U.S. patent application number 10/050459 was filed with the patent office on 2003-02-27 for agents for improving lipid metabolism and reducing high blood pressure.
Invention is credited to Abe, Takumi, Kawakami, Hiroshi, Morita, Yoshikazu, Takada, Yukihiro, Toba, Yasuhiro.
Application Number | 20030040475 10/050459 |
Document ID | / |
Family ID | 26607795 |
Filed Date | 2003-02-27 |
United States Patent
Application |
20030040475 |
Kind Code |
A1 |
Toba, Yasuhiro ; et
al. |
February 27, 2003 |
Agents for improving lipid metabolism and reducing high blood
pressure
Abstract
A milk-derived basic protein fraction and a basic peptide
fraction are provided for use as an effective component for agents
for improving lipid metabolism and reducing high blood pressure
which can be administered orally, are effective with a relatively
small dosage, have good taste and are stable during storage.
Inventors: |
Toba, Yasuhiro; (Tokyo,
JP) ; Takada, Yukihiro; (Kawagoe-shi, JP) ;
Morita, Yoshikazu; (Kawagoe-shi, JP) ; Abe,
Takumi; (Kawagoe-shi, JP) ; Kawakami, Hiroshi;
(Kawagoe-shi, JP) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE
CA
91614
US
|
Family ID: |
26607795 |
Appl. No.: |
10/050459 |
Filed: |
January 15, 2002 |
Current U.S.
Class: |
424/535 ;
435/68.1; 514/15.7; 514/7.4 |
Current CPC
Class: |
A23L 33/19 20160801;
A23V 2002/00 20130101; A61P 9/12 20180101; A61K 38/1709 20130101;
A23V 2002/00 20130101; A21D 2/268 20130101; A23V 2250/5424
20130101; A23V 2250/5488 20130101; A23V 2250/5424 20130101; A23V
2250/032 20130101; A23V 2250/61 20130101; A23V 2250/156 20130101;
A21D 2/263 20130101; A23L 2/66 20130101; A23V 2002/00 20130101;
A61K 35/20 20130101; A23J 1/20 20130101 |
Class at
Publication: |
514/12 ;
435/68.1 |
International
Class: |
A61K 038/17; C12P
021/06 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 16, 2001 |
JP |
2001-8189 |
Jan 16, 2001 |
JP |
2001-8190 |
Claims
What is claimed is:
1. A composition for improving lipid metabolism and/or reducing
high blood pressure comprising a milk-derived basic protein
fraction as an effective component and a suitable carrier for oral
administration.
2. A composition for improving lipid metabolism and/or reducing
high blood pressure according to claim 1 wherein said milk-derived
basic protein fraction contains about 15% or more by weight basic
amino acids in its amino acid composition.
3. A composition for improving lipid metabolism and/or reducing
high blood pressure according to claim 2 wherein said milk-derived
basic protein fraction comprises proteins having a molecular weight
ranging from about 3,000 to about 80,000.
4. A composition for improving lipid metabolism and/or reducing
high blood pressure according to claim 2 wherein said milk-derived
basic protein fraction contains more than about 95% by weight
protein.
5. A composition for improving lipid metabolism and/or reducing
high blood pressure according to claim 2 wherein said milk-derived
basic protein fraction contains less than about 5% by weight fat
and ash.
6. A composition for improving lipid metabolism and/or reducing
high blood pressure according to claim 1 wherein the milk-derived
basic protein fraction is a fraction obtained by ringing milk or a
milk-derived material into contact with cation exchange resins to
adsorb basic proteins and eluting a fraction adsorbed on the resins
with an eluent having a salt concentration of about 0.1 M to about
1.0 M.
7. A composition for improving lipid metabolism and/or reducing
high blood pressure comprising a basic peptide fraction which is
obtained by digesting a milk-derived basic protein fraction with a
protease as an effective component and a suitable carrier for oral
administration.
