U.S. patent application number 13/112549 was filed with the patent office on 2011-09-15 for ophthalmic composition.
Invention is credited to Kazuhiro Fukushima, Yasuko MATSUMURA.
Application Number | 20110223126 13/112549 |
Document ID | / |
Family ID | 40452041 |
Filed Date | 2011-09-15 |
United States Patent
Application |
20110223126 |
Kind Code |
A1 |
MATSUMURA; Yasuko ; et
al. |
September 15, 2011 |
OPHTHALMIC COMPOSITION
Abstract
The present invention provides an ophthalmic composition which
stabilizes the tear film during wearing contact lens, prevents eye
dryness, imparts a favorable sensation in using, is highly
convenient with no risk of misuse and shows a high efficiency in
the course from manufacturing to sales. More specifically, the
present invention provides a wetting solution--eye drops for
contact lenses comprising (A) one or more member(s) selected from
the group consisting of a cellulose-based polymer, a vinyl-based
polymer, polyethylene glycol and dextran; and (B) a terpenoid.
Inventors: |
MATSUMURA; Yasuko;
(Osaka-shi, JP) ; Fukushima; Kazuhiro; (Osaka-shi,
JP) |
Family ID: |
40452041 |
Appl. No.: |
13/112549 |
Filed: |
May 20, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12678063 |
Mar 12, 2010 |
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PCT/JP2008/066416 |
Sep 11, 2008 |
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13112549 |
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Current U.S.
Class: |
424/78.04 |
Current CPC
Class: |
A61K 31/74 20130101;
A61P 27/04 20180101; A61P 27/02 20180101; A61K 9/0046 20130101;
A61P 43/00 20180101; A61K 31/125 20130101; A61K 31/717 20130101;
A61K 31/045 20130101; A61K 31/721 20130101; A61F 9/0061
20130101 |
Class at
Publication: |
424/78.04 |
International
Class: |
A61K 31/78 20060101
A61K031/78; A61P 27/02 20060101 A61P027/02 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 14, 2007 |
JP |
2007-239049 |
Feb 8, 2008 |
JP |
2008-028985 |
Claims
1. A method of using a composition comprising (A) one or more
member(s) selected from the group consisting of a cellulose-based
polymer, a vinyl-based polymer, polyethylene glycol and dextran;
and (B) a terpenoid as a wetting solution--eye drops for contact
lenses, said method comprising successively (i) adding said
composition directly to a contact lens dropwise in order to wet
said contact lens before fitting said contact lens, (ii) fitting
said contact lens to an eye, and (iii) wetting said contact lens by
applying said composition to said eye during wearing of said
contact lens.
2. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, wherein the
component (A) is a cellulose-based polymer.
3. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 2, wherein the
cellulose-based polymer is one or more member(s) selected from the
group consisting of hydroxyethyl cellulose, hydroxypropylmethyl
cellulose, and salts thereof.
4. The method of using a composition as a wetting solution--eye
drops for contact lenses according to any one of claims 1 to 3,
wherein said composition comprises the component (A) in an amount
of 0.0001 to 25 (w/v) %.
5. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, wherein the
terpenoid is menthol.
6. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, wherein said
composition comprises the component (B) in an amount of 0.0001 to
0.1 (w/v) %.
7. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, wherein said
composition further comprises (C) a nonionic surfactant.
8. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 7, wherein the
component (C) is one or more member(s) selected from the group
consisting of polyoxyethylene sorbitan fatty acid esters,
polyoxyethylene hydrogenated castor oil and
polyoxyethylene-polyoxypropylene copolymer.
9. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 7 or 8, wherein the
component (C) is polysorbate 80.
10. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 7, wherein said
composition comprises the component (C) in an amount of 0.001 to 5
(w/v) %.
11. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, wherein the contact
lens is a soft contact lens.
12. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 11, wherein the soft
contact lens is essentially in soft contact lens Group IV.
13. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 11, wherein the soft
contact lens is a soft contact lens made of silicone-hydrogel.
14. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, wherein a viscosity
value of said composition at 20.degree. C. is 1.1 mPas or more.
15. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, wherein the interval
between the use as a contact lens wetting solution and the first
application to eyes after fitting the contact lens is within 5
hours.
16. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, which comprises
suppressing dry eye or desiccation of said eye.
17. The method of using a composition as a wetting solution--eye
drops for contact lenses according to claim 1, which comprises
alleviating strain in said eye.
18. A method of using a composition comprising: (A) 0.0001 to 25
(w/v) % of one or more member(s) selected from the group consisting
of a cellulose-based polymer, a vinyl-based polymer, polyethylene
glycol, and dextran; (B) 0.0001 to 0.1 (w/v) % of a terpenoid; and
(C) 0.001 to 5 (w/v) % of a nonionic surfactant selected from the
group consisting of polyoxyethylene sorbitan fatty acid esters,
polyoxyethylene hydrogenated castor oil, and
polyoxyethylene-polyoxypropylene copolymer as a wetting
solution--eye drops for contact lenses, said method comprising:
adding said composition directly to a contact lens dropwise in
order to wet said contact lens; and then fitting said contact lens
on an eye; and then wetting said contact lens by applying said
composition to said eye which is wearing said contact lens.
19. A method of handling a contact lens comprising the following
steps: (1) adding dropwise a composition comprising (A) one or more
member(s) selected from the group consisting of a cellulose-based
polymer, a vinyl-based polymer, polyethylene glycol, and dextran
and (B) a terpenoid, directly to a contact lens in order to wet the
contact lens before fitting the contact lens; (2) fitting the
wetted contact lens to an eye; and (3) wetting the fitted contact
lens by applying said composition to said eye during wearing of the
contact lens.
Description
CROSS REFERENCE
[0001] The present application is a 37 C.F.R. .sctn.1.53 (b)
divisional of, and claims priority to, U.S. application Ser. No.
12/678,063, filed Mar. 12, 2010. Application Ser. No. 12/678,063 is
the national phase under 35 U.S.C. .sctn.371 of International
Application No. PCT/JP2008/066416, filed on Sep. 11, 2008. Priority
is also claimed to Japanese Application No. 2007-239049 filed on
Sep. 14, 2007 and Japanese Application No. 2008-028985 filed on
Feb. 8, 2008. The entire contents of each of these applications is
hereby incorporated by reference.
TECHNICAL FIELD
[0002] The present invention relates to an ophthalmic composition
for alleviating the influence of contact lens on eyes, more
specifically to a wetting solution--eye drops for contact lenses,
which is excellent, for example, in stabilization of tear film,
particularly lipid layer, suppression of sensation of dryness and
prevention of decline in visual function during wearing contact
lens.
BACKGROUND ART
[0003] Recently, contact lens, particularly soft contact lens
(hereinafter also referred to as SCL) have become very widely used
for the purpose of vision correction or beauty. Wearing contact
lens, however, places a load on eye though it varies between
individuals.
[0004] The typical complaint from contact lens users is eye
dryness. A healthy tear film is a structure of thin layers with
about 7 .mu.m thickness, which is composed of three layers: mucin,
aqueous and lipid layers from the eyeball side and protects cornea
from drying, stimulation by external environment or the like. In
particular, the lipid layer in the nearest position to the external
environment prevents evaporation of tear fluid, however, due to the
cause such as thinning or destabilization of tear film, the lipid
layer is also prone to become thin, inhomogeneous, or unstable, and
evaporation of tear fluid is promoted, and thus dry eye symptom
including eye desiccation is occurred. And such destruction
(destabilization) of tear film causes spots wherein the lipid layer
is extremely thin or not existed. These spots observed on the
surface of tear film is called dry spots, and the time elapsed
until the appearance of dry spots can be used for calculating the
tear film breakup time (BUT), accordingly, the dry spots is thought
to be one of the important indexes for diagnostic criteria of eye
desiccation or dry eye (see Journal of the eye, 22 (3): 279-287,
2005). Thus, it is of great significance if the time until the
appearance of dry spots can be delayed or the increase in number
and area of dry spots under the same time between blinks can be
suppressed, because these lead to the suppression of dry eye
symptom including eye desiccation or eye strain.
[0005] It has also been known that even if a person has healthy
eyes without lenses, when he wears contact lenses the tear film
becomes inhomogeneous and he easily feels desiccation of the eyes,
thus he is susceptible to dry eye. In particular, while wearing
SCL, the tear film on the SCL has a tendency to become very thin
and thus there is a phenomenon observed in which the lipid layer
often becomes extremely thin on the SCL or the lipid layer is
sometimes partially or totally absent. As a result, evaporation of
tear fluid is increased, and evaporation of water from inside the
SCL and eventually from under the SCL is promoted, which may cause
eye dryness or corneal disorder (see Journal of the eye, 22 (3):
311-316, 2005).
[0006] Therefore, in order to ensure safety for the eyes of contact
lens users, it is necessary to stabilize the tear film on the
outside surface of the lens, particularly, lipid layer continuously
and effectively.
[0007] A method of applying artificial tears was conventionally
taken to treat eye dryness, however, the method of only using
artificial tears could not achieve stabilization of tear film, and
thus a sufficient effect could not be obtained. Therefore, a system
for stabilizing the tear film surrounding the contact lens was
proposed in which polyvinylpyrrolidone is adsorbed on the surface
of an ionic contact lens to increase water retention ability of the
surface of the lens, and eye drops to the eye wearing a contact
lens and a wetting solution used therefor were also proposed (JP
2001-247466 A). Furthermore, an ophthalmic liquid composition has
been proposed in which long-chain alkyl derivatives of
polysaccharides is used to promote and maintain the formation of
trilaminar structure of tear film (JP 2007-77053 A). However, the
systems and the compositions described in these documents have not
sufficiently exerted an effect of stabilizing tear film,
particularly lipid layer continuously and effectively.
[0008] Further, other problems associated with wearing contact lens
include decreased contrast sensitivity. Contrast sensitivity is one
of the criteria for evaluation of visual function, and it is a
measure of the ability of distinguishing a slight difference of
brightness. Decreased contrast sensitivity may lead, for example,
to an accident because it is difficult for a person to distinguish
the contrast between the road surface and obstacles while walking,
or to an inconvenience in sports (especially, ball game) because it
is difficult for a person to perceive the contrast between ball and
background. It has been known that the decrease of contrast
sensitivity is caused by an ophthalmic surgery such as
keratorefractive surgery with the excimer laser, and aging, as well
as wearing of contact lens. And there is a report that decrease of
contrast sensitivity due to wearing of contact lens is associated
with wearing of varifocal contact lens or soft contact lens for
long term or use of extended-wear soft contact lens. As a solution
to these problems, there is an attempt to change the contact lens
itself, however, it has not been known that contrast sensitivity
can be improved by an ophthalmic composition.
