U.S. patent application number 09/901909 was filed with the patent office on 2002-02-21 for preventive, alleviative or remedy for hypertension.
This patent application is currently assigned to KAO CORPORATION. Invention is credited to Eguchi, Yasuteru, Mitsui, Yuki, Okawa, Wataru, Suzuki, Atsushi, Takahashi, Hirokazu, Watanabe, Takuya.
Application Number | 20020022062 09/901909 |
Document ID | / |
Family ID | 18707066 |
Filed Date | 2002-02-21 |
United States Patent
Application |
20020022062 |
Kind Code |
A1 |
Okawa, Wataru ; et
al. |
February 21, 2002 |
Preventive, alleviative or remedy for hypertension
Abstract
Provided is a preventive, ameliorant or remedy for hypertension
excellent in both blood pressure lowering action and blood
pressure-rise suppressing action and having high safety. This
preventive, ameliorant or remedy for hypertension comprises a
coffee bean extract.
Inventors: |
Okawa, Wataru; (Sumida-Ku,
JP) ; Mitsui, Yuki; (Sumida-Ku, JP) ;
Watanabe, Takuya; (Sumida-Ku, JP) ; Eguchi,
Yasuteru; (Sumida-Ku, JP) ; Takahashi, Hirokazu;
(Sumida-Ku, JP) ; Suzuki, Atsushi; (Haga-gun,
JP) |
Correspondence
Address: |
OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC
FOURTH FLOOR
1755 JEFFERSON DAVIS HIGHWAY
ARLINGTON
VA
22202
US
|
Assignee: |
KAO CORPORATION
Chuo-ku
JP
|
Family ID: |
18707066 |
Appl. No.: |
09/901909 |
Filed: |
July 11, 2001 |
Current U.S.
Class: |
424/776 |
Current CPC
Class: |
A61K 36/74 20130101;
A61P 9/12 20180101; A23L 23/00 20160801; A61K 36/74 20130101; A61P
9/02 20180101; A23F 5/02 20130101; A61K 2300/00 20130101; A23F 5/24
20130101 |
Class at
Publication: |
424/776 |
International
Class: |
A61K 035/78 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 12, 2000 |
JP |
2000-210865 |
Claims
1. A preventive, ameliorant or remedy for hypertension, which
comprises a coffee bean extract.
2. A preventive, ameliorant or remedy for hypertension according to
claim 1, wherein the coffee bean extract is the extract of raw
coffee beans.
3. A preventive, ameliorant or remedy for hypertension according to
claim 1, wherein the coffee bean extract contains a chlorogenic
acid and caffeine at a chlorogenic acid/caffeine weight ratio of 2
or greater.
4. A preventive, ameliorant or remedy for hypertension according to
claim 3, wherein the chlorogenic acid/caffeine weight ratio ranges
from 2 to 1000.
5. A food comprising a preventive, ameliorant or remedy for
hypertension as claimed in any one of claims 1 to 4.
6. A method for treating hypertension, which comprises
administering an effective amount of a coffee bean extract.
Description
TECHNICAL FIELD
[0001] The present invention relates to a preventive, alleviative
or remedy for hypertension which has excellent blood pressure
lowering effects, blood-pressure-rise suppressing effects and
safety and is available in the form of a food or
pharmaceutical.
BACKGROUND ART
[0002] Examples of a pharmaceutical used for treatment of
hypertension include various neuroleptics acting on the
neural-factor-related regulator system, ACE inhibitors acting on
the heurohumoral-factor-relate- d regulator system, AT receptor
antagonists, Ca antagonists acting on the
vascular-endothelium-derived-substance-related regulator system,
and hypotensive diuretics acting on the body-fluid-regulator system
in the kidney. These pharmaceuticals are mainly used in medical
institutions for patients suffering from severe hypertension.
[0003] Under the present state, however, pharmaceuticals used as a
measure against hypertension are a serious burden for patients
because in spite of satisfactory effectiveness, their side effects
are not a few.