8. A composition for improving lipid metabolism and/or reducing
high blood pressure according to claim 7 wherein said protease is
at least one of proteases selected from the group consisting of
pepsin, trypsin, chymotrypsin, and pancreatin.
9. A drink for improving lipid metabolism and/or reducing high
blood pressure comprising the composition of claim 1.
10. A food product for improving lipid metabolism and/or reducing
high blood pressure comprising the composition of claim 1.
11. A tablet for improving lipid metabolism and/or reducing high
blood pressure comprising the composition of claim 1.
12. A drink for improving lipid metabolism and/or reducing high
blood pressure comprising the composition of claim 7.
13. A food product for improving lipid metabolism and/or reducing
high blood pressure comprising the composition of claim 7.
14. A tablet for improving lipid metabolism and/or reducing high
blood pressure comprising the composition of claim 7.
15. A method of improving lipid metabolism and/or reducing high
blood pressure comprising administering an effective amount of a
milk-derived basic protein fraction to a candidate for the
treatment or a patient in need thereof.
16. A method of improving lipid metabolism and/or reducing high
blood pressure according to claim 15, comprising orally
administering about 20 mg or more of the milk-derived basic protein
fraction per day.
17. A method of improving lipid metabolism and/or reducing high
blood pressure comprising administering an effective amount of a
basic peptide fraction which is obtained by digesting a
milk-derived basic protein fraction with a protease to a candidate
for the treatment or a patient in need thereof.
18. A method of improving lipid metabolism and/or reducing high
blood pressure according to claim 17, comprising orally
administering about 20 mg or more of the basic peptide fraction per
day.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to agents, drinks and food
products for improving lipid metabolism and reducing high blood
pressure and the combination thereof that are effective in treating
and preventing diseases such as fatty liver, hyperlipidemia,
arteriosclerosis, obesity and hypertension.
[0003] 2. Description of the Related Art
[0004] Lipid metabolism refers to catabolic (decomposing) and
anabolic (accumulating) processes of lipids, mainly comprising
triglicerides derived from food. Lipid metabolism generally
includes energy-releasing reaction of lipids, biosynthesis of fatty
acids, biosynthesis of acylglycerols, phospholipid metabolism,
cholesterol metabolism, and the like ("Biochemistry for Nutrition"
by Akira Misaki, Asakura Shoten, 1993, pp. 123-134).
[0005] In recent years, the mortality rate from cardiovascular
disease has been rapidly increasing and the correlation between the
risk of getting cardiovascular disease and the blood cholesterol
concentration has been pointed out. Meantime, several attempts have
been made to reduce the blood cholesterol concentration by using
food materials, which can be ingested in daily life. For example,
soybean protein (Arteriosclerosis 1988 72:115), whey protein (Agric
Biol Chem 1991 55:813; Japanese Patent Application Laid-open No.
H5-176713), soybean protein hydrolyzates (J Nutr 1990 120:977), and
egg yolk phospholipid (Agric Biol Chem 1989 53:2469) have been
tried. Further, a method making use of lactoalbumin, collagen,
soybean protein or wheat gluten and soybean lecithin in combination
(Nutr Rep Int 1983 28:621) and a method making use of tissue-like
soybean protein containing soybean lecithin (Ann Nutr Metab 1985
29:348), and the like have been proposed.
[0006] High blood pressure refers to essential hypertension,
etiology of which is unknown, and secondary hypertension, which is
associated with disease of the kidney, adrenal gland or nervous
system. In recent years, 90% of cases are reported to be essential
hypertension. Today, antihypertensive agents are frequently used
for the prevention and treatment of essential hypertension.
However, every conventional antihypertensive agent has a
disadvantage to show a certain adverse effect. For example,
individual drugs show characteristic adverse effects:
antihypertensive diuretics cause hypokaliemia or acidemia,
antihypertensive peripheral vasodilators cause hypoglobulia,
.beta.-blockers cause bronchoasthma, and .alpha.-methyldopa
increases glutamic-oxaloacetic transaminase (GOT) or
glutamic-pyruvic transaminase (GPT) values in the blood and causes
hemolytic anemia. Accordingly, a special consideration is required
in administering these antihypertensive agents, and the dosage and
period of administration for these agents are naturally
restricted.
