 163 mm
long and 19.1 mm wide and can provide a test area having about 140
mm long and about 14.7 mm wide. An example of the x-table is a
Model 41 Linear Positioner which is powered by a ZETA Drive
Compumotor (Parker Hannifin Corporation), which operates
unidirectional at maximum velocities of 1800 mm/min and
accelerations of 9000 mm/s.sup.2.
[0124] The biologically relevant substrate can be any material and
preferably is a powder-free surgical glove with Biogel.RTM.
Coating" from Regent.RTM.. Preferably, the finger of the glove is
cut into a single rectangular strip, and stretched and attached to
the x-table by a physical means, for example, jumbo paper clips.
Before testing, the substrate attached onto the x-table is
lubricated with two drops of a desired lubricant, for example,
ultra pure water or Softwear.RTM. saline (CIBA vision). Any air
between the substrate and the x-table should be removed. The
desired lubricant should be applied evenly on the substrate. The
substrate should be even and consistent throughout.
[0125] Preferably, there are three force-measuring means, a first,
a second and a third force-measuring means. Any suitable known
force-measuring means can be used. An example is a 100-gram load
cells from Transducer Techniques. The first force-measuring means
is attached to the sample holder to measure tangential forces
(friction forces, F.sub.T) in two opposite directions. The second
and third force-measuring means reside under the x-table to measure
normal forces (N) in the downward direction. The other load cell
Values outputted by the normal load cells are converted to grams by
a Versatile Amplifier/Conditioner (Transducer Techniques).
[0126] Measurements of coefficient of friction is performed on the
preferred friction tester as follows. A contact lens is placed on a
lens holder with the back surface of the contact lens against the
lens-supporting surface of the lens hold. The lens holder with the
contact lens is assembled with the "A-shaped" holder bracket and
then placed in contact with a desired lubricated substrate. This
substrate is mounted to a horizontally movable table platform that
is capable of moving uniaxially at various speeds and
accelerations. About 3 grams of weight is loaded onto the lens
holder. This load may represent the force pressed on a contact lens
by a blink of eyelids. The tree force-measuring means (3 Load cells
from Transducer Techniques) measure simultaneously the normal (N)
and frictional (F.sub.T) forces that are produced from the
interaction between the contact lens and the substrate lubricated
with a desired lubricant. Multiple data points are taken during a
measurement of coefficient of friction of a contact lens. At each
data point, the coefficient of Friction .mu., is calculated as
follows:
.mu.=F.sub.T/N
in which F.sub.T represent actual data reading at each point
obtained by the first force measuring means after correcting for
the preloading provided by the springs (tangential load cell)
during sliding of the substrate against the contact lens and
preferably has a unit of gram; N is the sum of N.sub.1 and N2; N1
represents actual data reading at each point obtained by the second
force-measuring means after correcting for any preloading by the
test assembly (normal load cell#1) during sliding of substrate
against the contact lens and preferably has a unit of gram; and
N.sub.2 represents actual data reading at each point obtained by
the third force-measuring means after correcting for any preloading
by the test assembly (normal load cell#2) during sliding of
substrate against the contact lens and has preferably a unit of
gram. The average (.mu..sub.Ave) of all .mu. 's at every data point
will be used to represent the value of coefficient of friction of a
contact lens.
[0127] More preferably, the friction tester further comprises a
computer system that controls the tester, collects readings of the
normal and tangential forces simultaneously as the
biologically-relevant substrate interacts with contact lens,
calculates coefficient of friction, and records and charts the
forces (F.sub.T and N) and the coefficient of friction (.mu.) at
each data point during testing.
Example 5
Antimicrobial Activity of Contact Lenses Having one or more Layer
of Polyquats
[0128] Contact lenses having an LbL coating of
PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA (41/2 bilayers) and a capped
layer of polyquat are tested for antimicrobial activity against
Pseudomonas aeruginosa # 3, which is isolated from a corneal
ulcer.
[0129] Effects of pH of polyquat coating solutions on antimicrobial
activity are studied. The contact lenses are prepared as described
in Example 2. The pHs of the PQ6-12 solution used in forming the
capping layer of polyquat are from 2.5 to 6.5. The contact lenses
are incubated for three days with Pseudomonas aeruginosa GSU # 3
suspended in PBS. The inoculum size is 1.0.times.10.sup.4 cfu/ml.
No significant difference in antimicrobial activity of contact
lenses is observed for those solution having a pH of from 3.0 to
6.5. For further antimicrobial activity assays, the pH of the
polyquat solution is within 3.0 to 6.5.
[0130] The contact lenses are prepared as described in Example 2.
