Note: Descriptions are shown in the official language in which they were submitted.
CA 02504439 2005-04-05
SPECIFICATION
External preparation for improving blood flow
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an external preparation for
improving blood flow that comprises proanthocyanidins. More
specifically, the present invention relates to an external preparation
for skin that, when applied to the skin or the mucous membrane,
promotes blood circulation in the area of application.
2. Description of the Related Art
Poor blood circulation in the skin is regarded as a cause of
skin problems such as dullness and unevenness of skin color, and
furthermore, as a cause of chilblains and the condition of being overly
sensitive to the cold. As therapeutic agents for these diseases,
ointments, creams, and the like that contain an oil, a humectant, or the
like that is derived from a plant and less irritating to the skin have
been extensively studied.
As substances for promoting blood circulation that can be used
for these therapeutic agents, for example, plant extracts, such as oils
and fats obtained from the seeds of shea tree, nicotinic acid derivatives,
vitamin E derivatives, and swertia herb extract, are known (e.g.,
Japanese Patent No. 3113706 and Japanese Laid-Open Patent
Publication No. 11-269054).
However, the conventional external preparations for
1
CA 02504439 2005-04-05
improving blood flow have disadvantages such as poor retention of
their effects. Moreover, active components in the external
preparations that can be derived from plants are not clearly identified.
Thus, even if extracts are obtained from the same plant, the resultant
effects of these extracts often vary from each other. Furthermore, the
usage of a chemical substance such as vitamin E for an external
preparation can be limited due to the specific characteristics of the
chemical substance.
Therefore, there is a demand for an external preparation for
skin that provides a superior effect of improving blood flow.
SUMMARY OF THE INVENTION
The inventors of the present invention performed in-depth
research on the external preparation for improving blood flow in view
of the above-described problems and found that, surprisingly, a
superior effect of improving blood flow is obtained by applying
proanthocyanidins to the skin, the mucous membrane, and the like,
and thus, achieved the present invention.
The present invention provides an external preparation for
improving blood flow that comprises a proanthocyanidin.
In one embodiment, the proanthocyanidin is derived from a
bark of pine a fruit or seeds of grape, blueberry, strawberry, avocado,
locust, or cowberry~ barley wheat soybean black soybean cacao an
inner skin of peanuts or leaves of ginkgo.
In a preferred embodiment, the proanthocyanidin comprises at
least 20 wt% of oligomeric proanthocyanidin.
In a more preferred embodiment, the external preparation fox
improving blood flow further comprises a component providing an
effect of improving blood flow and/or a plant extract providing the
2
CA 02504439 2005-04-05
effect of improving blood flow, wherein the component and the plant
extract do not contain the proanthocyanidin.
According to the present invention, an external preparation
for improving blood flow that contains proanthocyanidins is provided.
The external preparation for improving blood flow of the present
invention provides an effect of improving subcutaneous blood
circulation and the like. The proanthocyanidins that are contained in
the external preparation for improving blood flow of the present
invention provide a better effect of improving blood flow than
conventional plant extracts such as swertia herb extract do, and also
the resultant effect continues for a longer period of time.
Furthermore, when the proanthocyanidins contain at least 20 wt% of
OPCs, a further superior effect of improving blood flow can be
achieve d.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a graph showing a change in blood flow improvement
rate over time after application of 0.1 mL of an external preparation for
improving blood flow of the present invention.
Fig. 2 is a graph showing a change in blood flow improvement
rate over time after application of 0.03 mL of the external preparation
for improving blood flow of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Hereinafter, the external preparation for improving blood flow
of the present invention will be described. It should be noted that the
following description is not limiting the present invention, and it is
apparent to those skilled in the art that various alternations can be
made within the scope of the spirit of the present invention.
3
CA 02504439 2005-04-05
In the present invention, proanthocyanidins refer to a group of
compounds that are condensation products having flavan-3-ol and/or
flavan-3,4-diol as a constituent unit and having a degree of
polymerization of 2 or more, and proanthocyanidins also include
extracts derived from raw material plants containing these compounds.
As the proanthocyanidins that are used for the external
preparation for improving blood flow of the present invention,
proanthocyanidins containing a large amount of condensation products
having a low degree of polymerization are preferably used. As the
condensation products having a low degree of polymerization,
condensation products having a degree of polymerization of 2 to 30
(dimer to 30-mer) are preferable, condensation products having a
degree of polymerization of 2 to 10 (dimer to decamer) are more
preferable, and condensation products having a degree of
polymerization of 2 to 4 (dimer to tetramer) are even more preferable.