[0007] Under the abovementioned circumstances, development of
antihypertensive agents without adverse effects has been strongly
urged, and antihypertensive agents having a microorganism-derived
substance as an effective component have drawn attention. Such
substances comprise, for example, high molecular weight
polysaccharides derived from lactic acid bacteria as an effective
component (Japanese Patent Application Laid-open No. S59-190929),
glycoproteins having a molecular weight of more than 10,000
isolated from chlorella algae (Japanese Patent Application
Laid-open No. S60-45603), viable or dead cells of bacteria of genus
Streptococcus (Japanese Patent Application Laid-open S61-221124),
dried beer yeast as an effective component (Japanese Patent
Application Laid-open No. S63-255234), or a hot water extract of
lactic acid bacteria (Japanese Patent Application Laid-open
S63-139129; Japanese Patent Application Laid-open No. H2-247127).
However, many of these substances are water insoluble and have
unpleasant taste, which prevent them from practical use.
[0008] Therefore, attempts have been made to develop
antihypertensive agents comprising substances contained in food
materials, which can be administered orally in daily life, as an
effective component. For example, an enzyme-digested casein product
(Food Develop 1997 32:37-39), and an enzyme-digested fish meat
product (Health Nutr Food Res 1998 1:62-71; Food Develop 1996
31:50-52) have been reported.
[0009] However, the methods described above have problems such that
a relatively large amount of ingestion is required, that flavor is
not desirable, and that precipitation occurs during storage when
made into drinks interfering with stable storage.
[0010] More importantly, no substance which can improves lipid
metabolism and reduce high blood pressure simultaneously is known.
A problem in lipid metabolism can be a cause of raising blood
pressure, and in that case, inadequate lipid metabolism is
associated with high blood pressure. For example, in some cases,
high blood cholesterol levels tend to cause arteriosclerosis which
leads to high blood pressure. Thus, if a substance which can both
improve lipid metabolism and reduce high blood pressure is
developed, the problem in both lipid metabolism and blood pressure
can effectively be resolved.
SUMMARY OF THE INVENTION
[0011] The present inventors found that a milk-derived basic
protein fraction or a basic peptide fraction, which is obtained by
digesting said basic protein fraction with a protease, e.g. pepsin
and pancreatin, can improve lipid metabolism and reduce high blood
pressure when administered orally. Further, the inventors found
that these basic protein fraction and basic peptide fraction can be
effectively used as an effective component for agents and drinks or
food products for improving lipid metabolism and high blood
pressure and the combination thereof.
[0012] In one embodiment an agent for improving lipid metabolism is
provided comprising a milk-derived basic protein fraction as an
effective component and a suitable carrier (e.g., for oral
administration). Preferably, this milk-derived basic protein
fraction contains 15% or more by weight basic amino acids in its
amino acid composition. Preferably, the milk-derived basic protein
fraction is obtained by bringing milk or a milk-derived material
into contact with cation exchange resins to adsorb basic proteins
and eluting a fraction adsorbed on the resins with an eluent having
a salt concentration of about 0.1 M to about 1.0 M.
[0013] In another embodiment an agent for improving lipid
metabolism is provided comprising a basic peptide fraction as an
effective component which is obtained by digesting the milk-derived
basic protein fraction by a protease. Preferably, the milk-derived
basic protein fraction is digested by at least one of proteases
selected from the group consisting of pepsin, trypsin,
chymotrypsin, and pancreatin.
[0014] In another embodiment a drink or food product for improving
lipid metabolism is provided to which the milk-derived basic
protein fraction or basic peptide fraction of the present invention
is admixed.