The pHs of the PQ6-12 solution used in forming the capping layer of
polyquat are 5.5 and 6.5 respectively. The contact lenses are
soaked in a cell suspension of 1.times.10.sup.3 of Pseudomonas
aeruginosa GSU # 3 at 37.degree. C. for 20 hours. Lenses are
removed from the cell suspension and immediately soaked/rinsed in
250 ml of PBS (Dulbecco). The rinsing step is repeated for 3
consecutive times. After rinsing with PBS, each lens is placed on a
petri dish. Molten agar is poured into the petri dish containing
one lens. The agar dish containing the lens is inverted and
incubated at about 30.degree. C. to 35.degree. C. for about 24 to
48 hours.
[0131] As a positive control, contact lenses with coatings, each
having four and half bilayers PAA/PAH/PAA/PAH/PAA/PAH/PAA, are
tested for antimicrobial activity against Pseudomonas aeruginosa
GSU # 3 according to the above-described procedures.
[0132] As a negative control, contact lenses with coatings, each
having four and half bilayers PAA/PAH/PAA/PAH/PAA/PAH/PAA, are
soaked in bleach for 30 minutes and then rinsed with PBS. The
lenses are then inoculated with Pseudomonas aeruginosa GSU # 3 and
antimicrobial activity is tested according to the above-described
procedures.
[0133] Results of antimicrobial activity assays are shown in Table
1.
TABLE-US-00001 TABLE 1 Colonies on the lenses No. 1 lens No. 2 lens
No. 3 lens Lens coated W/PQ6-12 .sup.1 3 1 0 Lens coated W/PQ6-12
.sup.2 0 2 2 Positive control ++++* ++++* ++++* Negative control
none none none *Colonies are observed all over the lens. Confluent
growth is also observed on the plate. .sup.1 pH of the PQ6-12
coating solution is 5.5. .sup.2 pH of the PQ6-12 coating solution
is 6.5.
[0134] Surface antimicrobial activities of contact lenses with
antimicrobial coating are also assayed. Contact lenses are prepared
as described in Example 2 and each contains an antimicrobial
coating of PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PA (41/2 bilayers) and a
capped layer of polyquat (PQ6-6, PQ6-10, or PQ6-12). The pHs of the
polyquat solutions (300 ppm) used in forming the capping layer of
polyquat are unadjusted and from about 5.0 to about 6.0. Two types
of control contact lenses are used. Each of the first type of
control contact lenses comprises an LbL coating having 41/2
bilayers, PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA. The second type of
control contact lenses is plasma-coated contact lenses. The
plasma-coated contact lenses are prepared in substantial accordance
with teachings in PCT Publication No. WO 96/31792 to Nicolson et
al. All contact lenses are made of lotrafilcon A. 200 microliter of
inoculum solution (104/CFU of Pseudomonas aeruginosa GSU #3) is
placed on the test lenses, incubated for .about.18 hours at
25.degree. C. A portion of the inoculum is extracted, serially
diluted and plated out on agar plates for comparison to determine
the microbial load of each lens type. At 24 hours, colony counts
are taken from each lens. Results are shown in Table 2.
TABLE-US-00002 TABLE 2 cfu recovered from the Contact lenses
surface of the lens* Control 1 (41/2 bilayers) TNTC.sup.# (solid
lawn of bacteria) Control 2 (plasma-coating) TNTC.sup.# (solid lawn
of bacteria) A capping LbL layer of PQ6-6 377 A capping LbL layer
of PQ6-10 0 A capping LbL layer of PQ6-12 0 *Values averaged over
three tested contact lenses. .sup.#TNTC represents "too numerous to
count".
[0135] Results in Table 2 indicate the antimicrobial activity on
the surface of the contact lenses having antimicrobial coatings.
The antimicrobial coatings with a capping layer of PQ6-12 or PQ6-10
show relatively high antimicrobial efficacy. The antimicrobial
coating with a capping layer of PQ6-6 shows antimicrobial activity
but less than the activity demonstrated by the other antimicrobial
coatings containing PQ6-12 or PQ6-10.
[0136] Contact lenses having a coating comprising covalently
attached PQ6-12 are tested for antimicrobial activity against
Staphylococcus aureus (ATCC 6538). The contact lenses are prepared
as described in Example 3. Lenses to which polyquats are covalently
attached are placed in 0.5 ml of 1.times.10.sup.4 cfu
Staphylococcus aureus (ATCC 6538) in an artificial tear fluid at
37.degree. C. with shaking for 24 hours. The composition and
preparation of the artificial tear fluid is described by Mirejovsky
et al. in Optom. Vis. Sci. 68: 858-864 (1991), herein incorporated
by reference. After 24 hours, the contact lenses are removed and
rinsed 3 times in 250 ml of phosphate buffered saline (PBS) and
then placed in a vial containing 10 ml of Dulbecco's PBS, sonicated
for 6 minutes followed by vortexing for 1-2 minutes. The effluent
from each lens is serially diluted, plated out and incubated
inverted at 35.degree. C. Colonies are counted after about 24 to 48
hours of incubation. As a control, contact lenses made of the same
material (lotrafilcon A) are functionalized with a diaziridine
compound. These control contact lenses are also tested using the
identical antimicrobial activity assay procedure. Number of cfu
recovered from the control contact lenses is about
1.9.times.10.sup.4. Number of cfu recovered from the contact lenses
having a coating comprising covalently attached PQ6-12 is
undetectable.