[0009] Meanwhile, ophthalmic solutions such as eye drops, eye
washes or contact lens wetting solution have basically different
purposes of use and they are handled independently in use. Thus,
contact lens users are required to keep, for example, contact lens
wetting solution and eye drops separately and use them
independently. These solutions, however, are often similar in
appearance because of the dosage and so on, despite of the
difference in the purpose of use (application), therefore, there
was a risk of misuse. For seller, there also was a risk of inducing
misuses by consumers due to false recognition at providing
information or mix-ups of products. Accordingly, there has been a
wide demand from not only users but also sales persons for the
development of products that can be used conveniently and safely
with no risks of misuse.
DISCLOSURE OF THE INVENTION
Problems to be Solved by the Invention
[0010] As aforementioned, ophthalmic solutions such as eye drops
and contact lens wetting solution have been handled independently.
Although individual performance of these formulations has been
studied, the suitability of the combination of eye drops and a
contact lens wetting solution has not been sufficiently
investigated. The present inventors have surprisingly found that
when a contact lens is fitted with a conventional contact lens
wetting solution, and then another eye drops is applied, the
effects of sufficiently stabilizing the tear film, reducing eye
strain and improving contrast sensitivity are not obtained, and
even uncomfortable sensation in using such as a sensation of
astringency or dryness may be produced.
[0011] Thus, an object of the present invention is to provide an
ophthalmic composition that can stabilize the tear film during
wearing contact lens and suppress eye dryness, and also resolve eye
strain and decreased contrast sensitivity, and furthermore imparts
a favorable sensation in using.
[0012] Another object of the present invention is to provide an
ophthalmic composition that is highly convenient with no risk of
misusage and is highly safe.
[0013] Still another object of the present invention is to provide
an ophthalmic composition that shows a high efficiency and safety
at any steps in the course from manufacturing, distribution to
sales.
Means to Solve the Problem
[0014] As a result of intensive studies for solving the problems
described above, the present inventors found that all the above
mentioned problems can be solved by using a wetting solution--eye
drops for contact lenses comprising (A) one or more compounds
selected from the group consisting of a cellulose-based polymer, a
vinyl-based polymer, polyethylene glycol and dextran; and (B) a
terpenoid.
[0015] Thus, the present invention provides:
[1] A wetting solution--eye drops for contact lenses comprising (A)
one or more member (s) selected from the group consisting of a
cellulose-based polymer, a vinyl-based polymer, polyethylene glycol
and dextran; and (B) a terpenoid. [2] The wetting solution--eye
drops for contact lenses as set forth in [1], wherein the component
(A) is a cellulose-based polymer. [3] The wetting solution--eye
drops for contact lenses as set forth in [2], wherein the
cellulose-based polymer is one or more member(s) selected from the
group consisting of hydroxyethyl cellulose, hydroxypropylmethyl
cellulose, and salts thereof. [4] The wetting solution--eye drops
for contact lenses as set forth in any one of [1] to [3], which
comprises the component (A) in an amount of 0.0001 to 25 (w/v) %.
[5] The wetting solution--eye drops for contact lenses as set forth
in any one of [1] to [4], wherein the terpenoid is menthol. [6] The
wetting solution--eye drops for contact lenses as set forth in
anyone of [1] to [5], which comprises the component (B) in an
amount of 0.0001 to 0.1 (w/v) %. [7] The wetting solution--eye
drops for contact lenses as set forth in any one of [1] to [6],
which further comprises a nonionic surfactant [C]. [8] The wetting
solution--eye drops for contact lenses as set forth in [7], wherein
the component (C) is one or more member (s) selected from the group
consisting of polyoxyethylene sorbitan fatty acid esters,
polyoxyethylene hydrogenated castor oil and
polyoxyethylene-polyoxypropylene copolymer. [9] The wetting
solution--eye drops for contact lenses as set forth in [7] or [8],
wherein the component (C) is polysorbate 80. [10] The wetting
solution--eye drops for contact lenses as set forth in any one of
[7] to [9], which comprises the component (C) in an amount of 0.001
to 5 (w/v) %. [11] The wetting solution--eye drops for contact
lenses as set forth in any one of [1] to [10], wherein the contact
lens is a soft contact lens. [12] The wetting solution--eye drops
for contact lenses as set forth in [11], wherein the soft contact
lens is essentially in soft contact lens Group IV. [13] The wetting
solution--eye drops for contact lenses as set forth in [11],
wherein the soft contact lens is a soft contact lens made of
silicone hydrogel. [14] The wetting solution--eye drops for contact
lenses as set forth in any one of [1] to [13] for suppressing eye
desiccation or dry eye. [15] The wetting solution--eye drops for
contact lenses as set forth in any one of [1] to [13] for reducing
eye strain or improving contrast sensitivity.
The Effect of the Invention
[0016] The wetting solution--eye drops for contact lenses of the
present invention can efficiently stabilize the tear film during
wearing contact lens, and can suppress eye dryness, eye strain, or
contrast sensitivity decrease effectively.
[0017] The wetting solution--eye drops for contact lenses of the
present invention also have an effect of reducing a stress on eyes
caused by contact lens wearing. It is thought that eye dryness or
eye strain during wearing contact lens is also related to the
stress to corneal cells, and thus an effect of improving eye
dryness or reducing eye strain by the wetting solution--eye drops
for contact lenses of the present invention is accompanied with an
effect of reducing the stress caused by wearing contact lens.
[0018] In addition, the wetting solution--eye drops for contact
lenses of the present invention imparts a favorable sensation in
using and it is not necessary to have a contact lens wetting
solution and eye drops separately any more, and thus the solution
is highly convenient and portable with no risk of misuse and it is
safe as well.
[0019] Further, the wetting solution--eye drops for contact lenses
of the present invention has an advantages including cost reduction
in manufacturing stage, efficiency of transportation and display in
distribution stage, such as reduction of transportation cost, and
increase of safety in handling products in sales stage.
Accordingly, the wetting solution--eye drops for contact lenses of
the present invention can also contribute to the reduction of
energy consumption, and is thus useful for energy saving, which
means it can reduce the damage to the environment.
[0020] As described above, the present invention provides a wetting
solution--eyedrops, which exerts advantageous effects on achieving
suppression of eye dryness, reduction of eye strain and improvement
of contrast sensitivity during wearing contact lens, and is safe
and convenient, and which can make it possible to secure safety and
improve efficiency in the course from manufacturing to sales.
Therefore the present invention can simultaneously achieve
improvements of convenience and safety for the contact lens users,
and efficiencies in each stage from manufacturing, transportation
to sales.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 is a graph which shows an improvement effect on the
decreased contrast sensitivity during wearing contact lens by the
wetting solution--eye drops for contact lenses of the present
invention.
BEST MODES FOR CARRYING OUT THE INVENTION
[0022] The present invention is described in more detail below.
[0023] The following are definitions of terms used in this
description, claims and drawing.
[0024] The term "fitting" as used herein represents action (or
movement) of "putting a contact lens on an eye" and the term
"wearing" as used herein represents the condition in which contact
lens "exists on the cornea".
[0025] The term "%" as used herein represents w/v %, that is, the
weight (g) of each component (solute) dissolved in 100 mL of
solution unless otherwise indicated.
[0026] As used herein, the term "wetting solution--eye drops for
contact lenses" represents ophthalmic composition which
simultaneously has both functions as a contact lens wetting
solution and as eye drops applicable during wearing contact lens.
Further, the wetting solution--eye drops of the present invention
is an ophthalmic composition wherein the same formulation can be
used as a wetting solution when contact lens is fitted, and then
can be used as eye drops to an eye with a contact lens. Throughout
the specification, the term "wetting solution--eye drops for
contact lenses" may be referred to only as "wetting solution--eye
drops".
[0027] Further, the term "contact lens" as used herein is intended
to encompass any types of contact lenses such as hard, oxygen
permeable hard and soft contact lens, unless otherwise
indicated.
[0028] Also the term "categories of soft contact lenses" as used
herein represents SCL category based on the document titled
"Regarding a Method of Classification of Soft Contact Lens" which
is stipulated in the notification No. 645, "How to Deal with a Data
to be Attached for Application for Manufacturing (Import) Approval
of Soft Contact Lens and Disinfectant for Soft Contact Lens",
Evaluation and Licensing Division, Pharmaceutical and Medical
Safety Bureau--Ministry of Health, Labor and Welfare (former
Ministry of Health and Welfare), Mar. 31, 1999. Among the
categories, the SCL belonging to Group IV has a common property in
which water content ratio is 50% or more and the ratio of mole % of
monomers containing negative ion to constituent monomers of
starting polymer in total is 1% or more. This classification
follows the classification of soft contact lens established by FDA
(U.S. Food and Drug Administration).
[0029] The term "essentially" is intended to include any soft
contact lens which can be understood by one skilled in the art as
being equal to those belonging to said category in the material,
function and so on.
[0030] The contact lens made of silicone hydrogel material refers
to a contact lens produced by using a material in which
silicone-containing material (for example, TRIS which is a polymer
of silicone with acrylate, or TRIS derivative) is copolimerized
with hydrophilic monomer (for example, hydroxyethyl methacrylate,
dimethylacrylamide), and the names of the materials according to
USAN (United State Adopted Name) include, for example,
LotrafilconA, LotrafilconB, BalafilconA, GalyfilconA,
SenofilconA.
[0031] The wetting solution--eye drops for contact lenses according
to the present invention is characterized by comprising (A) one or
more compounds selected from the group consisting of a
cellulose-based polymer, a vinyl-based polymer, polyethylene glycol
and dextran; and (B) a terpenoid. The inclusion of these components
can stabilize the tear film during wearing contact lens, thus can
suppress eye dryness, therefore is effective for the reduction of
eye strain and the improvement of contrast sensitivity and
simultaneously enhance sensation of using. Also, when the same
formulation of the present invention is used as a contact lens
wetting solution and/or as eye drops, medicinal solutions with
different properties do not have to be mixed on cornea and
conjunctiva via contact lens. Although this mechanism has not been
elucidated in detail yet, it is thought that the influence of the
interaction between the medicinal solution and the contact lens on
eyes or tear fluid might be minimized, and therefore the tear film
can be kept to be stable, or eye strain can be reduced, contrast
sensitivity can be improved, or the sensation of using can be
enhanced as described above.