[0015] In another embodiment an agent for reducing high blood
pressure is provided comprising a milk-derived basic protein
fraction as an effective component and a suitable carrier (e.g.,
for oral administration). Preferably, this milk-derived basic
protein fraction contains 15% or more by weight basic amino acids
in its amino acid composition. Preferably, the milk-derived basic
protein fraction is obtained by bringing milk or a milk-derived
material into contact with cation exchange resins to adsorb basic
proteins and eluting a fraction adsorbed on the resins with an
eluent having a salt concentration of about 0.1 M to about 1.0
M.
[0016] In another embodiment an agent for reducing high blood
pressure is provided comprising a basic peptide fraction as an
effective component which is obtained by digesting the milk-derived
basic protein fraction by a protease. Preferably the milk-derived
basic protein fraction is digested by at least one of proteases
selected from the group consisting of pepsin, trypsin,
chymotrypsin, and pancreatin.
[0017] In another embodiment a drink or food product for reducing
high blood pressure is provided to which the milk-derived basic
protein fraction or basic peptide fraction of the present invention
is admixed.
[0018] An agent for improving lipid metabolism and an agent for
reducing high blood pressure can include basically the same
component. By examining activities and effects on each lipid
metabolism and blood pressure with respect to the content of the
component and other supplemental ingredients, desired balance
therebetween can readily be achieved. Agents for improving lipid
metabolism and/or reducing high blood pressure of the present
invention can be administered not only to a patient having the
symptoms but also to a candidate for the treatment of preventing
these symptoms.
[0019] For purposes of summarizing the invention and the advantages
achieved over the prior art, certain objects and advantages of the
invention have been described above. Of course, it is to be
understood that not necessarily all such objects or advantages may
be achieved in accordance with any particular embodiment of the
invention. Thus, for example, those skilled in the art will
recognize that the invention may be embodied or carried out in a
manner that achieves or optimizes one advantage or group of
advantages as taught herein without necessarily achieving other
objects or advantages as may be taught or suggested herein. Further
aspects, features and advantages of this invention will become
apparent from the detailed description of the preferred embodiments
which follow.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0020] Agents for improving lipid metabolism and reducing high
blood pressure and a combination thereof are characterized in that
they contain a milk-derived basic protein fraction or a basic
peptide fraction as an effective component. Said milk-derived basic
protein fraction can be obtained from mammalian milk such as cow
milk, human milk, goat milk, and ewe milk. The basic peptide
fraction can be obtained by digesting the milk-derived basic milk
fraction of the present invention with a protease.
[0021] In an embodiment, this milk-derived basic protein fraction
has the following characteristics as described hereinafter in Test
Examples 1 through 3. The present invention is not limited to this
embodiment.
[0022] 1) It comprises various proteins having a molecular weight
ranging from about 2,000 to about 80,000, preferably from about
3,000 to about 24,000, according to sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE). It has an
isoelectric point ranging from about 7.5 to about 11, preferably
from about 8 to about 10.
[0023] 2) It contains more than about 95% by weight protein and
small amounts of fat and ash.
[0024] 3) Proteins contained are mainly lactoferrin and
lactoperoxidase.
[0025] 4) As for the amino acid composition of proteins, it
contains more than about 15% by weight basic amino acids such as
lysine, histidine and arginine.
[0026] Such a basic protein fraction can be obtained, for example,
by bringing a milk material, such as skimmed milk and whey, into
contact with cation exchange resins to adsorb basic proteins,
eluting a basic protein fraction adsorbed on these resins with an
eluent having a salt concentration of about 0.1 M to about 1.0 M,
recovering this eluate fraction, desalting and concentrating this
fraction with a reverse osmotic (RO) membrane or by the
electrodialysis (ED) method, and drying the resulting fraction, if
necessary.