In this specification, among proanthocyanidins, condensation
products having ffavan-3-ol and/or flavan-3,4-diol as a constituent unit
and having a degree of polymerization of 2 to 4 are referred to as
oligomeric proanthocyanidins (OPCs). OPCs, which are one type of
polyphenol, are potent antioxidants produced by plants, and contained
concentratedly in portions of plant leaves, bark, or skin or seeds of
fruits. More specifically, they are contained in the bark of pine the
fruit or seeds of grape, blueberry, strawberry, avocado, locust, and
cowberry~ barley wheat soybean black soybean cacao the inner skin
of peanuts and the leaves of ginkgo, for example. Moreover, it is
known that OPCs are also contained in cola nuts in West Africa the
roots of Rathania in Peru and Japanese green tea. OPCs are
substances which cannot be produced in the human body.
Proanthocyanidins containing a large amount of OPCs are preferred.
4
CA 02504439 2005-04-05
Among these, in particular, it is preferable to use a pine bark extract.
Among proanthocyanidins, OPCs are especially abundant in pine bark,
and thus, the pine bark extract is preferably used for the
proanthocyanidins in the present invention.
When proanthocyanidins having a high OPC content are used,
a better effect of improving blood flow can be achieved than in the case
where proanthocyanidins having a high degree of polymerization
(having a low OPC content) are used.
Hereinafter, a method for preparing proanthocyanidins will be
described taking a pine bark extract that contains OPCs abundantly as
an example.
As the pine bark extract, an extract from the bark of plant
belonging to Pinales, such as French maritime pine (Pinus martima),
Larix leptolepis, Pinus thunbergii, Pinus densiflora, Pinus parviffora,
Pinus pentaphylla, Pinus koraiensis, Pinus pumila, Pinus luchuensis,
utsukushimatsu (Pinus densiflora form. umbraculifera), Pinus
palustris, Pinus bungeana, and Anneda in ~,luebec, Canada, can be
preferably used. Among these, French maritime pine (Pinus
martima) bark extract is preferable.
French maritime pine refers to maritime pines that grow in a
part of the Atlantic coastal area in southern France. It is known that
the bark of this French maritime pine contains proanthocyanidins,
organic acids, and other bioactive substances, and proanthocyanidins
from the ffavonoid family, which are the main component of the French
maritime pine bark, have a potent antioxidation ability of removing
active oxygen.
The pine bark extract is obtained by extracting the bark of the
above-described pines using water or an organic solvent. When using
water, it is preferable to employ warm water or hot water. In order to
5
CA 02504439 2005-04-05
increase the extraction efficiency, it is preferable to add a salt such as
sodium chloride to the water. As the organic solvent that can be
employed far extraction, an organic solvent that is acceptable for
production of foods or pharmaceuticals can be employed. Examples of
such solvent include methanol, ethanol, 1-propanol, 2-propanol, 1-
butanol, 2-butanol, acetone, hexane, cyclohexane, propylene glycol,
aqueous ethanol, aqueous propylene glycol, methyl ethyl ketone,
glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane,
edible oils or fats, 1,1,1,2-tetraffuoroethane, and 1,1,2-trichloroethene.
The water and the organic solvents may be used alone or in
combination. In particular, hot water, aqueous ethanol, and aqueous
propylene glycol are preferably used.
The method for extracting proanthocyanidins from pine bark
is not particularly limited, and heat extraction or supercritical fluid
extraction can be employed, for example.
Supercritical fluid extraction is a method for performing
extraction using a supercritical fluid. A supercritical fluid is in a state
that is above the liquid-vapor critical point in the phase diagram
showing critical temperature and critical pressure. Examples of
compounds that can be employed as a supercritical fluid include carbon
dioxide, ethylene, propane, and nitrous oxide (laughter gas). Carbon
dioxide is preferably used.
Supercritical fluid extraction includes an extraction step in
which a target component is extracted with a supercritical fluid and a
separation step in which the target component is separated from the
supercritical fluid. In the separation step, any separation process can
be employed, examples of which include a separation based on a
change in pressure, a separation based on a change in temperature,
and a separation using an adsorbent or absorbent.