Example 6
Surface Properties of Contact Lenses Having Antimicrobial
Coatings
[0137] The contact angle generally measures the surface
hydrophilicity of a contact lens. In particular, a low contact
angle corresponds to more hydrophilic surface. Average contact
angles (Sessile prop) of contact lenses are measured using a VCA
2500 XE contact angle measurement device from AST, Inc., located in
Boston, Mass. The averaged contact angle of a contact lens, which
is made of lotrafilcon A and without any coating (LbL or plasma),
is about 112 degree. When such contact lens has a surface
modification through LbL coating or plasma coating, the averaged
contact angle is decreased generally to less than 70 degrees. Where
a contact lens having an antimicrobial coating comprising one or
more layer of polyquat, the averaged contact angle is determined to
be from about 30 degree to about 65 degrees.
[0138] Coefficient of friction (COF) may be one of parameters that
measure the easiness of the on-eye movement of a contact lens. High
coefficient of friction may increase the likelihood of damaging
mechanically the ocular epithelia. The COF is measured as described
in Example 4. Multiple lenses are measured to obtain the averaged
COF. A contact lens without any surface modification (i.e., plasma
treatment or LbL coating), which is made of lotrafilcon A, has an
averaged coefficient of friction of about 1.8. A contact lens
having an LbL or antimicrobial coating has a smaller averaged COF
(Table 3).
TABLE-US-00003 TABLE 3 LbL or Antimicrobial Coating on a Contact
lens (lotrafilcon A) COF PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA 1.32
.+-. 0.12 .sup.1 PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-6 1.29
.+-. 0.11 .sup.1 PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-6/ 1.11
.+-. 0.13 .sup.1 PAA PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-10
1.41 .+-. 0.02 .sup.2 PAA/Q6-6/PAA/Q6-6/PAA/Q6-6/PAA/Q6-6/PAA 1.31
.+-. 0.03 .sup.2 .sup.1 Averaged value based on measurements of 10
lenses. .sup.2 Averaged value based on measurements of 3
lenses.
[0139] It has been found that the desirable bulk properties of the
lens, such as oxygen permeability, ion permeability, and optical
properties are not significantly affected by the antimicrobial
coating comprising one or more layer of polyquat (PQ6-6, PQ6-10 or
PQ6-12) on the lens. The ion permeability of a contact lens
measures the ability of ions to diffuse through the contact lens.
The Dk value of a contact lens is generally a measure of the
ability of a gas, such as oxygen, to diffuse through a contact
lens. A more detailed description of the ion permeability and Dk
value can be obtained by reference to U.S. Pat. No. 5,760,100.
Example 7
[0140] The potency of polyquat against Pseudomonas aeruginosa GSU
#3 is tested at a concentration of 0.5, 1, 5 and 10 ppm. The
inoculum is between 5.times.10.sup.5-1.times.10.sup.6 cfu/ml. There
is more than 3-log reduction demonstrated by the biocidal assay.
Minimum inhibition concentrations (MICs) are determined and shown
in Table 4.
[0141] Cytotoxicity of polyquat is also evaluated according to the
USP Elution Test ("Biological Reactivity Tests, In-Vitro: Elution
Test", The United States Pharmacopeial Convention, Inc.). Cell
cultures, L929 mammalian fibroblasts (ATCC cell line CCL1, NCTC
clone 929), are grown to a near confluent monolayer in 6 well
plates (individual wells are 35 mm diameter). A polyquat solution
is diluted with serum-supplemented cell culture medium at 25% test
solution concentration. The serum-supplemented cell culture medium
is prepared by mixing 1000 mL Eagle's sterile minimum essential
medium (MEM), 100 mL serum, 10 ml L-glutamine solution and
antibiotic-antimycotic solution. Each culture is examined
microscopically after 48 hours using trypan blue for the presence
of morphological changes, reduction in cell density or cell lysis
induced by the polyquat solution. The results of cytotoxicity assay
are shown in Table 4.
