Note: Descriptions are shown in the official language in which they were submitted.
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BACKGROUND OF THE INVENTION
Just as there are marked differences in the
structure and composition of hard contact lenses, cellu-
lose acetate butyrate (CAB) and silicone copolymer gas-
permeable contact lenses and soft contact lenses, thereare also marked differences in the maintenance and care or
treatment with the various types of hard, CAB, silicone
and soft lenses. While patient care and treatment of hard
contact or conventional contact lenses is relatively
s.imple and uncomplicated, the proper care and treatment of
CAB and silicone copolymer lenses tgas-permeable) and the
newer soft and hydrophilic lenses has proved to be more
complex, time consuming and costly to the patient.
The primary difference between the conventional
hard contact lens and the silicone copolymer lenses and
the more complex soft lenses is the hydrophobic nature of
the silicone copolymer lenses and the marked increase in
the polar or water attracting centers of the hydrophilic
gel material from which the soft contact lenses are made.
It is this property of the hydrophilic gel lens that gives
the soft lens its own unique physical properties and
clinical behavior. This polar or water attracting center
of the gel material is represented in the hydroxyethyl
methacrylate bond as a hydroxyl group (-OH) which attracts
and holds large amounts of water. It is this high water
content held in the expanded matrix of the hydrophilic gel
lens which leads to the special difficulties in cleaning
and disinfecting or asepticising the soft hydrophilic
lens. The hydrophilic nature of soft contact lenses makes
the lenses vulnerable to bacterial contamination. While
studies have demonstrated that bacteria cannot penetrate
the actual intromolecular pores of the hydrophilic lens,
except in defective lenses, the bacteria have an affinity
for protein and tear deposits on the surfaces of the lens
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matrix. In particular, the tears and fluids absorbed by
the soft lenses serve as excellent bacterial culture
media. If defects or nicks occur in the lenses either
during manufacture or subsequent patient wear, bacteria
may find a haven to grow and be sheltered from superficlal
lens cleaning and disinfection.
Potentially harmful fungi are also a possible
danger to the soft contact lens. Fungi, like bacteria,
can thrive in tear secretions, other fluids or deposits
and penetrate the lens material directly if enzymatic
degradation of the lens material has taken place.
Similarly, any substantial residual protein-
aceous or tear secretion deposits or lipid deposits re-
maining in or on the lens may readily overwhelm and in-
activate the most effective germicidal components of adisinfecting system, and may thus serve to act as a growth
media for a variety of potentially harmful microorganisms
and fungi. Therefore, it is important that prior to
storing the soft contact lenses in a disinfecting solu-
tion, protein and lipid deposits be removed from -the lens
surfaces so that the disinfectant properties of the steriliz-
ing solution or method will not be overwhelmed by gross
organic or inorganic deposits and pollutants. Therefore,
an effective cleaning step or steps is an essential and
mandatory part of any effective soft lens treatment and
maintenance regimen.
Wetting solutions are used to prepare the con~
tact lenses prior to insertion into the eye and are known
in the prior art. Prior art contact lens wetting solutions
have primarily involved the use of polyvinyl alcohol
as a wetting agent and methyl cellulose or hydroxyethyl
cellulose as viscosity building agent. These prior art
solutions have also contained sufficient amounts of water-
soluble salts, generally sodium chloride, to make them
isotonic or hypertonic with human serum and tear fluid.
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For example, hypertonic wetting solutions are disclosed in
U.S. Patent No. 3,549,747.
Re-wetting solutions are instilled directly into
the eyes when contact lenses are being worn. Such solu-
tions can also be used before or after wearing periods.
The purpose of re-wetting solutions include providing
comfort and relubrication for the eye.
Because of the potential for bacterial contami-
nation, wetting and re-wetting solutions generally include
a preservative system to prevent or inhibit microbial
growth, especially where multi-dose containers of the
solution are prepared. Generally, where no preservative
is employed, single dose containers are utilized, which
result in greater expense.
Preservative systems known in the prior art for
wetting solutions are disclosed in U.S. Patent No. 3,549,747.
Known preservatives include benzalkonium chloride, thimerosal,
chlorhexidine, sorbic acid and potassium sorbate. However,
these compounds have drawbacks in that they can be concen-
trated in the lens matrix and cause irritation, excessive
burning, red eye and lens discoloration, which can prevent
the patient from wearing the lenses or can otherwise be
hypersensitive and annoying to the eye.