6
CA 02504439 2005-04-05
Moreover, it is also possible to perform supercritical fluid
extraction in which an entrainer is added. In this method, extraction
is performed using an extracting fluid obtained by adding, for example,
ethanol, propanol, n-hexane, acetone, toluene, or another aliphatic
lower alcohol, aliphatic hydrocarbon, aromatic hydrocarbon, or ketone
at about 2 to 20 W/V% to a supercritical fluid, so that the solubility of a
target substance to be extracted, such as OPCs and catechins
(described later), in the extracting fluid is dramatically increased or
the selectivity of separation is enhanced. Thus, a pine bark extract is
obtained efficiently.
Since supercritical fluid extraction can be performed at a
relatively low temperature, it has the following advantages: it is
applicable for extracting substances that deteriorate or decompose at
high temperatures the extracting fluid does not remain and the
extracting fluid can be recovered and recycled, so that a step of
removing the extracting fluid and the like can be omitted, and thus,
the process can be simplified.
Furthermore, methods other than those mentioned above can
be employed for extraction from pine bark, and examples thereof
include a batch method using liquid carbon dioxide, a reflux method
using liquid carbon dioxide, and a reflux method using supercritical
carbon dioxide.
It is also possible to employ a combination of a plurality of
extraction processes to perform extraction from pine bark. By
combining a plurality of extraction processes, pine bark extracts with
various components can be obtained.
The pine bark extract that is used for the external preparation
for improving blood flow of the present invention is specifically
prepared using the following method. However, this method is merely
7
CA 02504439 2005-04-05
an example, and the pine bark extract used for the present invention is
not limited to the extract obtained by this method.
First, 1 kg of the bark of French maritime pine is immersed in
3 L of a saturated solution of sodium chloride, and extraction is
performed for 30 minutes at 100°C to obtain an extract liquid
(extraction step). Then, the extract liquid is filtrated, and the
resultant insoluble material is washed with 500 ml of a saturated
solution of sodium chloride to obtain a washed liquid (washing step).
The extract liquid and the washed liquid are combined to obtain a
crude extract liquid of pine bark.
Next, 250 ml of ethyl acetate is added to this crude extract
liquid, mixed, and separated to obtain an ethyl acetate layer. This
process is repeated five times, and the obtained ethyl acetate layers are
combined. The resultant ethyl acetate extract is added directly to 200
g of anhydrous sodium sulfate for drying. Then, this ethyl acetate
extract is filtrated, and the filtrated extract is concentrated under a
reduced pressure to a volume of 1/5 of the original filtrated extract.
The concentrated ethyl acetate extract is poured into 2 L of chloroform
and stirred, and the resultant precipitate is recovered by filtration.
Subsequently, this precipitate is dissolved in 100 ml of ethyl acetate,
and then the resultant solution is added to 1 L of chloroform to form a
precipitate. This process is repeated twice, and thus, a washing
process is accomplished. With this method, for example, about 5 g of
pine bark extract containing at least 20 wt°/ of OPCs that have a
degree of polymerization of 2 to 4 and at least 5 wt°/ of catechins can
be obtained.
It is preferable that an extract derived from a raw material
plant, such as a pine bark extract, contains at least 40 wt°/ of
proanthocyanidins. Furthermore, the OPC content in this extract
8
CA 02504439 2005-04-05
derived from a raw material plant is preferably at least 20 wt°/ and
more preferably at least 40 wt°/ .
An extract derived from the raw material plant contains
catechins as well as OPCs. The term "Catechins" is a general term
referring to polyhydroxyflavan-3-ols. As the catechins, for example,
(+)-catechin, (-)-epicatechin, (+)-gallocatechin, (-)-epigallocatechin,
epigallocatechin gallate, and epicatechin gallate are known.
Gallocatechin, afzelechin, and 3-galloyl derivatives of (+)-catechin or
gallocatechin are isolated from natural products, in addition to (+)-
catechin that is called catechin in a narrow sense. Catechins are
known to have a cancer inhibiting ability, an arteriosclerosis
preventing ability, a lipid metabolism disorder inhibiting ability, a
blood pressure elevation inhibiting ability, a thrombosis preventing
ability, an antiallergic ability, an antiviral ability, an antibacterial
ability, a dental caries preventing ability, a halitosis preventing ability,
an intestinal flora normalization ability, an active oxygen or free
radical eliminating ability, an antioxidation ability, and the like.
