Note: Descriptions are shown in the official language in which they were submitted.
~z4~7~1
BACKGROUND OF THE INVENTION
Just as there are marked differences in the struc-
ture and composition of hard and soft contact lenses, there
are also marked differances in the maintenance and care or
treatment of the various types of hard, semi-hard and soft
lenses. While patient care and treatment of hard contact
and uncomplicated or conventional contact lenses is rela-
tively simple and uncomplicated, the proper care and treat-
ment of the newer soft and hydrophilic lenses has proved to
be more complex and time consuming.
The primary differen~e between the conventional
hard contact lens and the more complex soft lenses is the
marked increase in the polar or water attracting centers of
the hydrophilic gel material. 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 diffi-
culties in and disinfecting or asepticising the soft hydro-
philic lens. The hydrophilic nature of soft contact lenses
makes the lenses vulnerable to bacterial contamination.
~Yhile studies have demonstrated that bacteria cannot pene-
trate the actual intramolecular pores of the hydrophilic
lens, except in defective lenses, the bacteria have an
affinity for the protein and tear deposits on the surfaces
of the lens matrix. In particular, the tears and fluids
absorbed in the soft lenses serve as excellent bacterial
culture media. If defects or nicks occur in the lens either
during manufacture or subse~uent patient wear, bacteria may
find a haven to ~row and be sheltered from superficial lens
cleaning and disinfection.
12~474~
Potentially harmful fungi also provide a possible
danger to the soft contact lens. Fungi, like bacteria, can
thrive in tear secretions or deposits and penetrate the lens
material directly if enzymatic degradation of the lens
material has taken place.
Other problems can accrue from incorrect and
careless handling of the soft lenses by the patient himself.
Many potential contaminants and lens deposits can be trans-
ferred from unwashed fingers to the surface of t~e soft
lens. These include oily deposits from the skin, sweat,
skin lotions and creams, mascara, detergents, lipstick and
even nicotine. Controlled studies have demonstrated that
bacterial contaminants occur in 43% of the makeup used by
women, and fungal contaminants in 12%. Attempts to effect
sterilization of the lenses by boiling, for example, can be
cumbersome in addition to causing permanent damage to the
lenses if done improperly. If the patient has used impure
water for storage and rinsing of the lenses, undesirable
deposits such as calcium, iron and insoluble divalent and
trivalent metallic salts as well as other chemical deposits
can collect on the lens surfaces.
Therefore, a need has arisen for an effective
composition to counteract and mitigate the above described
effects of improper hygiene and lens handling as well as to
provide optimum disinfection and storage of the soft lens
between lens wearing periods. In addition, the active
ingredients of an effective contact lens solution should
preferably: l) disinfect clean soft lenses within a period
of four to six hours and produce D values of a 90% kill rate
of microorganisms, selected fungal and yeast organisms, and
viral agents such as herpes simplex; 2) not be easily inac-
tivated by small amounts of proteins, lipids or other tear
and extraneous components and deposits; 3) not bind to
protein-or other lens surface deposits from the eye; and
4) not react with or absorb to the soft lens material or
matrix. For example, several antiseptic agents which meet
the above requirement for rapid and effective kill of a
broad range of microorganisms have proved to be unsuitable
for use in soft lens treatment solutions, in that these
agents are incompatible with the soft lens material or bind
with protein deposits on the surfaces of the lens matrix.
Other antiseptic agents are unacceptable for use in soft
lens solutions since they are concentrated by the lens
material, to the extent that they cause discomort and
potential damage to the corneal surface of the wearer's
eyes. Benzalkonium chloride is one such antiseptic agent
which meets the requirements for the effective and rapid
killing of microorganisms but is unacceptable because it
binds with many types of soft lens material and also binds
with protein deposits on the lens surface.
One type of cold disinfecting solution for soft
contact lenses uses chlorohexidine. However, chlorohexidine
is absorbed by the soft contact lens material and gradually
eluded into the eye often causing excessive burning, irrita-
tion and red eye, in addition to discoloring soft lenses,which can prevent the patient from wearing the lenses.
Therefore, a need has arisen for a highly effec-
tive cold storage and disinfecting solution and method for
the overnight or interim disinfection and storage of soft,
silicone and silicone co polymer contact lenses which meet
the aforesaid requirements.