[0032] The wetting solution--eye drops for contact lenses of the
present invention comprises one or more compounds selected from the
group consisting of a cellulose-based polymer, a vinyl-based
polymer, polyethylene glycol and dextran (hereinafter may be simply
referred to as component (A)).
[0033] The cellulose-based polymer that can be used includes a
cellulose-based polymer compound that can be obtained by
substituting a hydroxyl group of the cellulose with other
functional group and can give a viscosity to aqueous composition,
and thus can be applicable to a contact lens. A functional group
that may substitute the hydroxyl group of the cellulose includes
methoxy group, ethoxy group, hydroxymethoxy group, hydroxyethoxy
group, hydroxypropoxy group, carboxymethoxy group, carboxyethoxy
group and the like. Typical examples of the cellulose-based polymer
include methylcellulose, ethylcellulose, hydroxyethyl cellulose,
hydroxymethyl cellulose, hydroxypropyl cellulose,
hydroxypropylmethyl cellulose, carboxymethyl cellulose,
carboxyethyl cellulose and salts thereof. Such salts are preferably
pharmacologically acceptable salts, among which alkali metal salts
are more preferred, and the salt such as sodium salt or potassium
salt is particularly preferred. Although there is no limitation on
the substitution degree of substituents or the molecular weight of
the cellulose-based polymer used in the present invention, said
polymer may have a weight-average molecular weight of, for example,
about 5000 to 1,000,000, preferably about 10,000 to 500,000 and
more preferably about 10,000 to 100,000. These cellulose-based
polymers are commercially available, and may be used alone or in
any combination of two or more types thereof. From the viewpoint of
further enhancing the effect of the invention, the cellulose-based
polymers are one or more compounds preferably selected from the
group consisting of methylcellulose, hydroxyethyl cellulose,
hydroxypropylmethyl cellulose, hydroxypropyl cellulose,
carboxymethyl cellulose and salts thereof. More preferred examples
include hydroxypropylmethyl cellulose, hydroxyethyl cellulose and
carboxymethylcellulose sodium, and particularly preferred examples
are hydroxypropylmethyl cellulose or hydroxyethyl cellulose.
[0034] The content of the cellulose-based polymer in the wetting
solution--eye drops for contact lenses of the present invention, is
not limited because the content also varies depending on the kind
of the compound or the molecular weight thereof, but is usually
0.0001 to 25%, preferably 0.001 to 10%, more preferably 0.001 to
7%, even more preferably 0.005 to 5%, particularly preferably 0.01
to 1% as a ratio of the total amount of these compounds to the
total amount of the wetting solution--eye drops for contact
lenses.
[0035] The vinyl-based polymer that can be used includes a polymer
that can give a viscosity to aqueous composition, and thus can be
applicable to a contact lens. Typical examples of the vinyl-based
polymer include vinyl alcohol polymer such as polyvinyl alcohol
(completely or partially saponified), vinyl pyrrolidone polymer
such as polyvinylpyrrolidone, and carboxy vinyl polymer and so on.
Although there is no limitation in the molecular weight of the
vinyl-based polymer used herein, the vinyl-based polymer may have a
weight-average molecular weight of, for example, about 5,000 to
1,000,000, preferably about 10,000 to 500,000 and even more
preferably about 10,000 to 400,000. These vinyl-based polymers are
commercially available, and may be used alone or in any combination
of two or more types thereof. From the viewpoint of further
enhancing the effect of the invention, polyvinylpyrrolidone K25,
polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, polyvinyl
alcohol (partially saponified) and carboxy vinyl polymer are
preferred, polyvinyl alcohol (partially saponified) and carboxy
vinyl polymer are more preferred, and polyvinyl alcohol (partially
saponified) is particularly preferred.
[0036] The content of the vinyl-based polymer in the wetting
solution--eye drops for contact lenses of the present invention is
not limited because the content also varies depending on the kind
of the compound or the molecular weight thereof, but is usually
0.001 to 25%, preferably 0.001 to 10%, more preferably 0.005 to 5%,
even more preferably 0.01 to 5%, particularly preferably 0.1 to 3%
as a ratio of the total amounts of these compounds to the total
amounts of the wetting solution--eye drops for contact lenses.
[0037] Dextran is a water-soluble polymer compound that can be
obtained by partially hydrolyzing a polysaccharide that is produced
from sucrose as a starting material by certain lactic acid
bacteria. The dextran that can be used in the present invention may
have a weight-average molecular weight of about 5,000 to 1,000,000,
preferably about 10,000 to 500,000 and more preferably about 10,000
to 100,000. These dextrans are commercially available, and may be
used alone or in any combination of two or more types thereof. From
the viewpoint of further enhancing the effect of the invention,
dextran, dextran 70 and dextran 40 are preferred, and dextran 70 is
particularly preferred.
[0038] The content of the dextran in the wetting solution--eye
drops for contact lenses of the present invention is usually 0.001
to 25%, preferably 0.001 to 10%, more preferably 0.01 to 10%, even
more preferably 0.01 to 5%, particularly preferably 0.01 to 1%,
further particularly preferably 0.01 to 0.1% as a ratio of the
total amount of these dextrans to the total amount of the wetting
solution--eye drops for contact lenses.
[0039] Polyethyleneglycol that may be used in the present invention
is also referred to as macrogol. Although there is no limitation on
the substitution degree of substituents or the molecular weight of
the polyethylene glycol, the weight-average molecular weight of the
polyethylene glycol may be about 100 to 50,000, preferably about
400 to 20,000 and more preferably about 2000 to 10,000. Also, these
polyethylene glycols are commercially available and may be used
alone or in any combination of two or more types thereof. Among
them, from the viewpoint of further enhancing the effect of the
invention, macrogol 6000, macrogol 4000 and macrogol 400 are
preferred, and macrogol 6000 and macrogol 4000 are particularly
preferred.
[0040] The content of polyethylene glycol in the wetting
solution--eye drops for contact lenses of the present invention is
usually 0.001 to 25%, preferably 0.001 to 10%, more preferably 0.01
to 10%, even more preferably 0.05 to 5%, particularly preferably
0.05 to 2% as a ratio of the total amount of these polyethylene
glycols to the total amount of the wetting solution--eye drops for
contact lenses.
[0041] The component (A) of the present invention can be used alone
or in any combination of two or more types thereof. From the
viewpoint of further enhancing the effect of the invention, the
component (A) is preferably a cellulose-based polymer, among which,
hydroxypropyl methylcellulose and hydroxyethyl cellulose are
particularly preferable.
[0042] The content of the component (A) in the wetting
solution--eye drops for contact lenses of the present invention is
usually 0.0001 to 25%, preferably 0.001 to 10%, more preferably
0.005 to 10%, further preferably 0.01 to 7%, particularly
preferably 0.01 to 5% as a ratio of the total amount of these (A)
components to the total amount of the wetting solution--eye drops
for contact lenses.
[0043] The wetting solution--eye drops for contact lenses of the
present invention further comprises a terpenoid (hereinafter may be
simply referred to as component (B)).
[0044] The terpenoid used in the wetting solution--eye drops for
contact lenses of the present invention includes menthol
(l-menthol, dl-menthol, etc.), menthone, camphor (d-camphor,
dl-camphor, etc.), borneol (d-borneol, dl-borneol, etc.), geraniol,
cineol, citrale, linalool, anethole, limonene, eugenol and the
like. These compound may be either d-form, l-form or dl-form,
however, from the viewpoint of further enhancing the effect of the
invention, it is preferable to use l-menthol, d-camphor,
dl-camphor, d-borneol, dl-borneol or geraniol. Among them,
l-menthol, d-camphor, dl-camphor and geraniol are preferred, with
l-menthol being further preferred.
[0045] Also the above-mentioned terpenoid may also be contained in
an essential oil, and a preferred essential oil includes mentha
oil, peppermint oil, eucalyptus oil, bergamot oil, fennel oil,
cinnamon oil, rose oil and the like. These terpenoid can be used
alone or in any combination of two or more kinds thereof.
[0046] It is preferred that the content of the terpenoid in the
wetting solution--eye drops for contact lenses of the present
invention is, from the viewpoint of further enhancing the effect of
the invention, usually 0.0001 to 0.1% as a ratio of the total
amount of the terpenoid to the total amount of the wetting
solution--eye drops for contact lenses. It is more preferably
0.0001 to 0.07%, even more preferably 0.0005 to 0.05%, and
particularly preferably 0.0005 to 0.01%.
[0047] When a terpenoid-containing essential oil is used as the
component (B), the blending ratio of the essential oil is decided
such that the content of terpenoid in the essential oil to be
blended can meet the ratio as described above.
[0048] In addition, the wetting solution--eye drops for contact
lenses of the present invention may comprise an appropriate
nonionic surfactant (hereinafter may be simply referred to as
component (C)), if desired.
[0049] The nonionic surfactant used in the present invention can
include the surfactants which can be applied to an ophthalmic
composition for contact lens by those skilled in the art, for
example, polyoxyethylene-polyoxypropylene block copolymer
(hereinafter also referred to as polyoxyethylenepolyoxypropylene
copolymer) such as poloxamer 407, poloxamer 235 and poloxamer 188;
POE-POP block copolymer adduct of ethylene diamine such as
poloxamine; POE sorbitan fatty acid esters such as monolaurate POE
(20) sorbitan (polysorbate 20), POE (20) sorbitan monoleate
(polysorbate 80), POE sorbitan monostearate (polysorbate 60), POE
sorbitan tristearate (polysorbate 65); POE hydrogenated castor oils
such as POE hydrogenated castor oil 5, POE hydrogenated castor oil
10, POE hydrogenated castor oil 20, POE hydrogenated castor oil 40,
POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE
hydrogenated castor oil 100; POE alkyl ethers such as POE (9)
lauryl ether; POE.cndot.POP alkyl ethers such as POE (20) POP (4)
cetyl ether; POE alkyl phenyl ethers such as POE (10) nonylphenyl
ether. Here, POE represents polyoxyethylene, POP represents
polyoxypropylene and the figures shown in the parentheses represent
the number of added moles.