Moreover, catechins are known to have an antidiabetic ability of
inhibiting an elevation of blood glucose. Furthermore, catechins have
the property of both increasing the solubility in water and being
activated in the presence of OPCs.
It is preferable that catechins are contained in the above-
described extract derived from a raw material plant in a ratio of 5 wt%
or more. Alternatively, it is also preferable that a formulation is
prepared so that it contains a raw material plant extract containing at
least 20 wt% of OPCs and furthermore, contains catechins in a ratio of
5 wt% or more. For example, when the catechin content in a~ pine
bark extract is less than 5 wt%, it is possible to add catechins so that
the catechin content becomes at least 5 wt%. It is most preferable to
9
CA 02504439 2005-04-05
use a pine bark extract containing at least 5 wt% of catechins and at
least 20 wt% of OPCs.
The proanthocyanidin content in the external preparation for
improving blood flow of the present invention is not particularly
limited, but it is preferably 0.0001 wt% to 5 wt%, more preferably
0.001 wt% to 2 wt%, and even more preferably 0.01 wt% to 1 wt%.
When an extract derived from a raw material plant that
contains proanthocyanidins is employed, the amount of
proanthocyanidins can be calculated based on the proanthocyanidin
content in the extract. As such extract derived from a raw material
plant, a pine bark extract is preferable.
When the thus obtained external preparation for improving
blood flow of the present invention is applied to the skin or the mucous
membrane, it promotes blood circulation in the area of application.
The proanthocyanidins contained in the external preparation for
improving blood flow of the present invention provide an excellent
effect of improving blood flow, and the effect is superior to that derived
from conventional plant extracts such as swertia herb extract. Also,
the effect continues for a longer period of time. Furthermore, when
the proanthocyanidins contain at least 20 wt% of OPCs, a further
superior effect of improving blood flow can be achieved.
The inventors of the present invention have reported that an
effect of improving blood flow in the body is achieved by oral
administration of proanthocyanidins (Japanese Patent Application No.
2002-219175). Since the proanthocyanidins have the property of
constricting proteins, it is difficult to consider that when applied to the
skin, the mucous membrane, and the like, the proanthocyanidins are
absorbed topically into the body and improve blood flow. Therefore,
the effect of the present invention would be unexpected.
10
CA 02504439 2005-04-05
Furthermore, when the external preparation for improving
blood flow of the present invention contains a component other than
the proanthocyanidins and that provides the effect of improving blood
flow and/or a plant extract that does not contain proanthocyanidins
and that provides the effect of improving blood flow, these substances
can provide a synergistic effect of improving blood flow with the
proanthocyanidins.
Examples of the component that provides the effect of
improving blood flow include capsaicin and derivatives thereof
carpronium chloride dialkyl monoamine derivatives saponins~
sinigrin~ nicotinic acid and derivatives thereof and their salts and y-
oryzanol. Capsaicine and derivatives thereof, saponins, and nicotinic
acid and derivatives thereof are preferable.
Examples of the plant extract providing the effect of improving
blood flow include capsicum extract, Panax ginseng extract, treason
extract, arnica extract, safflower extract, sophora root extract, and
Japanese pepper extract. Capsicum extract, Panax ginseng extract,
and sophora root extract are preferable.
In order for these components providing the effect of
improving blood flow and/or plant extracts providing the effect of
improving blood flow to achieve the synergistic effect of improving
blood flow with the proanthocyanidins, it is preferable that they are
contained in the external preparation for improving blood flow of the
present invention in a ratio of 0.0001 wt% to 5 wt% and more
preferably 0.001 wt% to 2 wt°/ .
The external preparation for improving blood flow of the
present invention can be widely applied to drugs, quasi-drugs,
cosmetics, toiletries, and the like. For example, skin lotions, facial
creams, milky lotions, creams, packs, hair tonics, hair creams,
11
CA 02504439 2005-04-05
shampoos, hair rinses, hair treatments, body shampoos, facial
cleansers, soaps, foundations, face powders, lipsticks, lip glosses,
rouges, eye shadows, hairdressings, hair restorers, water-based
ointments, oil-based ointments, eye medicines, eyewashes, dentifrices,
mouthwashes, fomentations, and gels are possible.
