U.S. patent number 3,920,810 [Application Number 05/463,273] was granted by the patent office on 1975-11-18 for polyacrylamide containing ophthalmic solutions.
This patent grant is currently assigned to Burton, Parsons and Company, Inc.. Invention is credited to Billy F. Rankin.
United States Patent |
3,920,810 |
Rankin |
November 18, 1975 |
Polyacrylamide containing ophthalmic solutions
Abstract
An ophthalmic solution is provided for treatment of "dry eye,"
providing lubricating and cushioning effects for traumatized eyes,
including trauma caused by the wearing of hard of gel-type contact
lenses, and as a carrier for ophthalmic medicaments. The solution
is an aqueous solution of polyacrylamide optionally and preferably
including polyethylene glycol, and other optional ingredients.
Inventors: |
Rankin; Billy F. (Rockville,
MD) |
Assignee: |
Burton, Parsons and Company,
Inc. (Washington, DC)
|
Family
ID: |
25769044 |
Appl.
No.: |
05/463,273 |
Filed: |
April 23, 1974 |
Current U.S.
Class: |
424/78.04 |
Current CPC
Class: |
A61K
9/0048 (20130101) |
Current International
Class: |
A61K
9/00 (20060101); A61K 031/79 (); A61K 031/78 () |
Field of
Search: |
;424/78,80,81 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Cofholm, Handbook of Non-Prescription Drugs, (1973) pp.
99-107..
|
Primary Examiner: Drezin; Norman A.
Attorney, Agent or Firm: Fidelman, Wolffe & Leitner
Claims
What is claimed is:
1. An ophthalmic solution comprising an aqueous solution of a water
soluble polyacrylamide polymer, having a molecular weight of at
least about 75,000, in an amount of from about 0.05 to 20 weight
percent sufficient to provide a viscosity of from about 0 to 30,000
cps and from about 100 to about 5000 weight percent, based on the
polyacrylamide polymer, of a polyalkylene glycol selected from the
class consisting of polyethylene glycol and polypropylene glycol
having a molecular weight of from about 400 to 6000.
2. The composition of claim 1 wherein said polyacrylamide polymer
has a molecular weight of about 200,000 to 10,000,000.
3. The composition of claim 1 wherein said polyacrylamide polymer
has a molecular weight of about 5 to 6,000,000.
4. The composition of claim 1 wherein said polyalkylene glycol is
polyethylene glycol.
5. The composition of claim 4 wherein said polyethylene glycol has
a molecular weight of about 4,000.
6. The composition of claim 1 wherein said aqueous solution further
comprises, a material selected from the group of (1) eye compatible
acids in an amount to maintain the pH of the solution at from about
3 to about 7, and (2) eye compatible pH buffers in an amount
sufficient to maintain the pH of the solution at from 7.4 to about
8.2.
7. The composition of claim 6 wherein said acid is boric acid.
8. The composition of claim 6 wherein said buffer is a combination
of mono-sodium and di-sodium phosphates.
9. The composition of claim 1 wherein said aqueous solution further
comprises a mechanical buffer selected from the group consisting of
methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,
carboxymethyl cellulose, hydroxypropyl methyl cellulose and
mixtures thereof.
10. The composition of claim 1 wherein said aqueous solution
further comprises up to about 0.5 percent by weight of an eye
compatible non-ionic surfactant.
11. The composition of claim 1 wherein said aqueous solution
further comprises up to about 5 percent by weight polyvinyl
pyrrolidone.
12. An ophthalmic solution comprising an aqueous solution of a
polyacrylamide, having a molecular weight of at least about 100,000
in an amount of from about 0.05 to 20 weight percent sufficient to
provide a viscosity of from about 0 to 30,000 cps. and a material
selected from the group of (1) eye compatible acids in an amount to
maintain the pH of the solution at from about 3 to about 7, and (2)
eye compatible pH buffers in an amount sufficient to maintain the
pH of the solution at from about 7.4 to about 8.2.
13. The composition of claim 12 wherein said material is boric
acid.
14. The composition of claim 12 wherein said buffer is a
combination of monosodium and disodium phosphates.