[0004] In the case where hypertension is regarded as a life-style
related disease, on the other hand, general therapies for improving
the life style such as dietetic therapy, kinesitherapy and
limitation of alcoholic intake or smoking are applied widely not
only to the people having a high normal blood pressure including a
mild case but also to patients suffering from severe hypertension.
With a tendency to recognize the importance of general therapies,
improvement of eating habits has received great attention. Since
there exist a large number of foods having blood pressure lowering
action, pressure reducing materials derived from foods have so far
been briskly searched for and separation and identification of
their effective ingredients have been carried out frequently.
[0005] Under such situations, there is an increasing demand for the
development of a method for preventing, ameliorating or treating
hypertension without depending on pharmaceuticals if possible. As
such a method, dietetic therapy is particularly important, so that
foods having blood pressure lowering effects or blood-pressure-rise
inhibitory effects have briskly been searched for. Proposed is use
of, as a hypotensor, the juice of an unripe fruit of apples, pears,
peaches or like fruits belonging to the family Rosaceae which juice
contains fruit polyphenol such as caffeic acid having angiotensin I
converting enzyme (ACE) inhibiting action (Japanese Patent
Application Laid-Open (Kokai) No. Hei 8-259453). It is also
reported that a water extract of sugarcane root tuber contains a
chlorogenic acid, which is a polyphenol, and it has ACE inhibitory
action (Food Research Results Information, No. 9, 20-21(1997)).
[0006] Foods which are said to have pressure reducing effects or
their effective ingredients, however, tend to be not always
satisfactory in their effectiveness, intake frequency or taste upon
intake and in addition, many of them do not start exhibition of
blood pressure lowering effects soon after intake.
[0007] An object of the present invention is therefore to provide a
preventive, alleviative or remedy for hypertension which is derived
from plants or foods, has excellent safety, does not become a
burden for patients when administered daily and orally, and has
high antihypertensive action.
DISCLOSURE OF THE INVENTION
[0008] The present inventors have searched for various food- or
plant-derived components useful for the prevention or amelioration
of hypertension. As a result, it has been found that an extract of
coffee beans containing caffeine which is a stimulant has high
pressure reducing action and can suitably be formed into a
pharmaceutical or food.
[0009] In the present invention, there is thus provided a
preventive, ameliorant or remedy for hypertension, which comprises
an extract of coffee beans; and a food containing the extract.
BEST MODE FOR CARRYING OUT THE INVENTION
[0010] The extract of coffee beans to be used in the present
invention is an extract from coffee beans which are fruits of a
coffee tree. As the coffee tree, any one of C. arabica, C. robusta,
C. liberica and C. arabusta is usable.
[0011] As the coffee beans to be extracted in the present
invention, either raw beans or decaffeine treated beans or roasted
beans are usable, with raw beans being particularly preferred.
[0012] Examples of the method for extracting, from coffee beans, an
ingredient effective for the prevention, amelioration or treatment
of hypertension include solvent extraction and supercritical fluid
extraction. The extract obtained from coffee beans may be purified
or may be adjusted by treatment with an ion exchange resin or the
like (for example, Japanese Patent Application Laid-Open (Kokai)
No. Hei 4-145048, Japanese Patent Application Laid-Open (Kokai) No.
Hei 4-145049, etc.).
[0013] Examples of the extracting solvent used for solvent
extraction include water and hydrophilic organic solvents such as
methanol, ethanol, 2-propanol, acetone and methyl ethyl ketone. As
the extracting solvent, a water-containing hydrophilic organic
solvent having a water content of 5 wt. % (which will hereinafter
be called %, simply) or greater, particularly, hydrous ethanol.
[0014] The extract of coffee beans to be used in the present
invention contains various substances such as known already for
example polysaccharides, lipids, chlorogenic acids, proteins,
caffeine, minerals and fatty acids etc. It preferably contains
chlorogenic acids and caffeine at a weight ratio of 2 or greater,
preferably 2 to 1000, more preferably 2.5 to 500, especially 2.5 to
100 from the viewpoints of effects for preventing, ameliorating or
treating hypertension, and sour taste with astringency upon intake.