[0050] Among them, polyoxyethylene-polyoxypropylene block
copolymer, POE sorbitan fatty acid esters and POE hydrogenated
castor oils are preferable, and poloxamer 407, polysorbate 80 and
POE hydrogenated castor oil 60 are particularly preferable.
[0051] The content of the nonionic surfactant in the wetting
solution--eye drops for contact lenses of the present invention
cannot be uniformly defined since the content varies depending on
the kind of the surfactant and the like, but is usually 0.001 to
5%, preferably 0.001 to 1.5%, more preferably 0.001 to 1%, even
more preferably 0.005 to 0.5%, particularly preferably 0.05 to 0.3%
as a ratio of the total amount of these surfactants to the total
amount of the wetting solution--eye drops for contact lenses.
[0052] Preferably, the wetting solution--eye drops for contact
lenses of the present invention comprises appropriate buffering
agents, if desired. The buffering agents used in the present
invention include borate buffering agent, phosphate buffering
agent, carbonate buffering agent, citrate buffering agent, acetate
buffering agent, HEPES buffering agent, MOPS buffering agent and
the like. More specific examples of the buffering agents include a
compound selected from the group consisting of boric acid, sodium
borate, potassium tetraborate, borax, potassium metaborate,
phosphoric acid, disodium hydrogen phosphate, sodium dihydrogen
phosphate, potassium dihydrogen phosphate, carbonic acid, sodium
bicarbonate, sodium carbonate, citric acid, sodium citrate,
potassium citrate, acetic acid, sodium acetate, HEPES, MOPS, and
hydrates thereof, and a combination of two or more compounds
selected from the above agents.
[0053] Preferred examples of the buffering agents include borate
buffering agent, phosphate buffering agent, carbonate buffering
agent and citrate buffering agent. Particularly preferred buffering
agents are borate buffering agent or phosphate buffering agent.
More specifically, particularly preferred buffering agents include
borate buffering agents, for example, boric acid, borate such as
alkaline metal borate and alkaline earth metal borate, and a
combination of boric acid and borate, with boric acid or borax
being particularly preferred, and phosphate buffering agents, for
example, phosphoric acid, phosphate such as alkaline metal
phosphate or alkaline earth metal phosphate, hydrates thereof, and
a combination of phosphoric acid and phosphate, with disodium
hydrogen phosphate, sodium dihydrogen phosphate and hydrates
thereof being particularly preferred.
[0054] The content of the buffering agent in the wetting
solution--eye drops for contact lenses of the present invention
cannot be uniformly defined, since the content varies depending on
the kind of the buffering agent and the like, but is usually 0.001
to 5%, preferably 0.001 to 3%, more preferably 0.005 to 2.0%, even
more preferably 0.005 to 1.5%, particularly preferably 0.05 to 1.5%
as a ratio of the total amount of these buffering agents to total
amounts of the wetting solution--eye drops for contact lenses.
[0055] Preferably, the wetting solution--eye drops for contact
lenses of the present invention comprises an appropriate inorganic
salt, if desired. The inorganic salts include potassium chloride,
sodium chloride, sodium bicarbonate and sodium carbonate, and may
be used alone or in any combination of two or more types
thereof.
[0056] The content of inorganic salt in the wetting solution--eye
drops for contact lenses of the present invention cannot be
uniformly defined since the content varies depending on the kind of
the inorganic salt and the like, but is usually 0.001 to 5%,
preferably 0.01 to 1.5%, more preferably 0.1 to 0.7% as a ratio of
the total amount of these inorganic salts to the total amount of
the wetting solution--eye drops for contact lenses.
[0057] Preferably, the wetting solution--eye drops for contact
lenses of the present invention comprises an appropriate
ethylenediamine acetic acid derivative or a salt thereof, if
desired. Typical examples of the ethylenediamine acetic acid
derivative or salts thereof include edetic acid
(ethylenediaminetetraacetic acid, EDTA), ethylenediaminediacetic
acid (EDDA), diethylenetriaminepentaacetic acid (DTPA),
N-(2-hydroxyethyl)ethylenediaminetriaceticacid (HEDTA) or salts
thereof. The salt of ethylenediamine acetic acid derivative
includes a pharmacologically or physiologically acceptable salt,
for example, a salt with alkaline metal (sodium, potassium or the
like) or a salt with alkaline-earth metal (calcium, or the like).
Among them, ethylenediaminetetraacetic acid or a salt thereof, such
as ethylenediaminetetraacetate calcium disodium,
ethylenediaminetetraacetate disodium or ethylenediaminetetraacetate
disodium.cndot.dihydrates (hereinafter also referred to as sodium
edetate) are preferred, and ethylenediaminetetraacetate
disodium.cndot.dihydrates is particularly preferred. These can be
used alone or in any combination of two or more thereof.
[0058] The content of ethylenediamine acetic acid derivative or a
salt thereof in the wetting solution--eye drops for contact lenses
of the present invention cannot be uniformly defined since the
content varies depending on the molecular weight, the kind thereof
or the like, but is preferably 0.0001 to 1%, more preferably 0.0005
to 0.5%, even more preferably 0.001 to 0.3%, particularly
preferably 0.001 to 0.05% as a ratio of the total amount of these
ethylenediamine acetic acid derivatives or salts thereof to the
total amount of the wetting solution--eye drops for contact
lenses.
[0059] Also from the viewpoint of further enhancing the effect of
the invention, it is more preferred that the wetting solution--eye
drops for contact lenses of the present invention comprises an
derivative of ethylenediamineacetic acid or a salt thereof, a
nonionic surfactant, an inorganic salt and a buffering agent in
combination.
[0060] The content of ethylenediamine acetic acid derivative or a
salt thereof, nonionic surfactant, inorganic salt or buffering
agent in the wetting solution--eye drops for contact lenses of the
present invention is preferably 0.01 to 5%, particularly preferably
0.05 to 3%, as a ratio of the total amount of these components to
the total amount of the wetting solution--eye drops for contact
lenses.
[0061] Preferably, the wetting solution--eye drops for contact
lenses of the present invention is used particularly for soft
contact lens in a group of contact lens. This is because soft
contact lens is prone to cause a feeling of dryness and thus puts a
strain on eyes. And also because it is useful for soft contact lens
with high moisture content, which is specifically prone to cause a
feeling of dryness, particularly for soft contact lens of SCL Group
IV. In addition, unexpectedly, the wetting solution--eye drops for
contact lenses of the present invention shows remarkable
advantageous effect on the soft contact lens made of
silicone-hydrogel, and is thus preferably used for said soft
contact lens.
[0062] The wetting solution--eye drops for contact lenses of the
present invention is appropriate for comprising various components
(including pharmacologically-active component or
physiologically-active component) in combination with each
other.
[0063] Decongestants, drugs for modulating ocular muscles,
anti-inflammatory drugs or astringents, antihistamine drugs or
antiallergic drugs, vitamins, amino acids or local anesthetics
usually used for ophthalmic composition or the like can be
exemplified. Specifically, the following components can be
exemplified.
[0064] Decongestants: for example, .alpha.-adrenergic drugs such as
epinephrine, epinephrine hydrochloride, ephedrine hydrochloride,
oxymetazoline hydrochloride, tetrahydrozoline hydrochloride,
naphazoline hydrochloride, phenylephrine hydrochloride,
methylephedrine hydrochloride, epinephrine bitartrate, naphazoline
nitrate or the like, all of which may be any form of d-form, l-form
or dl-form;
[0065] Drugs for modulating ocular muscles: for example,
cholinesterase inhibitor with active centers similar to that of
acetylcholine, such as neostigmine methylsulfate, tropicamide,
helenien atropine sulfate or the like;
[0066] Anti-inflammatory drugs or astringents: for example, zinc
sulfate, zinc lactate, allantoin, .epsilon.-aminocaproic acid,
indomethacin, lysozyme chloride, silver nitrate, pranoprofen,
sodium azulene sulfonate, dipotassiumglycyrrhizinate, diclofenac
sodium, bromfenac sodium, berberine chloride, berberine sulfate or
the like;
[0067] Antihistamine drugs or Antiallergic drugs: for example,
acitazanolast, amlexanox, ibudilast, tranilast, diphenhydramine
hydrochloride, levocabastine hydrochloride, ketotifen fumarate,
sodium cromoglycate, pemirolast potassium, chlorpheniramine maleate
or the like;
[0068] Vitamins: for example, retinol acetate, retinol palmitate,
pyridoxine hydrochloride, sodium flavin adenine dinucleotide,
pyridoxal phosphate, cyanocobalamin, panthenol, calcium
pantothenate, sodium pantothenate, ascorbic acid, tocopherol
acetate or the like;
[0069] Amino acids: for example, potassium aspartate, sodium
aspartate, magnesium and potassium aspartate, glutamic acid, sodium
glutamate, aminoethylsulfonic acid or the like;
[0070] Acid mucopolysaccharides: for example, sodium chondroitin
sulfate or the like;
[0071] Local anesthetics: for example, chlorobutanol, oxybuprocaine
hydrochloride, cocaine hydrochloride, cornecaine hydrochloride,
dibucaine hydrochloride, tetracaine hydrochloride,
diethylaminoethyl p-butylaminobenzoate hydrochloride, piperocaine
hydrochloride, procaine hydrochloride, proparacaine hydrochloride,
hexothiocaine hydrochloride, lidocaine hydrochloride or the
like;
[0072] Also various component or additives can be selected
appropriately within the range of not being adversely affected,
depending on use or form, according to a conventional method and
then one or more kind of thereof may be contained in the wetting
solution--eye drops for contact lenses of the present invention.
These components or additives includes for example, carrier that be
usually used for preparation of semi-solid formulation or liquid
formulation (for example, water, aqueous solvent or aqueous or oily
base or the like), or a variety of additives such as thickener,
saccharides, sugar alcohols, acid mucopolysaccharides, surfactant,
preservatives, disinfectants or antibacterial drugs, pH adjusters,
tonicity agents and stabilizers or the like.
[0073] The representative examples of component that used in the
wetting solution--eye drops for contact lenses of the present
invention are the following ones, but not limited thereto; i.e.