15. The composition of claim 12 wherein said aqueous solution
further includes a mechanical buffer selected from the group
consisting of methyl cellulose, hydroxyethyl cellulose,
hydroxypropyl cellulose, carboxymethyl cellulose, hydroxypropyl
methyl cellulose, and mixtures thereof.
16. The composition of claim 12 wherein said aqueous solution
further includes up to about 0.5% by weight of an eye compatible
non-ionic surfactant.
17. The composition of claim 12 wherein said aqueous solution
further includes up to about 5% by weight polyvinyl
pyrrolidone.
18. A method of treating the human or animal eye to provide a
synthetic mucous membrane layer to serve as a wetting, cleaning,
lubricating and cushioning agent, which comprises adding thereto an
effective amount of an ophthalmic solution comprising an aqueous
solution of a polyacrylamide polymer, having a molecular weight of
at least about 100,000, in an amount from about 0.05 to 20 weight
percent sufficient to provide a viscosity of from about 0 to 30,000
cps.
Description
The present invention relates to a multi-functional ophthalmic
solution designed for and adapted to general use in the eyes of
humans and domestic animals. The present invention further relates
to the provision of a synthetic mucous layer which serves as a
wetting agent in the eye, i.e. an artificial tear material useful
for the treatment of both "dry eye" or as a cleaning, lubricating
and cushioning agent for the eye after an injury or therapeutic
surgery. The invention also relates to the utilization of the
ophthalmic solution as a carrier for ophthalmic medicaments. Still
further, the invention relates to an ophthalmic solution useful as
a cleaning, lubricating and cushioning agent for both hard and
gel-type contact lenses. The invention also relates to the
attainment of all the foregoing functions without optical
interference and with a solution which may be readily buffered to
any convenient pH. The invention further relates to an ophthalmic
solution having bactericidal activity.
Heretofore, ophthalmic solutions have generally conformed to the
general specifications required for all such intended utilizations
in the treatment of the eye. Such solutions have generally been
isotonic, buffered to the required pH, sterile and have contained
additives for improved viscosity and longer retention in the eye.
However, with many of such solutions, the problems of dosage,
irritation to the eye, stability and occular response persist.
Many attempts have been made to resolve these problems by modifying
existing formulas, using different forms of eye-treating
substances, or using bases immiscible with aqueous solutions. Such
attempts have added little to the performance qualities of the
products.
It is accordingly an object of the present invention to provide a
multipurpose opthalmic solution, suitable for general utilization
in the eye of both humans and domestic animals.
A further object of the present invention is the provision of such
solutions which can be readily modified for particular purposes and
utilizations, including the introduction into the eye and the
retention therein, of opthalmic medicaments, the provision of a
wetting agent which serves as an artificial tear for the treatment
of "dry eye," or a cushioning or lubricating agent for an injured
or surgically treated eye, as a cleaning, lubricating and
cushioning agent for utilization in conjunction with both hard and
gel-type contact lenses and the like.
These and still other objects, as will become apparent from the
following disclosure, are attained by the composition of the
present invention which, in its broadest terms, comprises a
polyacrylamide polymer having a molecular weight of from about
75,000 to about 10,000,000, water, and optionally, a polyalkylene
glycol, preferably polyethylene glycol or polypropylene glycol, and
having a molecular weight of about from 400 to 6,000.