Caffeine suppresses pungency and chlorogenic-acid-induced sourness,
whereby such a taste is attained. The components of the coffee bean
extract may be adjusted to fall within the above-described range by
the addition of chlorogenic acid or caffeine.
[0015] Examples of the chlorogenic acid include those having
caffeic acid ester-bonded to one or two hydroxy groups, at the 3-,
4- or 5-position of quinic acid. Specific examples include
3-caffeoylquinic acid (chlorogenic acid) having caffeic acid
ester-bonded to the hydroxyl group at the 3-position of quinic
acid; 5-caffeoylquinic acid having caffeic acid ester-bonded to the
hydroxyl group at the 5-position of quinic acid; 4-caffeoylquinic
acid (cryptochlorogenic acid) having caffeic acid ester-bonded to
the hydroxyl group at the 4-position of quinic acid; and
isochlorogenic acids having caffeic acid ester-bonded to two
hydroxyl groups, among hydroxyl groups at the 3-, 4- and
5-positions of quinic acid (ex. 3,5-caffeoylquinic acid). Salts of
them are also embraced in the term "chlorogenic acid" used
herein.
[0016] No particular limitation is imposed on the salts of a
chlorogenic acid insofar as they are pharmaceutically acceptable
salts. Examples include salts of an alkali (alkaline earth) metal
such as sodium, potassium, calcium and magnesium. The chlorogenic
acid exists also as a salt in naturally-occurring substances.
[0017] The preventive, ameliorant or remedy for hypertension
according to the present invention may further contain another
antihypertensive (agents) materials (such as .alpha.-blocker,
.beta.-blocker, .alpha..beta.-blocker, ACE inhibitor, angiotensin
II receptor antagonist, Ca blocker, diuretic, or psychotropic
agent); vitamin (such as Vitamin A, Vitamin B.sub.1, B.sub.2,
B.sub.6, B.sub.12, Vitamin C, Vitamin D or Vitamin E); and another
active ingredient having blood pressure lowering action
[physiologically active substance (ex. high unsaturated fatty acids
of .omega.-3 type such as .alpha.-linolenic acid, EPA or DHA,
triglyceride and/or diglyceride having this fatty acid as a
component fatty acid, catechin which is a tea polyphenol or polymer
thereof, or rutin which is a buckwheat polyphenol), Litchi
Chinensis Sonn., ginkgo tree, Zizyphi Fructus, Polygonati Rhizoma,
Cassiae Semen, Cortinellus shiitake, Momovdicae grosvenori, flowers
of Chrysanthemum morifolium, leaves of Samallanthus sonchifolius,
mulberry leaves, leaves of Banaba (Lagestroemia speciosa), Senpo,
Plantaginis semen, and these extract etc.]
[0018] When used as a medicament, the preventive, ameliorant or
remedy for hypertension according to the present invention can be
formed into an oral administrable composition by adding thereto a
pharmaceutically acceptable carrier. Examples of the oral
administrable composition include tablets, granules, fine
subtilaes, pills, powders, capsules (hard capsules and soft
capsules), troches, chewables and liquid preparations (medical
drink).
[0019] The preventive, ameliorant or remedy for hypertension
according to the present invention is available as a food by adding
thereto another component. Examples include foods in a liquid,
emulsion or paste form such as beverage, soy sauce, milk, yogurt
and miso to which ordinarily employed food additives have been
added; semi-solid foods such as jelly and gummy; solid foods such
as gum, tofu and supplement; powdery foods. Although it is
available in any form, beverages, particularly soft drinks, are
preferred.
[0020] An effective administration amount of the coffee bean
extract of the present invention is preferably 5 to 5000 mg,
especially 10 to 500 mg, a day per adult (weight: 60 kg) in terms
of a chlorogenic acid contained in a dry solid content of the
coffee bean extract.
EXAMPLES
Preparation of the Extract from Coffee Beans
[0021] From "Flavor Holder FH1041" (trade name of a food additive;
product of T. Hasegawa Co., Ltd.; Coffee Bean Extract 3), an eluate
was obtained using a cationic exchange column (for example,
"SK-1B", trade name; product of Mitsubishi Chemical Co., Ltd.),
followed by concentration into Coffee Bean Extract 4. Caffeine was
extracted from the column and the extract was added to the coffee
bean extract for ingredient adjustment, whereby Coffee Bean
Extracts 1 and 2 were prepared.