[0027] Further, a milk-derived basic protein fraction can be
obtained, for example, by a method in which milk or milk-derived
material is brought into contact with cation exchanger to adsorb
basic proteins, and then a basic protein fraction adsorbed on this
cation exchanger is eluted with an eluent having a pH higher than 5
and an ionic strength greater than 0.5 (Japanese Patent Application
Laid-open No. H5-202098), a method in which alginic acid gel is
used (Japanese Patent Application Laid-open No. S61-246198), a
method in which the fraction is obtained from whey using inorganic
porous particles (Japanese Patent Application Laid-open No.
H1-86839), and a method in which the fraction is obtained from milk
using a sulfate ester compound (Japanese Patent Application
Laid-open No. S63-255300). In the present invention, a basic
protein fraction obtained by any of such a method can be used. The
disclosure of the above references is herein incorporated by
reference.
[0028] Further, a milk-derived basic peptide fraction has the same
amino acid composition as the basic protein fraction. For example,
the milk-derived basic protein fraction obtained by any of the
abovementioned methods is treated with protease such as pepsin,
trypsin, and chymotrypsin, and if necessary further with protease
such as pancreatin, to obtain a peptide composition having an
average molecular weight of less than about 4,000, preferably from
about 1,000 to about 3,000.
[0029] In administering agents of the present invention for
improving lipid metabolism and reducing high blood pressure and the
combination thereof, a milk-derived basic protein fraction or the
basic peptide fraction as an effective component can be used
without further processing. Also, the milk-derived basic protein
and basic peptide fractions of the present invention can be
formulated into powders, granules, tablets, capsules, drinks, or
the like according to conventional methods. Further, these basic
protein fraction and basic peptide fraction, without further
processing or after formulation, can be admixed with nutrients,
drinks or food products to improve lipid metabolism and reduce high
blood pressure. An increased activity for improving lipid
metabolism and reducing high blood pressure and the combination
thereof can be expected by admixing the basic protein fraction or
the basic peptide fraction of the present invention along with
other components which are considered to have an activity to
improve lipid metabolism (e.g., 50 to 50,000% by weight with
respect to the basic protein fraction or the basic peptide
fraction), such as soybean protein, whey protein, soybean lecithin,
diacylglycerol, and soybean isoflavone, as well as the other
components which are considered to have an antihypertensive
activity (e.g., 100 to 50,000% by weight with respect to the basic
protein fraction or the basic peptide fraction), such as calcium,
magnesium, potassium, and dietary fiber. For example, 10 g of
soybean protein and 40 mg of soybean isoflavone can be used with 20
to 100 mg of the milk-derived basic protein fraction. In other
examples, 10 g of dietary fiber and 100 mg of magnesium can be used
with 20 to 100 mg of the milk-derived basic protein fraction. By
adjusting the amounts of the above supplemental components, an
activity of improving lipid metabolism and an activity of lowering
blood pressure can effectively be balanced. Further, materials
containing the milk-derived basic protein fraction or basic peptide
fraction of the present invention can be sterilized by heating
under ordinary conditions known to a skilled artisan (for example,
at 90.degree. C. for 10 min., at 121.degree. C. for 2 sec.) since
the milk-derived basic protein fraction and basic peptide fraction
of the present invention are relatively heat-stable.
[0030] For the purpose of this invention the "effective component"
means causing a result, such as the improvement of lipid
metabolism, reduction of high blood pressure, or both.
[0031] The dosage of agents for improving lipid metabolism and
reducing high blood pressure and the combination thereof according
to the present invention varies depending on age, therapeutic
effect and pathologic conditions. However, results of animal
experiments using rats revealed that an administration of 20 mg or
more of a basic protein fraction or basic peptide fraction per kg
body weight of rat was necessary to improve lipid metabolism and
high blood pressure. Therefore, according to an extrapolation
method (A Sequel to Medicinal Development, 1993 8:7-18), an
effective daily dose for a human adult is estimated to be about 20
mg or more, preferably from about 20 to about 1000 mg, more
preferably from about 40 to about 100 mg. Accordingly, the
fractions can be admixed with drinks or food products or
administered as a medicine so as to securely attain this dosage
(for example, 2 m % to 2% in a drink or food product, 0.2% to 20%
in a medicine).