Polyacrylamide are known to exhibit excellent lubricating
characteristics in aqueous solution and are freely soluble in water
without degradation. Wide ranges of molecular weights are
available. In the present invention, these can be from 75,000 up to
several million, e.g. 10,000,000 or even greater. The medium
molecular weight materials are preferred in the present invention
and a range of 250,000 to 6,000,000 has been found particularly
useful. Most preferred is a polyacrylamide having a molecular
weight of about 5,000,000. Such resins have extraordinary
thickening action in water, even in the presence of salts. The
thickening power increases sharply with both concentration and
molecular weight. Thus, to attain the desired viscosity,
substantially less polyacrylamide polymer is required for a
relatively higher weight that would be the case when a lower
molecular weight polymer is utilized. In addition, the higher
molecular weights result in a higher strength lubricating film in
solutions due to orientation of polymer will vary in the present
invention with the molecular weight to provide a viscosity of from
0 to about 30,000 cps at 20.degree.C. as measured by Brookfield
Viscosimeter, where viscosities of from 0 to about 200 cps are
measured using the ultra-low viscosity adapter rotated at a speed
of 0.6 rpm, and viscosities greater than about 200 cps are measured
with a number 6 spindle rotated at 10 rpm. Such viscosities will
ordinarily be obtained when the concentration is within the range
of about 0.05 to 20.0 weight percent, often preferably about 0.1 to
5.0 weight percent, depending upon the molecular weight of the
polymer employed. With lower viscosities (whether due to lower
molecular weight polymers or lower concentration, or both) inferior
lubrication results. Higher viscosities result in difficult
handling properties and characteristics, including insufficient
flowability for fully effective utilization in the eye.
As used in the present disclosure, the term polyacrylamide is used
to refer to homopolymers obtained by the addition polymerization of
acrylamide, and is limited to such materials having a molecular
weight of at least about 25,000, preferably at least about 100,000,
ranging up to as much as 10,000,000 or more. The polymers of
interest are generally linear, N-unsubstituted materials, and are
per se well known to those of ordinary skill in the art, and are
widely available commercially. Such polymers are formed by numerous
addition polymerization techniques, usually by those involving the
employment of free radical catalyst systems.
The polymers are water soluble, meaning that the polyacrylamides
form true solutions in pure water, free of gel particles, and are
infinitely dilutable with water.
Aqueous solutions of the polyacrylamide resins have a low level of
oral toxicity and an extreme level of compatability in contact with
the skin or in the eye. They are also characterized by a high level
of pituitousness and an extraordinarily high degree of
pseudo-plasticity. The solutions are highly stable through a wide
range of temperatures and can tolerate extremely wide variations in
pH.
Because of the strong hydrogen bonding affinity of the amide group
in the polyacrylamide chain, the resin solutions will form
association complexes with a wide variety of materials. Such
association complexes per se often exhibit properties markedly
different from either component alone, but it has been found that
the resin will give up associated materials when introduced into
the eye. The dissociation in vivo may result from a salting out
effect produced by the materials with which the solutions are
contacted, e.g., various salts occuring in tears and the like.
Because of the high levels of pseudo-plasticity and pituitousness
of polyacrylamide aqueous solutions, it is highly desirable to
include in the solution a material which will render a plasticizing
effect. In addition, it is also desirable to include a humectant
which will enhance fluid retention over the course of long term
usage in the eye. These functions are provided by the inclusions in
the solution of a polyalkylene glycol. The preferred polyalkylene
glycol is polyethylene glycol, such as the Carbowaxes, as supplied
by Carbide and Carbon Chemicals Company. Such materials have
molecular weights ranging from about 400 up to as much as about
6000. Particularly preferred in the compositions of the preferred
invention is polyethylene glycol having molecular weight of about
400, although this preference is primarily because of the ready
availability and convenience of processing of the particular
material. Polyglycols containing other alkylene groups can be
utilized, such as polypropylene glycol and the like, but such
materials are often not as readily available, and for this reason
alone are not particularly preferred in the present invention. The
polyalkylene glycol can be present in amounts ranging up to 5000,
preferably 500 to 5000, weight percent based on the weight of the
polyacrylamide polymer. Less than about 100% by weight can
occasionally result in insufficient water retention and
plasticizing effect, with concomittent drying of the eye and
irritation of occular tissue, while amounts greater than about
5,000 weight percent can exhibit a "salting out" effect, with the
formation of waxy solid globules or particles which be irritating
to occular tissue.
The basic opthalmic solution of the present invention, i.e., the
aqueous solution of polyacrylamide and polyalkylene glycol, is
useful per se in a number of contexts. Primary among these is the
provision of a synthetic mucous layer, which serves to clean and
lubricate the eye, serving as a wetting agent and artificial tear
for the treatment of "dry eye" or to provide a cushioning effects
attained when the solution of the present invention is used in
conjunction with contact lenses, of both the hard resin and
gel-type contact lenses, and accordingly, the use of the solution
will be discussed with particular reference thereto.