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SUMMARY OF THE INVENTION
In accordance with the present invention, an
aqueous storage and disinfecting solution containing
trimethoprim and benzyl alcohol for the ambient temperature
or cold storage and disinfection of soft, silicone and
silicone co-polymer contact lenses is provided. More
particularly, the invention provides an effective ambient
temperature storage and disinfecting solution for the
disinfection and storage of hydrophilic gel lenses, (HEMA)
silicone and silicone co-polymer contact lenses, and gelfle~
material soft lenses including, for example, the following
plastic gel materials: Hydroxyethyl methacrylate (HEMA) or
its analogues, ethlene glycol dimethacrylate (EGMA) or its
analogues, silicone and silicone co-polymer contact lenses.
In accordance with the present invention, a method
for treating a contact lens is provided to kill bacteria
that may be associated with the lens which method comprises
contacting the lens with an aqueous composition c~ntaining
trimethoprim and benzyl alcohol present together in an
effective concentration for killing bacteria. The method is
especially suitable for treating soft, silicone and silicone
co-polymer contact lenses. No heat disinfecting is required
and therefore, problems associated with elevated ~emperature
treatment are eliminated.
The aqueous composition in accordance with the
invention contains trimethoprim and benzyl alcohol present
together in an effective amount of concentration for killing
bacteria. Generally, an effective concentration o trime-
thoprim is from about 0.01% and 4.0% by weight of the total
composition. Generally, an effective amount of benzyl
alcohol whic~ acts as an adjuvant bactericide is from about
0.10% to about 5.0% by weight of the total composition. The
combination of trimethoprim and benzyl alcohol provides an
ambient temperature disinfecting solution that is effective
-" ~LZ44~41
in killing microorganisms, fungal organisms and viral agents
such as herpes simplex. Generally, benzyl alcohol is present
in an amount of from about 0.10% and about 5.0% by weight of
the total composition. In addition, another important
function of benzyl alcohol is to facilitate the dissolution
of trimethoprim in the aqueous composition, thereby making
it more feasible to utilize trimethoprim.
A salt of ethylenediaminetetraacetic acid may be
included as a buffering agent and to provide increased
bactericidal properties. Other buffering agents may also be
present as hereinafter described.
The remainder of the composition may comprise
solely water or may include various alkaline metal and
alkaline earth metal water soluble salts to provide an
aqueous composition salt content equivalent to about 0.8%
to about 1.8% sodium chloride by weight of the total
aqueous composition. A humectant such as propylene glycol
may be optionally included in the composition.
~ ~47~L
DETAILED DESCRIPTION OF THE INVENTION
The aqueous ambient temperature disinfecting
compositions for soft, silicone and silicone co~polymer
contact lenses of the present invention contain trimethoprim
and benzyl alcohol. The compositions in accordance with the
invention act as a disinfectant for contact lenses without
the necessity for heat disinfecting. The compositions are
particularly useful for disinfecting soft, silicone and
silicone co-polymer contact lenses, and can also be used
with hard lenses. As used herein, the term "disinfectant"
means a substance that destroys or kills bacteria, fungi,
yeasts or viruses.
Trimethoprim and benzyl alcohol are present to-
gether in the composition in a concentration sufficient to
provide a disinfectant solution for soft contact lenses.
Generally, an amount of trimethoprim of from about 0.01% to
about 4.0% by weight of the total composition and an amount
of benzyl alcohol of from about 0.10% to about 5.0% by
weight of the total composition are sufficient concentra-
tions to provide a disinfectant solution for soft contactlenses. 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, page 1387. Prefer-
ably, trimethoprim is present in an amount of about 0.1~5%
by weight of the total composition and benzyl alcohol is
present in an amount of about 2.0% by weight of the total
composition.
In order to further enhance the disinfectant
properties of the composition in accordance with the present
invention, ethylenediaminetetmaacetic acid (EDTA) or a water
soluble salt of ethylenediaminetetraacetic acid that has
disinfectant properties is preferably present in an effective
amount for enhancing the D value kill factor relating to
bacteria, fungus, yeast and/or viral organisms. A preferred
` ~4~7~
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salt of EDTA is the disodium salt (disodium edetate). Other
salts of EDTA which may be utilized include, for example,
mono-, di-, tri- and tetra-alkali metal salts. Generally,
an effective amount of EDTA or salt thereof is from about
0.025% to about 0.5% by weight of the total composition.