[0022] The dry solid contents of Coffee Bean Extracts prepared by
the above-described process and amounts of chlorogenic acid and
caffeine contained in them are shown in Table 1.
1 TABLE 1 Chlorogenic acid/ caffeine contained in Dry solid Coffee
Bean Extract content (%) Total (%) Ratio Coffee Bean Extract 1 71
51 1.2 Coffee Bean Extract 2 58 39 2.5 Coffee Bean Extract 3 53 34
4.8 Coffee Bean Extract 4 48 29 28.0
Example 1
[0023] (a) Animals Provided for Test
[0024] Evaluation test was started after blood pressure of each of
male, 12 week old, spontaneously hypertensive rats (SHRs) was
preliminarily measured for successive 7 days by using a
commercially available noninvasive sphygmomanometer for rat
(manufactured by Softlon Co., Ltd.) in order to accustom the rat to
sphygmomanometric operation. These rats were all bred under
conditions (breeding room in a rat region) of room temperature at
25.+-.1.degree. C., humidity of 55.+-.10% RH and illumination for
12 hours (from 7:00 am to 7:00 pm).
[0025] (b) Administration Method and Amount
[0026] As a material to be administered, Coffee Bean Extract 1,
Coffee Bean Extract 2, Coffee Bean Extract 3 and Coffee Bean
Extract 4 were used in Test Group 1, Test Group 2, Test Group 3 and
Test Group 4, respectively. Coffee Bean Extracts 1, 2, 3 and 4 were
each dissolved in 0.85% physiological saline to give a dry solid
content of 100 mg/kg. In Test Group 5, Coffee Bean Extract 1 was
dissolved in 0.85% physiological saline to give a dry solid content
of 150 mg/kg. As a control group, 0.85% physiological saline was
employed. Each of them was forcedly administered p.o. by using a
metal stomach tube. The dosage was 5 ml/rat.
[0027] (c) Test Method
[0028] SHRs which had been fasted overnight were employed for the
test in groups, one group consisting of 6 rats. Systolic blood
pressures of the caudal artery prior to oral administration and 6
hours after administration were measured.
[0029] (d) Statistic Treatment Method
[0030] Measurement results are indicated by mean and standard
error. As a result of Student's t-test, the significant level was
designated as 5% or less.
[0031] Systolic blood pressures prior to oral administration and 6
hours after administration are shown in Table 2. As is apparent
from Table 2, the blood pressure showed a significant decline in
the test groups to which the coffee bean extract had been
administered compared with that in the control group and
improvement was recognized.
2 TABLE 2 Systolic blood pressure (SBP) (mmHg) Prior to Six hours
after Administered administration administration Control group --
196.0 .+-. 2.1 200.6 .+-. 2.1 Test group 1 Coffee Bean Extract 1
198.8 .+-. 1.1 197.4 .+-. 2.3 Test group 2 Coffee Bean Extract 2
200.7 .+-. 1.6 196.0 .+-. 1.6* Test group 3 Coffee Bean Extract 3
201.0 .+-. 1.8 192.6 .+-. 1.3* Test group 4 Coffee Bean Extract 4
200.7 .+-. 1.9 186.8 .+-. 3.9* Test group 5 Coffee Bean Extract 5
198.4 .+-. 2.7 199.4 .+-. 0.8 *The significance level relative to
the control group was 5% or less, meaning existence of a
significant difference.
Example 2
Blood Pressure Reduction Test on Volunteer
[0032] Blood pressure lowering performance of a soft drink beverage
containing Coffee Bean Extract 3 was evaluated by in thirties six
male volunteers by cross matching at 2 weeks intervals.
[0033] 1) Tested Materials and Test Method
[0034] In accordance with Example 7, two soft drinks, one (P) free
of Coffee Bean Extract 3 and the other (S) containing it, were
prepared and they were confirmed to have equal flavor and taste.