The advent of the gel contact lens has generated entirely new
requirements for contact lens treating solutions and entirely new
problems in hygenic handling and care for the lenses. In contrast
to the more common hard type lens, usually made of
polymethylmethacrylate, the gel lens will absorb relatively large
proportions of water to form a soft, pliable material which has a
tendency to fray. The gel is a three-dimensional lattice formed by
the polymerization of glycol esters and diesters of acrylic acids.
The glycol moieties of the molecules imparts a strong hydrophilic
character to the lattice, with the consequent ability to absorb
rather large amounts of water. by utilizing the unique properties
of these lenses, new therapeutic options are presented for the
treatment of occular debilities. Since the lens per se represents
only the environment of use of the composition, a more complete
discussion of its physical parameters need not be repeated here. A
discussion of the gel contact lens, including both the preparation
and use thereof occurs in Augenoptika, Heft 6, 1965, pages 5 and 6,
Vienna, Austria, which reports a paper delivered by Maximillian
Dreyfus at the 15th WVA annual meeting.
One characteristic peculiar to the gel lens is the requirement that
treating solutions contain no component that can become entrained
in the lattice of the gel, since such materials tend to accumulate
and become irritating to the occular tissue. The lens does,
however, require a cleaning and lubricating solution to cushion the
occular tissue from direct contact with the lens. The requirement
for a cleaning action is shared by the gel-type lens with hard
lenses and with synthetic tears and other such opthalmic solutions.
The exposure of the eye to various atmospheric pollutants, such as
smoke, dust, pollen, noxious and irritating gases and the like can
create severe discomfort and irritation, particularly in situations
where the pollutants collect in the natural or artificial tear film
to persist for substantial periods of time to exert their
initiating effects. In addition to avoidance of materials which can
accumulate in the gel, the materials must be compatible with the
gel and with occular tissue and not interfere with the
physio-chemical balance of the precorneal films. The attainment of
these objectives is illustrated by the following example:
EXAMPLE I
A polyacrylamide polymer having a molecular weight of about 250,000
(American Cyanamid Company Cyanamer P26) and polyethylene glycol
having a molecular weight of about 4,000 (Carbowax 4000) are
dissolved in distilled water in the following proportions:
Polyethylene Distilled Sodium glycol Polyacrylamide water chloride
______________________________________ 9.00 gms 0.30 gms 300.00 ml
2.55 gms. ______________________________________
The solution is utilized to clean and hydrate gel-type contact
lenses by immersing each lens in sufficient of the solution to
completely cover the lens. Full hydration is effected in about 60
minutes. At the end of the immersion, the lens is lightly rubbed
between the fingers and rinsed with water. Each lens is examined
and was found to be fully hydrated and optically clear. The lenses
are then implaced in human eyes in conventional fashion and are
left in place for periods of 12 to 17 hours without noticeable
irritation. In dry environments or drafts, some subjects flush the
lenses while in place with small increments of the solution (which
is found to effectively clean and rehydrate the lenses), whereby
the tolerance period of the subject is enhanced and any drying
problem alleviated.
By comparison, conventional lens wetting solutions of types
commercially available are found to provide inferior cleaning and
the ingredients occlude in the lens and cause irritation of the
occular tissues.
In addition to the foregoing tests, both the solution of the
present invention and the commercially available lens solution of
U.S. Pat. No. 3,171,752 were tested for retention in the eye in the
following fashion:
A minor amount of fluorescein dye was incorporated into each
solution. One solution was placed in one eye, the other solution in
the other eye, of a number of rabbits. Examination of the eyes
using an ultra-violet light source gave a quantitative base measure
of the amount of solution present. Periodic repetitions of the
examination revealed that this solution was gradually lost in
either case, but that the commercial solution was retained much
less effectively. The eyes treated with the solution of this
example retained at one and one-half hours the same amount of
solution as did the eyes treated with the commercial solution at
twenty-five minutes. Details of the fluorophotometric determination
can be found in Waltman et al. Investigative Ophthalmology, Vol. 9,
No. 4, pp. 247-249, April, 1970.