[0074] Saccharides: for example, glucose, cyclodextrin;
[0075] Sugar alcohols: for example, xylitol, sorbitol,
mannitol;
[0076] Acid mucopolysaccharides: alginic acid, sodium alginate;
[0077] Surfactant: for example, surfactants other than the nonionic
surfactant as aforementioned, for example, glycin type-ampholytic
surfactant such as alkyldiaminoethylglycine; alkyl
tetraalkylammonium salts (for example, cationic surfactant such as
benzalkonium chloride, benzethonium chloride);
[0078] Preservatives, Disinfectants or Antibacterial drugs: for
example, alkyldiaminoethylglycine hydrochloride, sodium benzoate,
ethanol, benzalkonium chloride, benzethonium chloride,
chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium
sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl
parahydroxybenzoate, propyl parahydroxybenzoate, butyl
parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol,
benzyl alcohol, biguanide (for example, polyhexamethylene biguanide
or hydrochloride salt thereof), polidronium chloride, Glokill.RTM.
(Rhodia) or the like;
[0079] pH adjusters: for example, hydrochloric acid, boric acid,
epsilon-aminocaproic acid, acetic acid, sodium hydroxide, sodium
bicarbonate, sodium carbonate, borax, triethanolamine,
monoethanolamine or the like;
[0080] Tonicity agents: for example, sodium hydrogen sulfite,
sodium sulfite, magnesium chloride, potassium acetate, sodium
acetate, sodium thiosulfate, magnesium sulfate, glycerin, propylene
glycol or the like;
[0081] Stabilizers: for example, dibuthyl hydroxytoluene,
trometamol, sodium formaldehyde sulfoxylate (Rongalite),
tocopherol, sodium pyrosulfite, monoethanolamine, aluminum
monostearate or the like.
[0082] The viscosity of the wetting solution--eye drops for contact
lenses of the present invention can be initially adjusted at an
appropriate level in order to obtain a desired effect and the level
can be maintained stably for extended period. When the viscosity of
the ophthalmic composition for contact lens is set, the viscosity
value at 20.degree. C. is preferably designed to maintain 1.1 mPas
or more, and can be designed to be usually 1.1 to 300 mPas,
preferably 1.3 to 100 mPas, particularly preferably 1.5 to 80
mPas.
[0083] Viscosity can be measured according to a method with the
rotational viscometer of cone-plate type (a method described in 45.
Viscosity Determination, Method II Viscosity measurement by
rotational viscometer, "(3) Cone-flat plate-type rotational
viscometer" in General Tests, The Japanese Pharmacopoeia Fourteenth
Edition), specifically, it can be measured by a commercially
available rotational viscometer of cone-plate type and an
appropriately selected rotor. For example, the viscosity at
20.degree. C. can be measured by using commercially available
viscometer of type E (manufactured by TOKIMEC Inc. and supplied by
TOKI SANGYO, Co., Ltd., Japan) and an appropriately selected rotor,
and by calibrating with petroleum-derived hydrocarbon oil
(Newtonian fluid) that is defined by JIS (Japanese Industrial
Standards) 28809 as a calibrating standard for each determination
of the test samples. Specifically, the viscosity is measured
according to the viscosity determination described in JP
2006-348055 A (the condition of measurement is described
below).
[0084] The wetting solution--eye drops for contact lenses of the
present invention is adjusted to have an osmolality within the
biologically acceptable range, if desired. The osmolality is
usually 0.3 to 4.1, preferably 0.4 to 4.1, more preferably 0.3 to
2.1, particularly preferably 0.5 to 1.4 as an osmolality ratio to
that of physiological saline. The osmolality ratio is measured by
referring to the method described in Osmolality Determination, in
General Tests, The Japanese Pharmacopoeia Fifteenth Edition.
[0085] The pH of the wetting solution--eye drops for contact lenses
of the present invention is adjusted to a value within the range to
make the solution of the present invention applicable to human
body, if desired. The pH is usually 4.0 to 9.0, preferably 5.0 to
8.5, particularly preferably 5.5 to 8.5. The pH can be adjusted
with a buffering agent or a pH adjuster as described above.
[0086] The wetting solution--eye drops for contact lenses of the
present invention can be prepared by a known method in the art, and
a step of filtration sterilization, a step of filling the solution
in a container, or the like may be included, if desired.
[0087] The method of using the wetting solution--eye drops for
contact lenses of the present invention includes for example, a
method of [the use at the time of fitting a contact lens (just
before fitting) by dropwise adding the wetting solution--eye drops
for contact lenses directly to a contact lens, wetting both sides
or one side of the contact lens with an appropriate amount thereof
(for example, suitably, one or two drop(s) for one time), and then
fitting said contact lens] (the use explained in the parenthesis
may be also described as "usage as a contact lens wetting
solution"). Also included a method of [the use during wearing a
contact lens by applying an appropriate amount (for example,
suitably, one or two drop(s) for one time) of the wetting
solution--eye drops for contact lenses to eyes (the use explained
in the parenthesis may also be described as "usage as eye drops").
The number of instillation into eyes for a day is not limited, but
is normally in a range of 1 to 10 times, preferably from 1 to 6
times, particularly preferably from 5 to 6 times.
[0088] The particularly recommended usage of the wetting
solution--eye drops for contact lenses is the usage wherein the
interval between the use as a contact lens wetting solution as
described above and the first application to eyes after fitting the
contact lens is within 5 hours, preferably 2 hours, more preferably
1 hour, even more preferably 30 minutes, particularly preferably 10
minutes, further particularly preferably 2 minutes. The application
thereafter is carried out similarly to the usual usage of eye
drops.
[0089] The present invention may further comprises the following
steps of handling contact lens: (1) a step of adding dropwise the
wetting solution--eye drops for contact lenses directly to a
contact lens in order to wet both sides or one side of the contact
lens with an appropriate amount thereof (for example, suitably, one
or two drop(s) for one time) when fitting a contact lens (just
before fitting); (2) a step of fitting a contact lens to an eye;
(3) a step of wetting a contact lens by applying said solution to
an eye during wearing the contact lens. Also, the present invention
may comprise the following steps of handling contact lens: (4) a
step of applying said solution to an eye to wet a contact lens when
removing the contact lens (just before removing); (5) a step of
removing a contact lens from an eye; (6) a step of applying the
wetting solution--eye drops for contact lenses to an eye just
before fitting a contact lens). For handling contact lens, an
appropriate step may be selected from the above steps, if
desired.
[0090] In the meanwhile, from the viewpoint of further enhancing
the effect of the invention, it is the target of the invention to
subject the wetting solution--eye drops for contact lenses
preferably to the both usage as a contact lens wetting solution and
usage as eye drops while wearing contact lens, however the solution
of the invention can also be for either use only.
EXAMPLES
[0091] The present invention is illustrated in more detail by Test
Examples and Examples, but should not be construed to be limited
thereto.
[0092] In Test Examples, the tests were conducted as successively
as possible to keep the measuring condition, in particular the
subject's condition almost constant. Each Test Example was carried
out independently.
[0093] The viscosities in each Example and Comparative Example were
determined by using TVE-20L cone-plate type viscometer
(manufactured by TOKIMEC Inc. and supplied by TOKI SANGYO, Co.,
Ltd., Japan), which is a kind of E-type viscometer, under the
following measuring condition according to the manufacturer's
instructions. Unless stated otherwise, the measurement was carried
out according to the viscometric determination described in JP A
2006-348055. The measuring condition used was as follows.
Measuring Condition:
[0094] Rotational frequency: 100 rpm (the viscosity is measured at
the highest rotational frequency among the measurable rotation
frequencies depending on each formulation since the acceptable
range of rotational frequency is different depending on the
viscosity.)
[0095] Amount of sample: 1 mL
[0096] Temperature: 20.degree. C.
[0097] Time: The viscosity after 3 minutes was defined as the
measurement.
Test 1: Evaluation with Dry Eye Observation Instrument (DR-1, Kowa
Company, Ltd.)
(Test Method)
[0098] Each wetting solution--eye drops for contact lenses of
Examples 1 to 6 and Comparative Examples 1 to 3 was prepared by the
formulation of Table 1 according to a usual preparative method
(conventional method) of eye drops and others, and was filled into
a polyethylene terephthalate container (volume: 10 mL) and plugged
with a nozzle and a cap. Soft contact lens (trade name: Ciba Vision
K.K., soft contact lens Group I (silicone-hydrogel lens, main
material: LotrafilconA) (hereinafter also referred to as "SCL1")
and a soft contact lens (trade name: Johnson & Johnson K.K.,
soft contact lens Group IV (main material: EtafilconA) (hereinafter
also referred to as "SCL2") were used. After wetting both sides of
these contact lenses with one drop of the wetting solution--eye
drops of each formulation, the contact lenses were fitted, and at
two minutes after the fitting, the wetting solution--eye drops of
the same formulation was applied to eyes.
[0099] Thereafter, an evaluation was carried out according to the
condition of each test (1) to (3). Three subjects were selected
from persons who usually wore contact lenses and had a sensation of
dryness (persons who are prone to dry eye). After a subject was
examined with a kind of testing solution, he rested his eyes
sufficiently, and then he was examined with the next testing
solution.
(1) Evaluation of the Area of Dry Spot--1
[0100] The wetting solution--eye drops for contact lenses was
subjected to the usage as a contact lens wetting solution under the
condition as described above, and then, the solution was applied to
eyes while wearing contact lenses, followed by the evaluation of
the number of dry spot under the following condition.
[0101] The dry spot was observed on a dry eye observation
instrument (DR-1, Kowa Company, Ltd.) which was used for
observation of an interference color of the tear fluid lipid layer.
Specifically, the number and the size of dry spots on the eye
surface was measured at one second after the beginning of a
blinking observed at about two minutes after the application to
eyes.
[0102] Analysis A:
[0103] The dry spots observed for each wetting solution--eye drops
for contact lenses of Example 1 and Comparative Examples 1 and 2
were divided into three kinds of the size according to Table 2, and
then the number of the spots of each size was counted. The score
for each size in Table 2 was multiplied by the number of the spots.
At last, subtotal of the score for each size was summed to obtain
"the total score of dry spot" for each formulation. The average
"total score of dry spot" for three subjects was evaluated
according to Table 3 and the result was shown in Table 4.
[0104] Analysis B:
[0105] For each dry spot observed for each wetting solution--eye
drops for contact lenses of Examples 1 to 6 and Comparative
Examples 1 to 2, the area value was calculated from the image
obtained and then a sum of the area value was calculated as a total
area for each formulation. Thereafter, the results of the three
subjects were averaged, and each relative value of the total area
for each formulation of Examples and Comparative Examples was
calculated by defining the total area of Example 1 as the value of
1, and the result was shown in Table 5 as "relative evaluation of
the total area of dry spot".