With the advent of extended wear contact lenses,
it becomes even more important to avoid such problems,
since those lenses can remain in the eye for several
weeks. Thus, a need has arisen for an effective preserva-
tive system which avoids the use of preservatives known to
cause eye irritation and lens discoloration and which is
suitable for soft contact lenses in a wetting and re-wetting
solution. A need also exists for a soft contact lens
wetting and re-wetting solution which incorporates such a
preservative system. Finally, a need exists for an 'lin-eye'
re-wetting solution that can be--instilled directly into
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the eyes to provide re-lubrication and comfort for the
eyes having such a preservative system.
1~5~776
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SUMMARY OF THE INVENTION
This invention relates to novel and effective
silicone copolymer (gas-permeable) contact lens and soft
contact lens preservative systems and wetting and re-wetting
solutions. More particularly, this invention relates to
highly effective silicone copolymer and soft contact lens
wetting and re-wetting solutions that can be applied
directly into the eye that includes a preservative system
which avoids hypersensitivity and lens discoloration
problems associated with preservatlve systems containing
thimerosal, sorbic acid, potassium chloride or chlor-
hexidine, for example. The invention is especially suit-
able for use with silicone, silicone copolymers and soft
lenses (such as HEMA contact lenses, for example) includ-
ing extended wear contact lenses, and reference to hardlenses includes silcone, silicone copolymers and extended
wear lenses. The invention is also suitable for use in
connection with hard contact lenses. In fact, the wetting
and re-wetting solution can be used directly in the eye by
persons who do not wear contact lenses, such as for relief
of dry eye syndromes, idiopathic ocular discomfort and
other conditions. As used hereinafter and in the claims,
the term "wetting solution" or "wetting composition"
includes re~wetting solutions or compositions that are
suitable for application directly into the eye.
In another aspect, this invention relates to a
soft contact lens wetting and re-wetting composition that
effectively wets the surface of contact lenses, especially
soft and extended wear lenses. The solution is also useful
as an in-eye comfort solution during and after contact lens
wearing periods. The solution can also be used as an in-eye
comfort solution whether or not contact lenses are worn.
In accordance with the invention, a preservative
system is provided that is incorporated in a contact lens
~25677~
wetting and/or re-wetting solution. The preservative
system is effective for maintaining the solution sterile,
preventing bacteria and other organisms from contaminating
the solution after its container has been opened and an
S initial use has been made of a portion of the solution,
for example. While intended primarily for use in connec-
tion with soft contact lenses, including extended wear
lenses, the preservative system may also be used with hard
contact lenses.
The preservative system of the invention is safe
and effective, is not deleterious to the human eye or
ocular tissue, and when present in a wetting solution, can
be instilled directly into the eye. Further, the preser-
vative system does not discolor soft contact lenses and is
not otherwise deleterious to soft lenses. Accordingly,
the shortcomings of preservative systems containing com-
pounds such as thimerosal, sorbic acid, potassium chloride
or chlorhexidine, for example, are avoided.
The preservative system of the invention for use
in a contact lens wetting composition which can be in-
stilled into the eye includes an effective amount of
trimethoprim and at least one adjuvant bactericide com-
prising benzyl alcohol for maintaining the sterility of
the composition. The composition optionally includes
ethylenediamine tetraacetic acid (EDTA) or a water soluble
salt thereof. Generally, the amount of trimethoprim is
from about 0.05% to about 2.0%, the amount of benzyl
alcohol is from about 0.1% to about 5.0% and the amount of
EDTA is from about 0.025% to about 0.5%, all by weight of
the total composition. In addition to acting as an adju-
vant bactericide, the benzyl alcohol functions as an aid
in dissolving the trimethoprim which is present in the
composition.
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In accordance with another aspect of the present
invention, a method is provided for maintaining the sterility
of contact lens wetting compositions which method includes
providing in the compositions a preserva-tive system in
accordance with the invention. The sterility of the
composition is preserved while avoiding the use of bacte-
ricides which are absorbed by soft lenses and which are
incompatible with ocular tissue or otherwise cause eye
irritation and/or lens discoloration.
In accordance with the preferred aspects of the
present invention, a composition suitable for wetting and
re-wetting contact lenses is provided.
The wetting composition includes a preservative
system and a wetting system. Preferably, the aqueous
wetting composition according to the invention that includes
a wetting system and a preservative system has a tonicity
of from about l.00 to about 1.~5 and a pH of from about
7.0 to about 8.0 and a viscosity of from about 26 to
40 cps.
In accordance with one embodiment of the inven-
tion, an aqueous wetting composition is provided that is
especially suitable for wetting soft contact lenses. The
wetting composition contains a preservative system of the
above description and a wetting component or components.
Any suitable wetting component may be utilized that is
suitable for wetting contact lenses. If the wetting
composition is intended for wetting soft contact lenses,
then the wetting component should be suitable for use with
soft contact lenses.