TABLE-US-00004 TABLE 4 Polyquat Potency (MIC) Cytotoxicity PQ6-6
2-10 ppm Passed at 50 ppm PQ6-10 0.5 ppm Passed at 25 ppm PQ6-12
0.5 ppm Failed at 25 ppm
[0142] Contact lenses (made of lotrafilcon A, having an LbL coating
of PA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA and contact lenses
(lotrafilcon A) having an antimicrobial coating of
PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA/PQ6-10 are evaluated for
cytotoxicity according to the L929 Cell Growth Assay (Coulter
Counter Method). For this assay, cells grown under controlled
conditions are monitored for their ability to survive and grow
following initial exposure and incubation with extracts of lenses.
The lenses are rinsed with 10 mL of 0.9% Sodium Chloride Injection,
USP, and then extracted using 20 lenses in 10 mL of 0.9% Sodium
Chloride Injection, USP, at 121.+-.2.degree. C. for 1 hour. The
extract is diluted with growth media (serum-supplemented MEM) to
50% extract concentration and is applied to the L929 cells. Cell
counts are determined upon initiation of the test (Initial, Time=0)
and after 72 hours with and without addition of test sample (lens
extract). The calculation of the percent inhibition of cell growth
induced by the extract is determined by comparison of cell growth
for the control cultures to the test cultures. This test evaluated
the ability of cells to survive a toxic insult as measured by
retention of proliferative ability. Results are shown in Table
5.
TABLE-US-00005 TABLE 5 Tests and Control Sample description %
inhibition Test Samples: Contact lenses (lotrafilcon A) with LbL
coatings 12 Contact lenses (lotrafilcon A) with antimicrobial
coatings 10 Control Samples: Sodium Chloride Injection (0.9% NaCl)
(negative control) 0 5% ethanol solution (w/PBS) (positive control)
100
[0143] The results in Table 5 indicate that there is no significant
difference between contact lenses having LbL coatings and contact
lenses having antimicrobial coatings. Both types of contact lenses
can be considered non-cytotoxic since the growth inhibition is less
than 30%, which is the threshold for a cytotoxic response in the
eye.
Example 8
In Vivo Toxicity Tests
[0144] In vivo toxicity of antimicrobial coatings on contact lenses
is tested by trying these contact lenses with antimicrobial
coatings on the eyes of New Zealand white rabbits. Contact lenses,
designed to accommodate rabbit eyes and made of lotrafilcon A, were
manufactured. An antimicrobial coating comprising 4% bilayer
(PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA) and a capping layer of PQ6-12
is applied onto each lens in accordance with the procedure
described in Example 2. The eyes of New Zealand white rabbits are
examined after they wear the contact lenses with the antimicrobial
coatings on eye for 7 days and 6 nights. Microscopic evaluation of
the ocular tissue sections reveals no evidence of corneal or
conjunctival damage in any of the test or control eyes.
Intra-Stromal Corneal Implantation Test
[0145] Control lenses (made of lotrafilcon A and with an LbL
coating comprising 41/2 bilayer,
PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA), and segments of contact
lenses with antimicrobial coatings each comprising a capping layer
of PQ6-12 and 4% bilayer (PAA/PAH/PAA/PAH/PAA/PAH/PAA/PAH/PAA) are
surgically implanted into corneal stroma of New Zealand white
rabbits to evaluate toxicity reactions. The lenses are inserted
into the eye to mid-depth in the corneal stroma. All eyes are
harvested for histopathology after one week of wear. There are no
signs of inflammation.
Intramuscular Implantation Test
[0146] New Zealand white rabbits are implanted with strips of the
antimicrobial contact lenses and the control lenses on the dorsal
side for a period of seven days. The animals are observed daily to
insure proper healing of the implant sites and for clinical sites
of toxicity. The implanted sites are excised from the rabbits and
examined with macroscopic observations and histopathology analysis.
None of the test animals exhibits signs of toxicity over the course
of the study. Microscopic evaluation of the test article sites
indicates no signs of inflammation, fibrosis, hemorrhage, necrosis
of degeneration as compared to the negative or to the predicate
control article sites.
[0147] All results shown in the above examples demonstrate that the
antimicrobial coatings on contact lenses have a high antimicrobial
efficacy, a low toxicity, low coefficient of friction (with an
averaged value of less than 1.4), and increased hydrophilicity
(characterized by an averaged contact angle of less than 80 degree)
while maintaining the desired bulk properties such as oxygen
permeability and ion permeability of lens material. Such lenses are
useful as extended-wear contact lenses.
[0148] Although various embodiments of the invention have been
described using specific terms, devices, and methods, such
description is for illustrative purposes only. The words used are
words of description rather than of limitation. It is to be
understood that changes and variations may be made by those skilled
in the art without departing from the spirit or scope of the
present invention, which is set forth in the following claims. In
addition, it should be understood that aspects of the various
embodiments may be interchanged either in whole or in part.
Therefore, the spirit and scope of the appended claims should not
be limited to the description of the preferred versions contained
therein.
* * * * *