[0032] The present invention is described in but is not limited to
the following examples and test examples.
EXAMPLE 1
[0033] A column (5 cm in diameter and 30 cm in height) filled with
cation exchange resins, sulfonated Chitopearl (400 g; a product of
Fuji Boseki Co., Ltd.), was thoroughly washed with deionized water.
Skimmed milk (40 L, pH 6.7) was passed through the column at a flow
rate of 25 ml/min, after which the column was thoroughly washed
with deionized water, and then a fraction of basic proteins
adsorbed on the resins was eluted with a 0.02 M carbonic acid
buffer solution (pH 7.0) containing 0.98 M sodium chloride. The
resulting eluate was desalted and concentrated using a reverse
osmotic (RO) membrane and then freeze-dried to obtain 21 g of a
powdered basic protein fraction.
Test Example 1
[0034] The basic protein fraction obtained in Example 1 was
subjected to sodium dodecyl sulfate polyacrylamide gel
electrophoresis (SDS-PAGE), which revealed that the molecular
weights of the proteins ranged from about 3,000 to about
80,000.
Test Example 2
[0035] The composition of the basic protein fraction obtained in
Example 1 was analyzed. Results are shown in Table 1. As shown in
Table 1, protein is the major component of this fraction.
1 TABLE 1 Unit: % by weight Water 1.06 Protein 96.5 Fat 0.56 Ash
0.27 Others 1.61
Test Example 3
[0036] The amino acid composition of the basic protein fraction
obtained in Example 1 was analyzed using an amino acid analyzer
(Model L-8500, a product of Hitachi Ltd.) after hydrolysis with 6 N
hydrochloric acid at 110.degree. C. for 24 hours. Results are shown
in Table 2. This basic protein fraction contains more than 15% by
weight basic amino acids (lysine, histidine and arginine) in its
amino acid composition.
2 TABLE 2 Unit: % by weight Aspartic acid 10.1 Serine 5.3 Glutamic
acid 12.3 Proline 4.7 Alanine 5.7 Leucine 10.2 Lysine 8.4 Histidine
2.5 Arginine 7.2 Others 33.6
EXAMPLE 2
[0037] A column (100 cm in diameter and 10 cm in height) filled
with cation exchange resins, SP Toyopearl (30 kg; a product of
Toso), was thoroughly washed with deionized water. Cheese whey (30
t, pH 6.2) which was sterilized by heating at 121.degree. C. for 30
seconds was passed through the column at a flow rate of 10 L/min,
after which the column was thoroughly washed with deionized water,
and then a fraction of basic proteins adsorbed on the resins was
eluted with a 0.1 M citric acid buffer solution (pH 5.7) containing
0.9 M sodium chloride. The resulting eluate was desalted and
concentrated by an electrodialysis (ED) method and then
freeze-dried to obtain 183 g of a powdered basic protein
fraction.
EXAMPLE 3
[0038] The basic protein fraction powder obtained in Example 1 (50
g) was dissolved in 10 L of distilled water, 50 ml of a 1% by
weight solution of pancreatin (a product of Sigma) was added, and
reaction was carried out at 37.degree. C. for 2 hours. To stop the
reaction, the enzyme was inactivated by heating at 80.degree. C.
for 10 minutes, after which the reaction solution was concentrated
and freeze-dried to obtain 48.3 g of a powdered basic peptide
fraction.