Moreover, for example, the external preparation for improving
blood flow of the present invention can be contained in a food such as
candy, gum, and gummi and can be applied to the inside of the oral
cavity. Alternatively, the preparation can be contained in a carrier
such as a fomentations and a gel or can be mixed with a crosslinking
agent and can be applied topically. According to such applications,
the rate of sustained release of the preparation can be controlled, and
thus a long-acting administration can be performed.
Examples
Hereinafter, the present invention will be described by way of
examples. However, the present invention is not limited to these
examples.
Example 1
A skin lotion A having the composition shown in Table 1 below
was prepared using an ethanol extract of pine bark (trade name:
Flavangenol, produced by TOYO SHINYAKU Co., Ltd.) containing 40
wt% of proanthocyanidins (OPC content 20 wt% in the extract) and 5
wt% of catechins, glycerin, citric acid, and sodium citrate.
Examples 2 and 3
In Example 2, a skin lotion B having the composition shown in
Table 1 was prepared by further adding a capsicum extract to the skin
12
CA 02504439 2005-04-05
lotion of Example 1. In Example 3, a skin lotion C having the
composition shown in Table 1 was prepared in the same manner as in
Example 1 except that a previously prepared ethanol extract of pine
bark containing 40 wt% of proanthocyanidins (OPC content: 5 wt°/ in
the extract) and 5 wt% of catechins was used in place of the ethanol
extract of pine bark in Example 1.
Comparative Examples 1 to 3
In Comparative Example 1, a skin lotion D having the
composition Shawn in Table 1 was prepared in the same manner as in
Example 1 except that ~ swertia herb extract (Maruzen
Pharmaceuticals Co., Ltd.) was used in place of the ethanol extract of
pine bark in Example 1. In Comparative Example 2, a skin lotion E
having the composition shown in' Table 1 was prepared by further
adding a capsicum extract to the skin lotion of Comparative Example
1. In Comparative Example 3, a skin lotion F having the composition
shown in Table 1 was prepared in the same manner as in Example 1
except that water was used in place of the ethanol extract of pine bark
in Example 1.
Table 1
Examples Comparative
Examples
1 2 3 1 2 3
Skin lotion A B C D E F
Pine bark extract
(OPC content: 0.01 0.01 - - - -
20 wt%)
Pine bark extract
(OPC content -' -" 0.01 - - -
5 wt%)
Swertia herb - - - 0.01 0.01 -
extract
Capsicum extract- 0.001 - - 0.001 -
Glycerin 0.0010.001 0.001 0.001 0.001 0.001
Citric acid 0.05 0.05 0.05 0.05 0.05 0.05
Sodium citrate 0.04 0.04 0.04 0.04 0.04 0.04
Unit: wt%
13
CA 02504439 2005-04-05
The effect of improving blood flow was evaluated in the
following manner using the obtained skin lotions A to F. First, a total
of six marks each measuring 2.0 cm square were previously put on the
forearm of each of ten subjects (healthy persons between the ages of 20
and 50), and the subcutaneous blood flow rate was measured in the
areas of those marks using a rheometer (laser blood perfusion imager
PIM II~ Perimed AB, Sweden) and the resultant value was determined
as a blood flow rate before application of the skin lotions. The average
value of the blood flow rate before application of the akin lotions was
taken as "a".
Next, 0.1 ml of the skin lotions A to F were applied to the
areas of the above-mentioned marks, respectively. Then, the
subcutaneous blood flow rate was measured 0, 0.5, 1, 1.5, and 2 hours
after the application. The average values of the obtained blood flow
rate measured at predetermined times after the application of the skin
lotions were taken as "b".
Based on the obtained average values a and b, the blood flow
improvement rate was calculated using the following formula to
evaluate the effect of improving blood flow:
Blood flow improvement rate (%) = 100 x (b - a)/a
Fig. 1 shows the results.
Referring to the results in Fig. 1, it can be seen that the skin
lotions containing proanthocyanidins provide higher effects of
improving blood flow, and the effects can be retained for a long period
of time compared with those of the other skin lotions. Furthermore, a
comparison between the skin lotions A and C shows that the skin
lotion containing the proanthocyanidins having the higher OPC
content provides a better effect of improving blood flow. Moreover, a
comparison between the skin lotions B and E shows that when a
14
CA 02504439 2005-04-05
component having the effect of improving blood flow other than the
proanthocyanidins is contained in the skin lotion, a synergistic effect of
improving blood flow derived from such component and the
proanthocyanidins can be obtained.