While blindfolding, these volunteers took one bottle (100 ml) of
the drink (P) everyday for two weeks and then one bottle (100 ml)
of the drink (S) everyday for 2 weeks, 4 weeks in total, at any
time.
[0035] 2) Measurement of Blood Pressure
[0036] The blood pressure was measured using "HEM609" (trade name),
a blood pressure monitor manufactured by Omron Corporation. In
consideration of variations of blood pressure within a day, blood
pressure was measured, after rest for 10 minutes before
measurement, at a predetermined time of a day, both prior to
drinking and two weeks after starting of drinking.
[0037] The mean blood pressure before the test was 141 mmHg
(systolic).
[0038] A decline in systolic blood pressure two weeks after
drinking is shown in Table 3. It has been recognized that the blood
pressure showed a significant decline in the group taking the soft
drink containing the coffee bean extract of the present
invention.
3 TABLE 3 Soft A decline in systolic blood pressure drink two weeks
after drinking (mmHg) Control P 1.2 .+-. 1.6 Test group S 8.7 .+-.
1.9* *A significance level was 5% or less relative to the control
group, meaning existence of a significant difference.
Example 3
Powdery Food
[0039] Water was added to 47.4% of glucose, 10% of gum arabic, 36%
of dextrin, 2% of citric acid, 1% of Vitamin C and 3.6% of a coffee
bean extract ("Flavor Holder FH1041", trade name; product of T.
Hasegawa Co., Ltd.) to dissolve the latter in the former. The
resulting solution was spray dried by a spray drier. A sufficient
amount of a flavor (lemon flavor) was added to the resulting
powder, followed by uniform mixing. The mixture was dispensed into
10 g portions, whereby powdery food containing the coffee bean
extract as a preventive, ameliorant or remedy for hypertension and
drinkable after dissolved in water or hot water was prepared.
Example 4
Sugar Tablet Candy
[0040] Uniformly mixed were 76.4% of anhydrous glucose
(crystalline), 9% of frost sugar, 4.5% of orange flavor powder, 2%
of guar gum, 2.5% of ascorbic acid, 1.5% of citric acid (crystals),
3.6% of a coffee bean extract ("Flavor Holder FH1041" trade name;
product of T. Hasegawa Co., Ltd.), 0.5% of sucrose fatty acid ester
(HLB 20) and a sufficient amount of a colorant. The resulting
mixture was tableted in a conventional manner into tablets, each
weighing 2 g and having a diameter of 15 mm .phi., whereby sugar
tablet candies having a good taste and containing the coffee bean
extract as a preventive, ameliorant or remedy for hypertension were
prepared.
Example 5
Food Made of Wheat Flour (Cup Cake)
[0041] Using 100 g of soft flour, 100 g of chicken egg, 110 g of
sugar, 25 g of shortening, 35 g of margarine, 2.5 g of baking
powder, 6.0 g of a liquor, 3.6 of a coffee bean extract ("Flavor
Holder FH1041" trade name; product of T. Hasegawa Co., Ltd.) and a
sufficient amount of water, a dough for cup cake was prepared. The
resulting dough was dispensed into 10 cup cake molds, followed by
baking in a conventional manner, whereby cup cakes having a good
taste and containing the coffee bean extract as a preventive,
ameliorant or remedy for hypertension were obtained.
Example 6
Jellies
[0042] After mixing 0.65% of a mixed gelling agent of carrageenan
and locust bean gum, 5.0% of a 50% concentrated juice of
grapefruit, 0.05% of citric acid, 0.05% of Vitamin C and 1.8% of a
coffee bean extract ("Flavor Holder FH1041" trade name; product of
T. Hasegawa Co., Ltd.), the balance of water was added to the
mixture to dissolve the latter in the former. A small amount of a
grapefruit flavor was added. After sterilization by keeping the
mixture at 85.degree. C. for 5 minutes, it was dispensed into 100
ml containers. They were allowed to stand for 8 hours and then
gradually cooled to 5.degree. C. for gelation, whereby jellies
melting well in the mouth, having a fruit taste and good feeling
upon eating and containing the coffee bean extract as a preventive,
ameliorant or remedy for hypertension were obtained.