Preferably, disodium edetate is present in an amount of
about 0.25% by weight of the total composition.
The compositions of the present invention prefer-
ably include at least one essentially neutral water-soluble
compatible salt to provide tonicity equivalent to between
about 0.8% and 1.8% sodium chloride by weight of the total
aqueous composition. Thus, the preferred compositions
according to the invention provide a tonicity which is about
the same as or slightly higher than the tonicity of normal
human tear fluid. While hypertonic solutions can be desir-
able since the solution will have a greater osmotic pressure
than that of the tear fluid of the contact lens wearer, any
soluble salts or mixtures of salts, compatible with ocular
tissue, can be used to provide the desired tonicity. Pre-
ferably, sodium chloride, potassium chloride or mixturesthereof, are used to provide the desired tonicity. It is
undPrstood, however, that one or more essentially neutral,
water-soluble alkali or alkaline earth metal salts can be
substituted in whole or in part or the sodium or potassium
chloride in the solutions of the invention, when tonicity
adjustment is desired. Preferably, sodium chloride and
potassium chloride are utilized in weight ratio of from
about 2:1 to about 7:3, respectively.
Preferably, a buffer or buffers are present in the
composition. Suitable buffers are known in the art and
include, for example, buffers such as sodium bicarbonate.
The preferred combination of buffers is sodium bicarbonate,
sodium phosphate (tribasic), sodium bisulfit~ and sodium
biphosphate, present in amounts to provide and maintain the
desired pH.
47~
Propylene gl~col may optionally be included in the
compositions, generally in an amount of from about 0.2% to
about 2.5% by weight of the total aqueous composition and
preferably in an amount of about 1.0% by weight of the total
aqueous composition. The propylene glycol acts as a humectant,
preservative and fungal growth inhibitor.
The balance of the composition is purified water
U . S . P .
In accordance with one embodiment of the present
invention, a treatment method is provided for killing bac-
teria associated with contact lenses. A contact lens is
treated by storing the lens in an aqueous solution contain-
ing trimethoprim and benzyl alcohol present together in an
effective concentration for killing bacteria. Any of the
solutions in accordance with the invention can be used. The
lens is brought into contact with an aqueous composition in
accordance with the invention for a period of time sufficient
for the composition to kill at least a portion of the bacteria
associated with the contact lens. For example, the lens is
introduced into a container having a solution in accordance
with the invention generally after proper cleaning procedures
are followed in an amount sufficient to completely immerse
the lens. The container is then closed and the contact lens
is allowed to remain in the solution for a time sufficient
to disinfect the contact lens. No external source of heat
is applied and thus, the lens is stored at ambient temperature.
Generally, storing the lens in a solution in accordance with
the invention for about six hours will provide sufficient
disinfection of the contact lens or bacteria for wearing the
lens. Thus, the method is ideal for overnight storage of
contact lenses or storage between wearing periods. However,
it is anticipated that for some solutions in accordance with
the invention, less than six hours of storage will be sufficient.
- In accordance with the method of the invention,5 heating of the solution or lens is not required. Thus, the
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solutions and method of the present invention allow the lens
to be disinfected at ambient temperature, eliminating possi-
bility of deleterious effects that may occur when the lens
is heated.
The aqueous composition in accordance with the
invention is preferably utilized as part of the total patient
regimen for maintaining and treating soft, silicone and
silicone co-polymer contact lenses. Thus, an effective
cleaning step or steps is an important part of any effective
soft or firm lens treatment and maintenanc`e regimen.
Separate cleaning of the lenses insures that the disinfectant
properties of the aqueous solution will not be overwhelmed
by gross organic or inorganic deposits and pollutants.
An especially preferred rinsing and cold disin-
fecting solution is:
Component Amount (yO by weight)
Sodium bicarbonate 0.100
Sodium phosphate (tribasic) 0.030
Sodium biphosphate 0.030
20 Sodium chloride 0.790
Potassium chloride 0.368
Disodium EDTA 0.~50
Trimethoprim 0.125
Sodium bisulfite 0.050
25 Component Amount (/ by weight~
Ben~yl alcohol 2.000
Propylene glycol 1.000
Purified water U.S.P. Balance
Whereas the present invention has been described
with respect to specific embodiments, 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 modifications as fall within the
scope of the appended claims.