Furthermore, the retention of the effect of improving blood
flow was evaluated in the following manner using the skin lotions A, B,
D, and E. First, a total of four marks each measuring 2.0 cm square
were previously put on the forearm of each of ten subjects (healthy
persons between the ages of 20 and 50), and the blood flow rate before
application of the skin lotions was measured in the same manner as
described above, and the average value a was calculated. Next, 0.03
ml, which was smaller than the amount described above, each of the
skin lotions A, B, D, and E were applied, and the blood flow rate was
measured at predetermined times after the application of the skin
lotions in the same manner as described above, and the average values
b were calculated. Blood flow improvement rate was calculated as
mentioned above by using the average values a and b. Fig. 2 shows
the results.
Referring to the results in Fig. 2, it can be seen that the effect
of improving blood flow of the skin lotions containing
proanthocyanidins continues for a long period of time even when the
concentration is low. Furthermore, when a capsicum extract is
contained in the skin lotions, the effect can continue even further.
Example 4
A cream foundation having the components listed below was
prepared using a pine bark extract (trade name: Flavangenol, produced
by TOYO SHINYAKU Co., Ltd.):
15
CA 02504439 2005-04-05
<Components of the foundation> (The values are in wt%
Pine bark extract 0.05
Triethanolamine 1.2
Sorbitol 2.0
Methyl parahydroxybenzoate small quantity
Pigment (titanium oxide, talc, and fragrance
and kaolin)
15.5
Stearic acid 5.0
Lipophilic glyceryl monostearate2.5
Cetostearyl alchol 1.0
Propylene glycol monolaurate 3.0
Liquid paraffin 7.0
Isopropyl myristate 8.0
Butyl parahydroxybenzoate small quantity
Water 54.5
Example 5
A lip cream having the components listed below was
produced
in the usual manner usingame pine bark extract as in
the s Example 4:
<Components of the lip (The values are in wt%.)
cream>
Pine bark extract 1.0
Ceresin 4.0
Candelilla wax 8.0
Carnauba wax 2.0
Isostearic acid diglyceride40.0
Castor oil 30.0
Glycerin 2.0
Water 13.0
Subjects using this lip cream remarked that the color
or the
16
CA 02504439 2005-04-05
luster of their lips was improved.
Example 6
A hair tonic having the components listedbelow was produced
using the same pine bark extract as
in Example 4:
<Components of the hair tonic> (The
values are in wt/.)
Pine bark extract 0.1
Sophora root extract 0.1
Glycerin 3.0
1-Menthol 0.2
Polyoxyethylene hydrogenated castor 0.2
oil
Ethanol 60.0
Water 36.4
Example 7
A mouth wash having the components listed below was
produced in the usual manner using the same pine bark extract as in
Example 4:
<Components of the mouth wash> (The values are in wt%.)
Pine bark extract 0.01
Panax ginseng extract 0.1
Ethyl alcohol 16.0
Saccharin sodium 0.5
Polyoxyethylene hydrogenated castor oil 2.5
Glycerin 6.0
Flavor small quantity
Water 75.5
Example 8
17
CA 02504439 2005-04-05
A dentifrice having the
components listed below
was prepared
in the usual manner using
the same pine bark extract
as in Example 4:
<Components of the dentifrice>(The values are in wt%.)
Pine bark extract 0.01
Calcium carbonate 39.0
Sorbitol 15.0
Sodium carboxymethylcellulose0.6
Sodium laurate 1.3
Saccharin 0.09
Mint flavor and preservativesmall quantity
Water 43.0
Example 9
An ophthalmic solution (ophthalmic
composition) having the
components listed below was preparedthe usual manner using
in the
same pine bark extract as in Example
4:
<Components of the ophthalmic (The values are in
solution> wt%.)
Pine bark extract 0.01
Tear components
Sodium chloride 0.7
Potassium chloride 0.2
Anti-inflammatory agent
Sodium azulene sulfonate 0.02
Tetrahydrozoline hydrochloride 0.02
Antihistaminic agent
Chlorpheniramine maleate 0.03
Water 99.02
The invention may be embodied in other forms without
18
CA 02504439 2005-04-05
departing from the spirit or essential characteristics thereof. The
embodiments disclosed in this specification are to be considered in all
respects as illustrative and not limiting. The scope of the invention is
indicated by the appended claims rather than by the foregoing
description, and all changes which come within the meaning and range
of equivalency of the claims are intended to be embraced therein.
19