Example 7
Soft Drink
[0043] Water was added to 13% of inverted fructose/glucose syrup,
0.3% of citric acid, 0.03% of ascorbic acid, 0.02% of sodium
citrate, 0.1% of flavor (lime flavor) and 0.36% of a coffee bean
extract ("Flavor Holder FH1041" trade name; product of T. Hasegawa
Co., Ltd.) to dissolve the latter in the former, whereby 5 liters
of the solution was obtained as a beverage. Into glass bottles,
100-ml portions of the resulting solution were poured, followed by
sterilization in a conventional manner, whereby soft drinks having
a good taste and containing the coffee bean extract as a
preventive, ameliorant or remedy for hypertension were
obtained.
Example 8
Sugarless Drink
[0044] After adding 360 mg of a coffee bean extract ("Flavor Holder
FH1041" trade name; product of T. Hasegawa Co., Ltd.) to, as a
commercially available sugarless drink, Oolong tea (product of
Suntory, Ltd.) and dissolving the former in the latter, the
solution was sterilized in a conventional manner, whereby a
sugarless drink having a good taste and containing the coffee bean
extract as a preventive, ameliorant or remedy for hypertension was
obtained.
Example 9
Medical Vitamin Drink
[0045] To a sufficient amount of purified water were added 800 mg
of taurine, 11000 mg of sucrose, 50 mg of caramel, 30 mg of sodium
benzoate, 5 mg of vitamin B.sub.1 nitrate, 20 mg of Vitamin
B.sub.2, 20 mg of Vitamin B.sub.6, 2000 mg of Vitamin C, 100 mg of
Vitamin E, 2000 I.U. of Vitamin D.sub.3, 20 mg of nicotinic acid
amide and 360 mg of a coffee bean extract ("Flavor Holder FH1041"
trade name; product of T. Hasegawa Co., Ltd.) to dissolve the
latter in the former. After adjustment of pH to 3 with an aqueous
solution of phosphoric acid, purified water was added to give a
total amount of 50 mL. The resulting aqueous solution was
sterilized at 80.degree. C. for 30 minutes, whereby a medical drink
free of a component change after storage, having excellent taste
and flavor and containing the coffee bean extract as a preventive,
ameliorant or remedy for hypertension was obtained.
Example 10
Chewable Tablets
[0046] To 99 parts by weight of chewable tablet powder composed of
15% of a vitamin mixed preparation containing Vitamin B.sub.1
nitrate, Vitamin B.sub.2, Vitamin B.sub.6 and Vitamin C, 59.6% of
frost sugar, 20.9% of dextrin, 3% of sucrose ester, 1.0% of
hydroxypropyl cellulose and 0.5% of flavor, was added 8.6 parts by
weight of a coffee bean extract ("Flavor Holder FH1041" trade name;
product of T. Hasegawa Co., Ltd.). The resulting mixture was
tableted in a conventional manner into tablets, each 0.2 g in
weight, whereby chewable tablets excellent in both taste and flavor
and containing the coffee bean extract as a preventive, ameliorant
or remedy for hypertension were obtained. One dose requires 5
tablets.
Example 11
Soy Sauce
[0047] To a commercially-available salt-reduced soy sauce (100
parts by weight of salt-reduced say sauce produced by Kikkoman
Corporation), 1.8 parts of a coffee bean extract ("Flavor Holder
FH1041" trade name; product of T. Hasegawa Co., Ltd.) was added to
dissolve the latter in the former, followed by sterilization,
whereby a soy sauce free of a problem both in taste and color
compared with the commercially-available salt-reduced say sauce and
containing the coffee bean extract as a preventive, ameliorant or
remedy for hypertension was obtained. The using amount of this say
sauce is about 20 g/day, similar to the ordinarily employed
one.
Capability of Exploitation in Industry
[0048] The preventive, ameliorant or remedy for hypertension
according to the present invention is excellent in both blood
pressure lowering action and blood pressure rise inhibiting action,
and has high safety.
* * * * *