In no case, including both the utilization of the gel-type contact
lens in the human eye or the solution alone in the eyes of test
rabbits, was any evidence of irritation of the eye found to result
from the solution of the present example.
In addition to the per se usefulness of the ophthalmic solution of
the present invention as illustrated in the foregoing Example I,
the ophthalmic solution of the present invention finds an
additional area of broad utility as a carrier for ophthalmic
treating materials such as medicaments (particularly those
requiring an acid pH). The high effectiveness of the ophthalmic
solution of the present invention is believed due to the strong
ionic bonding affinity of the amide group of the chain. When
combined with the ophthalmic solution of the present invention,
ophthalmic medicaments are found to exhibit a much greater
retention on orbital tissue and results in a longer duration of
medicament activity. In addition, the degree of retention attained
permits the use of smaller amounts of the eye treating substances
than has been found heretofore possible while maintaining the
necessary levels of effectiveness. Examples of medicaments with
which the carrier can be used are:
Pilocarpine, HC1
Hydrocortisone USP (alcohol)
Hydrocortisone Acetate
Prednisolene Acetate and other cortisones
Neomycin Sulfate
Bacitracin
Penicillin
Sulfamerazine
Sodium sulfacetamide
Sulfadiazine
Sulfasoxozone and other sulfa derivatives
Scopolamine hydrobromide
Epinephrine bitrartrate
Phenylephrine HC1 or other derivatives
Prostigmin bromide
Pilocarpine (any of the salts)
Idoxuridine
Antipyrine
Naphthazoline HC1
Antazoline phosphate
The foregoing list is intended to merely exemplary. As the list
illustrates, the opthalmic solution of the present invention can be
utilized as a carrier for substances such as antibiotics,
mydriates, miotics, antihistamines, and the like. The amount of eye
treating substances used with the composition of the present
invention depends upon the nature of this substance or substances
employed and the response of the individual receiving treatment.
Typically, up to 500% or even more, based on the weight of the
polyacrylamide, of the eye treatment medicament can be used.
When the eye treating substance or substances are those requiring
an acid pH, one or more acids can be present in amounts sufficient
to maintain the solutions at a pH of less than 7 and as low as
about 3. An example of an acid which can be used with eye treating
substances such as medicaments requiring an acid pH is boric acid.
However, many eye treating substances must be maintained in a basic
or neutral medium. In these instances, one or more pH buffers such
as sodium borate is added to maintain a solution of a neutral or
slightly basic pH. Typically, the buffering substances present in
an amount sufficient to maintain the pH at the desired level are
from between about 7.4 and about 8.2, and preferably at about 7.6.
Other buffering compositions can be used as well, including a
combination of phosphates such as, for example, monosodium
phosphates and disodium phosphate to provide both acid and base
control. Other photphates, acetates and carbonates can be
substituted for the phosphates mentioned above -- provided they are
compatible with the eye. Specifically, the amount of buffering
additions can range from about 0 to 4%, preferably about 0.2% for
the dibasic component, and from about 0 to about 0.5% for the
mono-basic component, wherein the percentages are by weight based
upon the total weight of the overall composition, with the ratio of
components balanced to provide proper pH for the overall
composition.
The utilization of the opthalmic solution of the present invention
as the carrier for the opthalmic medicaments is illustrated by the
following example:
EXAMPLE II
The following composition is illustrative of the utilization of the
composition of the present invention as a carrier for medicaments:
a polyacrylamide polymer having a molecular weight of about
5--6,000,000 (American Cyanimid Company Cyanamer cyanamer P250),
and a polyethylene glycol having a molecular weight of about 4,000
(Carbowax 4000) are dissolved in distilled water in the following
proportions:
Polyethylene glycol 9.00 gm Polyacrylamide 0.30 gms Distilled water
300.00 ml
To the base solution, there are then added 6.00 gm of pilocarpine
HC1 and 3.00 gm of boric acid. Both the salt and the acid dissolve
readily in this solution.