Generally, the wetting system should be com-
pletely miscible with water at the utili~ed concentrations
and generally should also provide a clear solution. In
addition, the wetting system must not act adversely with
the type of contact lens with which use is intended, nor
~2s677~j
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with other materials present in the solution and, finally,
must not irritate the eye.
The wetting system includes at least one com-
ponent suitable wetting contact lenses. Usually, the
wetting system will include a viscosity-building agent and
- a wetting agent suitable for soft contact lenses. Suit-
able viscosity-buildlng agents include water soluble
cellulosic polymers, which may be synthetic or natural,
for example. Such materials also assist in wetting the
lenses. Suitable wetting agents include polyvinyl alcohol
and polyvinylpyrrolidone and mixtures thereof, for example.
Other suitable viscosity-building agents and wetting
agents for contact lens wetting solutions will be known to
those skilled in the art.
Suitable cellulosic polymers include hydroxy-
ethylcellulose, methylcellulose, carboxymethylcellulose,
natural gums and mixtures thereof. Usually, the amount of
cellulosic polymer present in the composition is from
about 0.05% to about 0.80% by weight of the total compo-
sition.
Usually, the wetting composition will have a
viscosity of about 25 to 40 cps at 25 C. Medium grade
cellulosic polymers are useful for achieving the desired
viscosity.
Preferably, the polyvinyl alcohol utilized is
fully hydrolized. Generally, the amount of polyvinyl
alcohol present in the composition is from about 0.5% to
about 2.5% by weight of the total composition.
Preferably, an additional wetting compound, a
polyvinylpyrrolidone polymer, will be utilized, usually in
an amount of from about 0.5% to about 2.0% by weight of
the total composition.
It is to be understood that the invention is not
limited to the foregoing types of wetting agents and
viscosity-building agents. Any type of material which can
-10- ~25~7~6
be used to provide the desired wetting action and which is
compatible with the preservative system of the present
invention and is otherwise suitable for use in a wetting
solution or a contact lens wetting solution can be utilized.
Compositions in accordance with the invention
have a pH of preferably from about 7.0 to about 8Ø
Sodium bicarbonate may be present in the composition,
generally from about 0.05% to about 3.0% by weight of the
total composition for adjustment of pH.
The soft contact lens wetting or in-eye comfort
drop composition according to the invention preferably
will have a tonicity of from about 1.00 to about 1.45.
Thus, the compositions of the invention are mildly hyper-
tonic to help prevent possible absorption i~to the lens
matrix of foreign matter, bacteria or other residue which
could build up and cause contamination problems and deteri-
oration and discoloration of the lens itself. The remainder
of the composition is purified water U.S.P.
The wetting compositions of the invention con-
taining polyvinyl alcohol, polyvinylpyrrolidone and/or a
cellulosic polymer of the type described are especially
useful for wetting silicone copolymer contact lenses after
the lenses have been cleaned with a nonionic detergent
cleaner suitable for cleaning the lenses,
It has been discovered that the surface charge
or static electricity charge which may be present on
silicone copolymer lenses is eliminated or neutralized by
such nonionic detergents and makes the lenses wettable by
the aforesaid wetting compositions. Failure to eliminate
or neutralize such charges can prevent such lenses from
being adequately wetted.
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Thus, in accordance with another aspect of the
present invention, a method of wetting a silicone copolymer
contact lens having a surface charge is provided that
comprises neutralizing or eliminating the surface charge
and contacting the lens with a wetting composition con-
taining at least one wetting component selected from
polyvinyl alcohol, polyvinylpyrrolidone and a cellulosic
polymer. Suitable wetting components are as previously
described herein. One procedure by which the surface
charge can be neutralized or eliminated is by contact with
nonionic detergent material as aforesaid. The nonionic
detergent material is then rinsed from the lens prior to
wetting. Suitable nonionic detergents include hydro-
xyalkylated and polyoxyalkylated surfactants,
The preferred non-ionic detergents are a combination of a
polyoxypropylene-polyoxyethylene block copolymer, an
amphoteric surface active agent and an alkylaryl polyether
alcohol~ `
12 1256776
DETAILED DESCRIPTION OF THE INVENTION
According to the invention, the preservative
system, which provides antibacterial and antifungal acti-
vity, usually includes from about 0.01% to about 2.0%
trimethoprim, preferably about 0.025% by weight of the
total composition and benzyl alcohol, usually present in
an amount of from about 0.1% to about 5.0% by weight of
the total composition. Trimethoprim is also known as
2,4-Diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidine and as
Syraprim. See, for example, The Merck Index, tenth edition,
pg 1,387.