TABLE-US-00001 TABLE 1 Ex. Comp. Comp. Comp. Ex. Ex. Ex. Ex. Ex. 1
1 2 3 2 3 4 5 6 HPMC .sup.1) 0.2 0.2 -- -- 0.2 0.2 -- -- --
Polyvinyl -- -- -- -- -- -- 2.5 -- -- Pyrrolidone K90 Macrogol --
-- -- -- -- -- -- 1 -- 4000 Dextran -- -- -- -- -- -- -- -- 1 70
l-Menthol 0.005 -- 0.005 -- -- -- 0.002 -- -- d-Camphor -- -- -- --
0.015 -- -- 0.005 -- Geraniol -- -- -- -- -- 0.005 -- -- 0.003
Sodium 0.44 0.44 0.44 0.44 0.44 0.44 0.44 0.44 0.44 chloride
Potassium 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 chloride
Polysorbate 0.05 0.05 0.05 -- 0.05 0.05 0.05 0.05 0.05 80 Boric 1.0
1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 acid Borax 0.2 0.2 0.2 0.2 0.2 0.2
0.2 0.2 0.2 Edetate 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05
sodium Purified q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. water
Total volume 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL 100
mL 100 mL pH 7.3 7.3 7.3 7.3 7.3 7.3 7.3 7.3 7.3 Osmolality 1.2 1.2
1.2 1.2 1.2 1.2 1.2 1.2 1.2 ratio .sup.1) Hydroxypropyl
methylcellulose 2906 (trade name: 65SH-4000 (Shin-Etsu Chemical.
Co., Ltd.)
TABLE-US-00002 TABLE 2 Criteria Score Diameter under 0.1 mm 1 point
Diameter 0.1 mm and more, under 0.2 mm 2 points Diameter 0.2 mm and
more 3 points
TABLE-US-00003 TABLE 3 Evaluation of total Total score of dry spot
score of dry spot 41 points and more not good 31 points to 40
points moderate 21 points to 30 points good 20 points and less very
good
TABLE-US-00004 TABLE 4 Evaluation of total score of dry spot Soft
contact lens Ex. 1 Comp. 1 Comp. 2 SCL1 very good moderate moderate
SCL2 very good moderate moderate
TABLE-US-00005 TABLE 5 Evaluation of total score of dry spot Soft
contact Ex. Comp. Comp. Ex. Ex. Ex. Ex. Ex. lens 1 1 2 2 3 4 5 6
SCL1 1.0 4.1 3.2 0.6 0.9 1.0 1.8 1.9 SCL2 1.0 12.0 7.7 2.5 4.4 3.0
5.0 3.7
[0106] Dry spot is recognized as an index representing dry eye or
desiccation of eye in the ophthalmologic field. Accordingly, if the
initiation time of dry spot (the time elapsed until the appearance
of dry spot) is short, many dry spots are observed, the size of dry
spot is large, or the like, it can be said that the eye is more
dried. The result of this test showed that the total areas of dry
spot for the formulations of Examples were remarkably smaller than
those for the formulations of Comparative Examples. Thus, by the
formulations of Examples, it can be said that the tear film on the
surface of contact lens was stabilized and dry spot was difficult
to form. Also, this fact showed that desiccation of eye was
suppressed remarkably, thus a symptom of dry eye was improved.
(2) Evaluation of the Area of Dry Spot--2
[0107] The wetting solution--eye drops for contact lenses was
subjected to the usage as a contact lens wetting solution under the
condition as described above, and then, the solution was applied to
eyes while wearing contact lenses, followed by the evaluation of
the area of dry spot under the following condition.
[0108] In the dry eye observation instrument (DR-1), the area of
the dry spot of the maximum size, which was observed between the
beginning of a blinking at about 11 minutes after the application
to eyes and the beginning of the next blinking was analyzed by the
image analyzer, and then the area ratio (%) to the whole area
observed on the eye surface was calculated. About 11 minutes after
the application of eye drops, eye dryness was progressed especially
in the case of the formulations of Comparative Examples and thus
dry spot was observed as a single comprehensive form of dry area.
The average total score of the three subjects and a relative value
of an area ratio for each formulation was calculated by defining
the area ratio of Example 1 as the value of 1. The result is shown
in Table 6 as "Evaluation-2 for the Area of Dry Spot".
TABLE-US-00006 TABLE 6 Soft Evalu- Evaluation of area of dry spot
contact ation Ex. Comp. Comp. Ex. Ex. Ex. Ex. Ex. lens Item 1 1 2 2
3 4 5 6 SCL1 Area 6.0 68.3 91.7 7.7 11.7 9.0 6.7 31.0 ratio
Relative 1.0 11.4 15.3 1.3 2.0 1.5 1.1 5.2 value SCL2 Area 5.3 69.0
54.3 3.3 10.0 6.0 28.3 32.7 ratio Relative 1.0 13.0 10.2 0.6 1.9
1.1 5.3 6.2 value
[0109] As aforementioned, when the size of dry spot is large, it
can be said that eye is under more dryness condition. The result of
this test showed that even after a sufficient time passed from the
application to eyes, the area ratios of dry spot for the
formulations of Examples are small, which means that the tear film
on the surface of contact lens is stabilized and that dryness of
eye is suppressed remarkably. Also, this result shows an
improvement in a symptom of dry eye.
(3) Evaluation of Stability of Tear Fluid
[0110] The wetting solution--eye drops for contact lenses was
subjected to the usage as a contact lens wetting solution under the
condition as described above, and then, the solution was applied to
eyes while wearing contact lenses, followed by the evaluation of
the stability of the tear fluid under the following condition.
[0111] The movement of the tear fluid lipid layer between the
beginning of blinking at about 3 minutes after the application to
eyes and the next blinking was observed on the dry eye observation
instrument (DR-1), and then was evaluated with a score according to
the criteria described in Table 7. Similarly, the movement of the
tear fluid lipid layer before the application to eyes was evaluated
with a score. Here, a higher score represents that the lipid layer
of the tear film became thin or inhomogeneous, thus the tear film
became unstable. The difference of the score before and after the
application to eyes was considered as an improvement degree of tear
fluid stability, and was evaluated according to the criteria
described in Table 8. The results of the average score for the
three subjects were shown in Table 9.
TABLE-US-00007 TABLE 7 Criteria Score Color is off-white and there
is no movement of 1 point tear film that can be observed. Color is
off-white or yellow, and after blinking 2 points tear film spreads
from lower eyelid to lower pupillary border. There is a slight
disorder in color, contrast or movement of tear film. Color is
off-white or yellow, and after blinking 3 points tear film spreads
from lower eyelid to lower pupillary border. There is a disorder in
color, contrast or movement of tear film. Color consists of an area
of off-white or yellow 4 points and partially an area showing
interference color such as red and green. Dry spot is emerged.
Color consists of a mixture 5 points of an area of off-white or
yellow and one or more areas showing interference color such as red
and green. Dry spot is widely spread. Color consists of 6 points a
mixture of an area of off-white or yellow and one or more areas
showing interference color such as red and green.
TABLE-US-00008 TABLE 8 An improvement degree Criteria of tear fluid
stability No change or worse compared to the not good score before
the application to eyes Improvement by 1 point compared to moderate
the score before the application to eyes Improvement by 2 points
compared to good the score before the application to eyes
Improvement by 3 points and more very good compared to the score
before the application to eyes
TABLE-US-00009 TABLE 9 Soft Improvement degree of tear fluid
stability contact Ex. Comp. Comp. Ex. Ex. Ex. Ex. Ex. lens 1 1 2 2
3 4 5 6 SCL1 very good moder- very very very good good good ate
good good good SCL2 very moder- good very good very good good good
ate good good
[0112] According to the results of the above tests, it was found
that for the formulations of Examples, the lipid layer of the tear
film was hardly disordered and thus remained stable, while for the
formulations of Comparative Examples, the lipid layer of the tear
film easily got disordered and became unstable. As aforementioned,
it is known that as the lipid layer of tear film becomes thinner,
evaporation of tear fluid is promoted and the eye has a tendency to
get dried. Thus the above results show that desiccation of eye was
suppressed remarkably for the formulations of Examples compared to
the formulations of Comparative Examples. Also, this result shows
an improvement of a symptom of dry eye.
Test 2: Evaluation of the Sensation in Using the Solution
[0113] Ten subjects were evaluated for the following criteria.
After wetting both sides of a contact lens with each one drop of
the wetting solution--eye drops, and then the contact lens was
fitted. The same wetting solution--eye drops was applied at two
minutes after wearing, and sensations in using including a
sensation of adstriction (harsh sensation), favorability on a
sensation of coolness and a sensation of dryness were scored
according to the criteria described in Table 10, 11 and 12
respectively. The average scores of the subjects were evaluated
based on the criteria described in Table 13, then the result was
shown in Table 14.
TABLE-US-00010 TABLE 10 Criteria Score Unpleasant sensation of
astriction 1 point Rather unpleasant sensation of astriction 2
points Little sensation of astriction 3 points No sensation of
astriction 4 points
TABLE-US-00011 TABLE 11 Criteria Score Much complaint because of
too strong (or too 1 point weak) sensation Some complaint because
of rather too strong 2 points (or too weak) sensation Almost
satisfied 3 points Very satisfied 4 points
TABLE-US-00012 TABLE 12 Criteria Score High sensation of dryness 1
point Moderate sensation of dryness 2 points Slight sensation of
dryness 3 points No sensation of dryness 4 points
TABLE-US-00013 TABLE 13 Criteria Evaluation 1 point not good More
than 1 point and not more than 2 points moderate More than 2 points
and not more than 3 points good More than 3 points and not more
than 4 points very good
TABLE-US-00014 TABLE 14 Sensation of astriction/Favorability on
Criteria: sensation of coolness/Sensation of dryness evaluation for
Ex. Comp. Comp. Ex. Ex. Ex. Ex. Ex. sensation in using 1 1 2 2 3 4
5 6 Sensation of astriction very moderate moderate very very good
very good (SCL1) good good good good Sensation of astriction very
good good very very very good very (SCL2) good good good good good
Favorability on very not good moderate very very very very very
sensation of coolness good good good good good good (SCL1)
Favorability on very moderate moderate very very very very very
sensation of coolness good good good good good good (SCL2)
Sensation of dryness very not good not good very very very very
very (SCL1) good good good good good good Sensation of dryness very
moderate not good very very very very very (SCL2) good good good
good good good
[0114] According to the above test results, for the formulations of
Examples, a sensation of adstriction (harsh sensation) and a
sensation of dryness as subjective symptoms were suppressed
remarkably, and favorability on a sensation of coolness was also
high.