The foregoing formulation is utilized in the treatment of glaucoma
patients who had previously required four standard pilocarpine
treatments per day. It is found that three treatments with the
formulation of the present invention provides the same therapeutic
effects as the four standard treatments. Studies on normal eye of
both animals and humans, after the fashion indicated in Example I,
showed no adverse effects after prolonged application periods, and
a much longer period of retention in the eye for each
application.
Whatever the contemplated utilization of the opthalmic solution of
the present invention, it can be desirable to include in the
solution one or more of a variety of secondary additives as
hereinafter described in fuller detail. For example:
Highly compatible cellulose derivatives of a variety soluble in
water, such as for example, methyl cellulose, hydroxyethyl
cellulose, hydroxypropyl cellulose, carboxylmethyl cellulose,
hydroxypropyl methyl cellulose and the like, can be included in the
solution to act as a mechanical buffer or as a viscosity control
agent. These can also be used to maintain the viscosity of the
overall composition within the desired range as hereinbefore
described. Specifically, the cellulose derivatives when employed
employed should be present in an amount sufficient to maintain
viscosity of the overall composition at the desired level.
The composition of the invention can also contain one or more eye
compatible biocides, such as thimerosal (sodium
ethylmercurithiosalicylate), and the di-, tri-, or tetrasodium
ethylenediamine tetraacetates. The percentages of such biocides can
vary over a broad range, but typically do not exceed about 1% by
weight of the overall composition.
In addition, the composition of the present invention can also
contain one or more eye compatible non-ionic surfactants in amounts
varying over a wide range (but typically in amounts up to about
0.5% by weight) in order to provide product stability. An example
of the surfactants which can be utilized are Tergitol 1559 (Carbide
and Carbon Chemicals Co.) Pluronic F68 (Wyandotte Chemical Corp.,
Michigan Alkali Division); Tweens of H.L.B. value of 11 or higher
(Atlas Powder Company).
Still another subsidiary component which can be added to the
opthalmic solutions of the present invention includes polyvinyl
pyrrolidone (such as Plasdone C, supplied by Entira Chemicals,
division of GAF Corp.) which performs a number of desirable
functions. Polyvinyl pyrrolidone (PVP) acts as a detoxicant,
binding anti-toxins present in eye fluids and rendering them
harmless. PVP also acts to protect the solution by preventing its
breakdown because of particle agglomeration and acts as a demulcent
lubricant by a combination of adhesive and lubricating properties
which aid in the spreading of the viscous solution. The PVP also
operates to prevent blepharospasm (involuntary eyelid contraction),
but has little effect on an overall composition viscosity. PVP is
desirably present in an amount of from 0.5 to 10.0 weight percent
based on the overall solution.
The foregoing illustrations of secondary additives for the
ophthalmic solution of the present invention are intended to be
merely exemplary of the more common of the additives to ophthalmic
solutions well known to those of ordinary skill in the art. It
should accordingly be understood that such additives are not
required for effective operation of the ophthalmic solution of the
present invention, nor is it intended by the enumeration of certain
additives to exclude others.
While the ophthalmic solution of the present invention is readily
formed by simply combining the ingredients, the polyacrylamide
material can occasionally present difficulties in readily
dissolving due to the formation of lumps. such difficulties can be
avoided by the utilization of the following technique:
an increment of distilled water sufficient to dissolve the
constituents of the composition is placed in a stainless steel
container and heater to about 50.degree.C. If a surfactant is
included in a composition, it is dissolved first in distilled water
by agitation, e.g. with a dispersing mixer which has a variable
speed control set at low speed.
Any medicament (such as pilocarpine HC1, pH buffers) and the
polyalkyline glycol (such as Carbowax 4000) and other additives
(such as biocides and the like) are then dissolved with medium
speed agitation in the water/surfactant mixture, following which
the polyvinyl pyrrolidone is added with high-speed mixing and
agitation. If a cellulosic derivative mechanical buffer is
utilized, it is sifted slowly into the vortex created by the
agitator at high speed. When the cellulosic substance is completely
dispersed, the polyacrylamide is sifted slowly into the vortex at
high agitation, until the resin appears to be climbing up to
agitator shaft, at which time the speed is reduced to 100 to 200
rpms. Agitation is then continued until the resin is completely
dissolved in the solution, typically from 2 to 6 hours. Additional
distilled water is then added to bring the solution up to volume.