Other adjuvant bactericides may be present in
the preservative system, such as, for example, from about
0.025% to about 0.5%, preferably 0.1%, by weight of the
total composition of ethylenediaminetetraacetic acid or a
water soluble salt thereof which has bactericidal proper-
ties. The types of bacteria and other organisms to which
the solutions are susceptible to exposure and which are
necessary to protect against are adequately rendered
inactive or killed by the trimethoprim benzyl alcohol and
salts of EDTA.
The inclusion of ethylenediaminetetraacetic acid
or a water soluble salt of ethylenediaminetetraacetic acid
serves as a buffering and preservative component of the
composition according to the invention, and has also been
demonstrated to have antibacterial and antifungal proper-
ties. The preferred salt of ethylenediaminetetraacetic
acid is disodium ethylenediaminetetraacetate (disodium
EDTA or disodium edetate). Other salts of EDTA which may
be utilized include, for example, mono-, di-, tri- and
tetra-alkali metal salts.
Any suitable wetting system can be used in
accordance with the invention. The preferred wetting
system contains a wetting agent and a viscosity-building
-13- ~2~5~7~
agent. An especially preferred wetting system contains
hydroxyethylcellulose, polyvinylpyrrolidone and polyvinyl
alcohol. A preferred hydroxyethylcellulose is available
from Hercules, Inc. of Wilmington, ~elaware under the
trade designation "250 H." A preferred polyvinylpyrro-
lidone is available from GAF Corporation of New York, New
York under the name Plasdone~ C. A preferred polyvinyl
alcohol is available from the Monsanto Company of St. Louis,
Missouri under the T~l of "Galvatol" which is partially
hydrolized.
The wetting compositions of the present inven-
tion are preferably buffered and slightly acid or neutral.
The preferred pH range is from about 7.0 to about 8Ø
Suitable buffers are known in the art. Suitable buffers
include sodium bicarbonate. The preferred combination of
buffers is sodium bicarbonate,-sodium phosphate (tribasic),
sodium biphosphate and sodium bisulfite, in amounts to
provide and maintain the desired pH.
The remainder of the wetting composition is
purified water U.S.P. and the composition preferably
includes combinations of essentially neutral and alkaline
salts compatible with ocular tissue and soft contact lens
material which are water-soluble, generally present in a
concentration to provide an a~ueous composition salt
content equivalent to from about 1.00 to about 1.45 toni-
city. Thus, the soft contact lens cleaning solutions of
the present invention can be mildly hypertonic which helps
in the prevention of possible absorption into the lens
matrix of foreign matter, protein, lipids and bacteria
which could build up and cause contamination problems and
deterioration and discoloration of the lens itself.
Sodium chloride can be present in the soft contact lens
- wetting composition, usually in an amount from about 0.05%
to about 2.0% by weight of the total aqueous composition,
for example, and preferably in an amount of about 0.79% by
12S6776
-14-
weight of the total aqueous composition. Potassium chloride
is another salt which is preferably used in conjunction
with sodium chloride and should generally be present
in an amount of from about 0.05% to about 2.0% by weight
of the total aqueous composition and preferably in an
amount of about 0.368% by weight of the total aqueous
composition.
An especially preferred wetting composition is:
Component Amount (% by weight)
Sodium bicarbonate 0.100
Sodium phosphate (tribasic) 0.030
Component Amount (% by weight)
Sodium biphosphate 0.030
Sodium chloride 0.790
Potassium chloride 0.368
Disodium EDTA 0.100
Hydroxyethylcellulose 250H 0.400
Polyvinyl alcohol 1.000
Polyvinylpyrrolidone (Plasdone~ C) 0.500
Trimethoprim 0.025
Sodium Bisulfite 0.050
~enzyl Alcohol 0.200
Propylene Glycol 0.500
Purified water U.S.P.Balance to 100
While the present invention has been described
primarily with respect to wetting solutions, the wetting
compositions of the invention containing a water soluble
cellulosic polymer, polyvinyl alcohol and polyvinylpyr-
rolidone and preservative system are especially useful for
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application directly into the eyes while contact lenses
are being worn for effective relubrication and immediate
restoration of comfort when applied to eyes which are dry~
tight and/or uncomfortable. Such compositions further
reduce the tendency of oil and mucous deposits to accumu-
late on contact lenses. These compositions are especially
suitable for use with silicone, silicone copolymer contact
lenses and soft contact lenses.
Whereas the present invention has been described
with respect to specific embodiments thereof, it will be
understood that various changes and modifications will be
suggested to one skilled in the art and it is intended
that the invention encompass such changes and modifica-
tions as fall within the scope of the appended clalms.