Test 3: Corroborative Analysis on Usefulness in a Combination of
the Formulations
[0115] Eye drops, contact lens wetting solutions or wetting
solution--eye drops for contact lenses of the formulation 1, 2 and
3 respectively was prepared by the formulations of Table 15
according to a usual preparative method (conventional method) of
eye drops and the like, and were filled in polyethylene
terephthalate containers (volume 10 mL) and were plugged with
nozzles and caps. Unless stated otherwise, the test methods were
similar to the above Test 1 and Test 2 and then the corroborative
analyses on usefulness in a combination of the formulations were
conducted. The result is shown in Table 16. Here, the formulation 1
and the formulation 3 are the formulations of the ophthalmic
compositions of the present invention, and specifically, the same
formulation was used for the formulation 1 and Example 1 in Table
1, and also for the formulation 3 and Example 4 in Table 1
respectively. Also, the same formulation was used for the
formulation 2 and Comparative Example 3 in Table 1.
TABLE-US-00015 TABLE 15 Form. Form. Form. 1 2 3 HPMC .sup.1) 0.2 --
-- Polyvinyl pyrrolidone -- -- 2.5 K90 l-Menthol 0.005 -- 0.002
Sodium chloride 0.44 0.44 0.44 Potassium chloride 0.08 0.08 0.08
Polysorbate 80 0.05 -- 0.05 Boric acid 1.0 1.0 1.0 Borax 0.2 0.2
0.2 Edetate sodium 0.05 0.05 0.05 Purified water q.s. q.s. q.s.
Total volume 100 mL 100 mL 100 mL pH 7.3 7.3 7.3 Osmolality ratio
1.2 1.2 1.2 .sup.1) Hydroxypropyl methylcellulose 2906 (trade name:
65SH-4000 (Shin-Etsu Chemical. Co., Ltd.)
TABLE-US-00016 TABLE 16 Ex. 1 Comp. 1 Comp. 2 Comp. 3 Timing of
application Fitting Application Fitting Application Fitting
Application Fitting Application to eyes to eyes to eyes to eyes
Formulation 1 1 1 2 2 1 2 2 Dosage form.sup.1) Wetting Wetting
Wetting Eye drops Wetting Eye drops Wetting Wetting solution -
solution - solution solution solution - solution - eye drops eye
drops eye drops eye drops Evaluation of the 1.0 6.1 3.5 4.8 area of
dry spot - 1 Analysis B (SCL1) Evaluation of the 1.0 15.3 4.9 7.6
area of dry spot - 1 Analysis B (SCL2) Evaluation Area 6.0 85.0
72.7 66.0 of the area ratio of dry spot - Relative 1.0 14.2 12.1
11.0 2 (SCL1) value Evaluation Area 5.3 88.7 82.7 95.0 of the area
ratio of dry spot - Relative 1.0 16.7 15.6 17.9 2 (SCL2) value
Improvement of very good moderate good not good stability of tear
fluid (SCL1) Improvement of good moderate moderate not good
stability of tear fluid (SCL2) Sensation of very good moderate
moderate not good astriction (SCL1) Sensation of very good good
moderate not good astriction (SCL2) Favorability on very good
moderate moderate not good sensation of coolness (SCL1)
Favorability on very good moderate good not good sensation of
coolness (SCL2) Sensation of dryness very good not good not good
not good (SCL1) Sensation of dryness very good not good not good
not good (SCL2) Ex. 2 Comp. 4 Comp. 5 Timing of application Fitting
Application Fitting Application Fitting Application to eyes to eyes
to eyes Formulation 3 3 3 1 1 3 Dosage form.sup.1) Wetting Wetting
Wetting Eye drops Wetting Eye drops solution - solution - solution
solution eye drops eye drops Evaluation of the 1.2 3.6 1.9 area of
dry spot - 1 Analysis B (SCL1) Evaluation of the 0.9 4.9 6.3 area
of dry spot - 1 Analysis B (SCL2) Evaluation Area 25.0 54.3 33.7 of
the area ratio of dry spot - Relative 4.2 9.1 5.6 2 (SCL1) value
Evaluation Area 7.7 64.0 43.7 of the area ratio of dry spot -
Relative 1.5 12.1 8.2 2 (SCL2) value Improvement of very good good
moderate stability of tear fluid (SCL1) Improvement of very good
moderate moderate stability of tear fluid (SCL2) Sensation of good
moderate good astriction (SCL1) Sensation of very good moderate
moderate astriction (SCL2) Favorability on very good good good
sensation of coolness (SCL1) Favorability on very good moderate
good sensation of coolness (SCL2) Sensation of dryness very good
moderate good (SCL1) Sensation of dryness very good moderate
moderate (SCL2) .sup.1)Terms: "Wetting solution" and "Wetting
solution - eye drops" represent "Contact lens wetting solution" and
"Wetting solution - eye drops for contact lenses",
respectively.
[0116] When the cases of using the formulation of the present
invention as a wetting solution--eye drops for contact lenses
(Practical Test Examples 1 and 2) are compared with the case of
using the different formulation from that of the present invention
as a wetting solution--eye drops for contact lenses (Comparative
Test Example 3), Practical Test Examples 1 and 2 showed higher
stability of the tear fluid lipid layer and remarkably smaller
score in the evaluation for the area of dry spot, resulting in
giving remarkably higher suppression of dryness of eyes.
Additionally, an advantageous effect was found on a sensation of
adstriction and a sensation of dryness as subjective symptoms.
Further, an advantageous effect was shown on the favorability on a
sensation of coolness. Furthermore, even though the formulations
used were within the scope of the composition of the present
invention, the case in which the same composition was used as the
wetting solution--eye drops for contact lenses to the same contact
lens or the eyeball at the time of fitting and application to eyes
(Practical Test Examples 1 and 2) was compared with the case in
which different compositions were used at the time of fitting and
applying to eyes (Comparative Test Examples 4 and 5), Practical
Test Examples 1 and 2 showed remarkably advantageous effect.
Test 4: Evaluation of the Improvement Effect on Eye Strain
(Test Method)
[0117] The improvement effect on eye strain was evaluated with the
wetting solution--eye drops for contact lenses of the formulation 1
in Table 15 (which was the same as Example 1). Flicker fusion
threshold was used as an index of the evaluation.
[0118] Specifically, four subjects who had worn contact lenses for
five days and more in a week and were susceptible to eye strain
wore contact lenses for eight hours and more in a day, and
thereafter flicker fusion threshold in a condition of wearing
contact lenses (flicker fusion threshold before dosing) were
measured. The contact lens used by the subjects were (1) soft
contact lens Group IV Johnson & Johnson K. K., main material:
Senofilcon A (silicone-hydrogel material); (2) soft contact lens
Group IV Johnson & Johnson K. K., main material: Etafilcon A;
and (3) oxygen permeable hard contact lens.
[0119] Then after a sufficient time has passed, the contact lenses
were once removed from both eyes, and each one drop of the wetting
solution--eye drops for contact lenses of the formulation 1 was
added dropwise directly into the concave face (the inside face,
which contacts with cornea) of the contact lens, the contact lenses
were fitted again to both eyes, and after fifteen minutes, each one
drop of the wetting solution--eye drops for contact lenses of the
formulation 1 was applied to both eyes, and thereafter flicker
fusion threshold (flicker fusion threshold after dosing) was
measured (Practical Test Example 3).
[0120] On the other day, the flicker fusion threshold before dosing
was measured in a similar manner and the eye drops of the
formulation 1 was applied in one drop each to both eyes while
wearing contact lenses, and after 15 minutes, eye drops for contact
lenses of the formulation 1 was applied in one drop each to both
eyes again and then flicker fusion threshold (flicker fusion
threshold after dosing) was measured (Comparative Test Example 6).
An improvement rate of flicker fusion threshold was calculated
using the obtained flicker fusion threshold according to the
equation 1 given below.
[0121] The flicker fusion threshold represents critical frequency
at which a flickering light appears to be steady to the eye as the
flickering frequency of the light is gradually increased. Flicker
value can be used as an index to determine eye strain or loss of
sensory function. In other words, an improvement of the flicker
fusion threshold is an index of an improvement of eyestrain (in
particular, eye strain caused by physical or mental fatigue
accompanied by loss of sensory function) or asthenopia.
[0122] In this test, the flicker fusion threshold was measured with
an instrument and a condition as described below.
[0123] Instrument: Roken digital flicker RDF-1 (Shibata Scientific
Technology Ltd.);
[0124] Illuminance: The illuminance was set to the value that can
be easily observed by a measurer;
[0125] Distance: The distance was set to the position that can be
easily observed by a measurer (a position at which "K" character
can be seen most clearly by a measurer);
[0126] SCAN knob (initial flicker frequency to be descended): 60
Hz;
[0127] MANU-AUTO: Set to AUTO.
[0128] The obtained flicker fusion threshold was used for
calculating the value of the improvement of eye strain (an
improvement rate of flicker fusion threshold) according to the
following equation 1:
Improvement rate of flicker fusion threshold (%)=(Flicker fusion
threshold after dosing (Hz)-Flicker fusion threshold before dosing
(Hz))/Flicker fusion threshold before dosing (Hz).times.100
[Equation 1]
[0129] The average of the results for four subjects is shown in
Table 17. According to this result, for all the four subjects a
remarkable increase in the improvement rate of flicker fusion
threshold was observed in Practical Test Example 3 compared to
Comparative Test Example 6. In this field of the art, it is
normally thought that whether an effect (clear change) is present
or not is judged based on the level of about 3% of the improvement
rate of flicker fusion threshold. According to the above results,
it was confirmed that the wetting solution--eye drops for contact
lenses of the present invention was remarkably superior in an
improvement effect on eye strain, asthenopia, or physical or mental
fatigue, and thus is very useful as compared to the usage only as
eye-drops like a conventional use of eye drops.
TABLE-US-00017 TABLE 17 Practical Test Example 3 Comp. Test Example
6 (fitting + (application to eyes + application to eyes)
application to eyes) Improvement rate of 4.2 1.8 flicker fusion
threshold (%)
Examples 7 to 11
[0130] The wetting solution--eye drops for contact lenses (Examples
7 to 11) were prepared according to the formulations described in
Table 18. The unit for each ingredient to be compounded in Table 18
is g/100 mL. All these Examples showed similar effects of the
invention as Example 1 in the above Tests 1 to 4.