When some components are temperature sensitive, the product may be
sterilized after packaging by means of ethylene oxide gas
sterilization. Containers for the solution are placed in racks in a
gas autoclave, which draws a vacuum of about 24 ml of mercury,
after which all air is replaced with an ethylene oxide-freon
mixture (12-88%) at 12 psi for 12 hours and at relative humidity of
45 to 50%. It is also possible to sterilize in an autoclave if the
conditions are controlled to minimize thermal damage to any
sensitive ingredients.
EXAMPLE III
As an illustration of the composition of the present invention
containing the aforementioned secondary additives, the following
composition was prepared on a relatively large scale:
bacteriocide (Thimerosal, 10%) 240 cc disodium phosphate 1200 gms
polyethylene glycol (MW. 4,000) 6000 gms polyvinyl pyrrolidone 3000
gms disodium ethylenediamine- tetracetate 600 gms non-ionic
surfactant 132 gms hydroxy ethyl cellulose (MW 52,000) 3000 gms
polyacrylamide (Cyanamer P250) 3000 gms distilled water 150
gallons
The solution formed from the foregoing components was clear and
free of polymer globules and was found to have a pH of about 7.3
and a viscosity of about 150 cps.
The solution was utilized as a wetting, cleaning and cushioning
medium by a number of patients using hard-type, polymethyl
methacrylate contact lenses. With patients who had previously worn
the lenses, greater comfort and tolerance were reported, even by
those who had previously experienced difficulty with the lenses.
Most patients reported that they were able to wear their lenses for
greater periods of time than had previously been possible,
regardless of the type of wetting solution they had used before.
With patients who had not previously worn contact lenses, the
solution of the present invention dramatically reduced the problems
of lens delivery and greatly accelerated the adaptation of the
patients to the use of the lenses. In all the trials, no adverse
side effects or irritation was noted either subjectively or by
clinical examination.
It has been noted that in the utilization of the opthalmic solution
of the present invention with contact lenses, certain ranges of
viscosity provide better results than others. For example, with
hard-type lenses, the best results are attained at a viscosity of
about 30 to 200 cps and that range is accordingly preferred for
such usage. The most preferred viscosity for the use with hard-type
lenses is about 150 cps. With the gel-type lens, the most effective
(and hence the preferred) viscosities lie in the range of about 0
to 30 cps, with values of about 10 being most preferred. No
variation of effectiveness with viscosity has been noted when the
solution is used as a carrier for medicaments or as a synthetic
tear or the like.
It should be noted that a viscosity of zero as measured is a result
of the limitations of the available techniques and apparatus and
does not represent such an anomaly as it might superficially
appear. It should be further noted that all designations of
viscosity appearing herein represent the values as obtained with
the Brookfield Viscosimeter where all values below 100 are obtained
with the ultra-low viscosity adapter rotated at 0.6 rpm and all
values above 200 are obtained with a number 6 spindle at 10 rpm.
For values ranging from about 175 to 250 cps, results obtained by
the two differing adaptations are generally comparable in the case
of the present solutions.
A further example of the effectiveness of the composition of the
present invention occurs primarily in the area of ophthamologic
diagnosis, where it is conventional to apply fluorescein or a
comparable material, dissolved in a carrier, to the eye. After
allowing the dye to penetrate the tissues of the eye, an
examination is conducted by visual inspection with the aid of an
ultra-violet light source, which causes the dye to fluoresce. It
has been found that when the opthalmic solution of the present
invention is utilized as the carrier, the dye is absorbed in
substantially greater proportions and at a much faster rate than
has been possible with the compositions of the prior art.
Accordingly, solutions, of fluorescent dyes in the opthalmic
solution of the present invention are of great aid in the
examination of the eye.
While certain specific considerations have been disclosed and
discussed herein, such have been offered solely to exemplify the
present invention and should in no way be constructed as limiting.
The proper scope and nature of the invention is set forth in the
following claims.
* * * * *