TABLE-US-00018 TABLE 18 Ex. Ex. Ex. Ex. Ex. 7 8 9 10 11 HPMC
.sup.1) -- -- -- 0.2 0.2 Hydroxyethyl- 0.2 0.6 -- -- -- cellulose
.sup.2) Polyvinyl alcohol -- -- -- -- 1 (partially saponified
product) Dextran 70 -- -- 0.1 -- -- Macrogol 4000 -- -- -- 1 --
l-Menthol 0.01 0.01 0.005 -- 0.015 d-Camphor -- -- 0.001 -- 0.01
Peppermint oil -- -- -- 0.002 -- Geraniol -- -- 0.005 -- -- Mint
oil -- -- -- 0.002 -- Bergamot oil -- -- -- -- 0.002 Polysorbate 80
0.1 -- -- -- 0.3 POE hydrogenated -- 0.05 0.05 0.3 -- castor oil 60
Poloxamer 407 -- -- -- -- 0.1 Sodium chloride 0.44 0.22 0.44 0.44
0.44 Potassium chloride 0.08 0.08 0.08 0.08 0.08 Boric acid 1 1 1 1
-- Borax 0.2 0.2 0.2 0.2 -- Sodium dihydrogen -- -- -- -- 0.25
phosphate Disodium hydrogen -- -- -- -- 0.05 phosphate Edetate
sodium 0.05 0.05 0.05 0.05 0.05 Polyhexanide -- -- -- -- 0.0001
hydrochloride Purified water q.s. q.s. q.s. q.s. q.s. Total volume
100 mL 100 mL 100 mL 100 mL 100 mL pH 7.3 7.3 7.3 7.3 6.5
Osmolality ratio 1.2 1.0 1.2 1.2 0.7 Viscosity (mPa s) 3.5 60 1.1 3
4 .sup.1) Hydroxypropyl methylcellulose (trade name: 65SH-4000
(Shin-Etsu Chemical. Co., Ltd.) .sup.2) Trade name: CF-V Sumitomo
Seika Chemicals Co., Ltd.
Test 5: Evaluation of an Improvement Effect on Contrast
Sensitivity
(Test Method)
[0131] An improvement effect on contrast sensitivity was evaluated
using the wetting solution--eye drops for contact lenses of
Examples 1 to 11 in Table 1 and Table 18.
[0132] Specifically, the contrast sensitivity was measured for the
eight subjects who had worn contact lens for five days and more a
week in a condition of wearing contact lens by using Vision
Contrast Test System (VCTS (trademark)) Chart Test (as a blank). A
detailed evaluation method was referred to the instruction (VCTS
Chart Examination Procedure, Vistech Consultants, Inc.) packaged
with the VCTS Chart Test. Also the contrast sensitivity value was
calculated by using a table of Contrast Sensitivity Value Key in
the said instruction. The scores included five points of A (1.5 cpd
(i.e. cycles/deg)), B (3 cpd), C (6 cpd), D (12 cpd) and E (18
cpd).
[0133] Firstly, the wetting solution--eye drops for contact lenses
of the formulation 1 in Table 15 (which is the same as Example 1)
was subjected to the usage as a contact lens wetting solution, and
after two minutes, the same solution was applied to eyes while
wearing contact lens, then after one minute the contrast
sensitivity was measured (Practical Test Example 4). Four subjects
wore the contact lenses of the above SCL1, and the other four
subjects wore SCL2.
[0134] The average of the results obtained from eight subjects is
shown in FIG. 1. According to this result, for all the eight
subjects, Practical Test Example 4 wherein the formulation 1 was
used as the wetting solution--eye drops for contact lenses showed
remarkable improvement in contrast sensitivity compared to the
blank.
[0135] Similarly, for the wetting solution--eye drops for contact
lenses prepared according to Examples 2 to 11, the contrast
sensitivity in the point of B (3 cpd), at which there was the
biggest difference between Examples and the blank, were measured
and the average of the result is shown in Table 19. Ten subjects
wore the contact lens of the above SCL1, and the other 10 subjects
wore SCL2.
TABLE-US-00019 TABLE 19 Ex. Ex. Ex. Ex. Ex. Ex. Ex. Ex. Ex. Ex. Ex.
Blank 1 2 3 4 5 6 7 8 9 10 11 con- SCL1 29 54 62 48 59 49 42 60 56
53 55 55 trast sen- SCL2 34 54 65 44 65 44 44 54 58 65 51 65 sitiv-
ity
[0136] As is evident from the above result, the use of the wetting
solution--eye drops for contact lenses of Examples 2 to 11 also
exhibited remarkable improvement in contrast sensitivity compared
to the blank, in the same manner as Example 1.
Formulation Example 1 to 10
[0137] The wetting solution--eye drops for contact lenses
(Formulation Example 1 to 10) were prepared according to the
prescriptions described in Table 20. The unit for each ingredient
to be compounded in Table 20 is g/100 mL.
TABLE-US-00020 TABLE 20-1 Form. Form. Form. Form. Form. 1 2 3 4 5
HPMC .sup.1) 0.01 0.2 -- -- -- Hydroxyethyl- -- -- 0.05 0.4 0.01
cellulose .sup.2) Polyvinyl alcohol -- -- 2 -- -- (partially
saponified product) Polyvinylpyrrolidone 2.5 -- -- 1.5 -- K90
Carboxy vinyl polymer -- 0.2 -- -- 0.2 l-Menthol 0.01 0.005 0.015
0.004 -- d-Camphor 0.008 0.005 0.010 -- -- Peppermint oil -- -- --
0.005 -- Geraniol -- -- -- -- 0.005 Bergamot oil -- -- -- -- 0.002
Polysorbate 80 0.05 -- -- -- 0.1 POE hydrogenated 0.05 0.5 0.1 0.2
-- castor oil 60 Potassium magnesium -- 1 -- -- -- aspartate
Epsilon-aminocaproic -- -- -- 2 -- acid Sodium chloride 0.44 0.22
0.44 0.44 0.3 Potassium chloride 0.08 0.08 0.08 0.08 0.08 Boric
acid 1 1 -- 1.8 1 Borax 0.2 0.2 -- 0.2 0.2 Disodium hydrogen -- --
0.3 -- -- phosphate.cndot.12 hydrates Sodium dihydrogen -- -- 0.02
-- -- phosphate.cndot.2 hydrates Edetate sodium 0.05 0.05 0.05 0.01
0.2 Polyhexanide -- 0.0001 -- -- -- hydrochloride Potassium sorbate
-- -- 0.1 -- -- Purified water q.s. q.s. q.s. q.s. q.s. Total
volume 100 mL 100 mL 100 mL 100 mL 100 mL pH 7.3 7.3 6.5 7.3 7.3
Osmolality ratio 1.2 1.0 1.3 1.6 1.1 Viscosity (mPa s) 1.8 15 2.5
20 15 .sup.1) Hydroxypropyl methylcellulose (trade name: 65SH-4000
(Shin-Etsu Chemical. Co., Ltd.) .sup.2) Trade name: CF-V Sumitomo
Seika Chemicals Co., Ltd.
TABLE-US-00021 TABLE 20-2 Form. Form. Form. Form. Form. 6 7 8 9 10
HPMC .sup.1) -- -- -- -- 0.1 Hydroxyethyl- -- -- -- -- 0.1
cellulose .sup.2) Carboxymethyl- 0.4 -- -- -- 0.4 cellulose sodium
.sup.3) Methylcellulose .sup.4) -- 0.4 -- -- -- Polyvinyl alcohol
-- -- 1.2 -- -- (partially saponified product) Polyvinylpyrrolidone
-- -- -- 2 1 K90 Dextran 70 0.1 -- -- -- -- Macrogol 4000 -- 1 --
-- -- l-Menthol -- 0.01 -- 0.001 0.01 d-Camphor -- 0.005 -- -- --
Peppermint oil -- -- 0.01 -- -- Geraniol -- 0.001 -- -- -- Mint oil
0.01 -- -- 0.003 -- Polysorbate 80 -- 0.005 0.5 -- 0.05 POE
hydrogenated 0.005 -- -- 0.05 -- castor oil 60 Poloxamer 407 -- --
-- 0.05 0.1 Potassium aspartate -- -- 1 1 -- Potassium magnesium --
0.2 -- -- -- aspartate Aminoethylsulfonic 1 -- -- -- 1 acid
Pyridoxine -- -- 0.1 -- -- hydrochloride Sodium hyaluronate -- --
-- 0.005 0.001 Sodium chloride 0.44 0.44 0.44 0.44 0.44 Potassium
chloride 0.08 0.08 0.08 0.08 0.08 Sodium hydrogen -- -- -- 0.4 --
carbonate Calcium chloride -- -- -- 0.005 -- Boric acid 1 1 -- 1 1
Borax 0.2 0.2 -- 0.2 0.2 Disodium hydrogen -- -- 0.3 -- --
phosphate.cndot.12 hydrates Sodium dihydrogen -- -- 0.02 -- --
phosphate.cndot.2 hydrates Edetate sodium 0.05 0.05 0.05 0.05 0.05
Polyhexanide -- 0.00005 -- -- -- hydrochloride Potassium sorbate --
0.1 -- -- -- Purified water q.s. q.s. q.s. q.s. q.s. Total volume
100 mL 100 mL 100 mL 100 mL 100 mL pH 7.3 7.3 6.5 7.3 7.3
Osmolality ratio 1.5 1.2 1.3 1.5 1.5 Viscosity (mPa s) 11 14 2 5 18
.sup.1) Hydroxypropyl methylcellulose (trade name: 65SH-4000
(Shin-Etsu Chemical. Co., Ltd.) .sup.2) Trade name: CF-V Sumitomo
Seika Chemicals Co., Ltd.. .sup.3) Trade name: AG Gum M Dai-ichi
Kogyo Seiyaku Co., Ltd. .sup.4) Trade name: SM8000 Shin-Etsu
Chemical. Co., Ltd.
Industrial Applicability
[0138] The ophthalmic composition of the present invention can
stabilize the tear film during wearing contact lens, suppress eye
dryness, impart a favorable sensation in using, is highly
convenient with no risk of misuse and shows a high efficiency in
the course from manufacturing to sales, which therefore are very
useful in the industry.
* * * * *