Test Example 4
[0039] For the powdered basic protein fraction obtained in Example
1 and the powdered basic peptide fraction obtained in Example 3, an
activity to improve lipid metabolism was examined by an animal
experiment using Wistar male rats (4 weeks of age). The rats were
divided into 5 experimental groups (N=8): a group to which
physiological saline was administered (group A), a group to which
20 mg of the powdered basic protein fraction per kg body weight of
rat were administered (group B), a group to which 200 mg of the
powdered basic protein fraction per kg body weight of rat were
administered (group C), a group to which 20 mg of the powdered
basic peptide fraction per kg body weight of rat were administered
(group D), a group to which 200 mg of the powdered basic peptide
fraction per kg body weight of rat were administered (group E). The
administration was carried out using a gavage once a day for 10
weeks. During this 10-week period, animals were fed feed containing
1% by weight cholesterol and 0.25% by weight sodium cholate.
[0040] Following the 10 weeks of administration of the powdered
basic protein fraction or powered basic peptide fraction, the total
cholesterol, high-density lipoprotein cholesterol, low-density and
very low-density lipoprotein cholesterols, and neutral fat in the
serum were measured. Results are shown in Table 3.
3TABLE 3 (Unit: mg/dl) Group A Group B Group C Group D Group E
Tchol 145 .+-. 13.sup.a 112 .+-. 15.sup.b 90 .+-. 16.sup.b,c 109
.+-. 16.sup.b,c 88 .+-. 18.sup.c HDL 37 .+-. 9 35 .+-. 6 44 .+-. 10
37 .+-. 9 45 .+-. 7 LDL + VLDL 108 .+-. 8.sup.a 77 .+-. 13.sup.b 47
.+-. 10.sup.c 72 .+-. 14.sup.b 43 .+-. 12.sup.c TG 194 .+-.
19.sup.a 173 .+-. 18.sup.a 136 .+-. 22.sup.b 169 .+-. 27.sup.a,b
136 .+-. 32.sup.b TChol: total cholesterol; HDL: high-density
lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol;
VLDL: very low-density lipoprotein cholesterol; TG: neutral fat.
Superscripts in Table 3 show significant difference between
different groups (p < 0.05).
[0041] The results showed that in all experimental groups, i.e.,
group B, group C, group D and group E the total cholesterol was
significantly lower compared to the control group, i.e., group A.
In detail, the figures for the low-density and very low-density
lipoprotein cholesterols, which are considered to be bad
cholesterols, were significantly lower in group B, group C, group
D, and group E as compared to group A while the figures for the
high-density lipoprotein, which is considered to be good
cholesterol, were not significantly different between the groups.
Figures for the neutral fat were significantly lower in group C and
group E as compared to group A.
[0042] These results revealed that the basic protein fraction and
the basic peptide fraction have an activity to lower the levels of
serum cholesterols, particularly the low-density and very
low-density cholesterols, which are considered to be bad
cholesterols, and the levels of serum neutral fat, thereby
improving lipid metabolism.
[0043] Further, it was revealed that the activity to improve lipid
metabolism was observed when at least 20 mg per kg rat body weight
of the basic protein fraction or the basic peptide fraction were
administered.
Test Example 5
[0044] For the powdered basic protein fraction obtained in Example
1 and the powdered basic peptide fraction obtained in Example 3, an
activity to lower blood pressure was examined in vivo using SHR
rats which had a congenital hypertensive genetic factor. SHR male
rats (4 weeks old) were divided into 5 experimental groups (N=8): a
group to which physiological saline was administered (group A), a
group to which 20 mg of the powdered basic protein fraction per kg
body weight of rat were administered (group B), a group to which
200 mg of the powdered basic protein fraction per kg body weight of
rat were administered (group C), a group to which 20 mg of the
powdered basic peptide fraction per kg body weight of rat were
administered (group D), a group to which 200 mg of the powdered
basic peptide fraction per kg body weight of rat were administered
(group E). The administration was carried out using a gavage once a
day for 8 weeks. After 4 weeks and 8 weeks, systolic blood pressure
was measured. Results are shown in Table 4.
4TABLE 4 (Unit: mm Hg) Group A Group B Group C Group D Group E
After 4 238 .+-. 15.sup.a 226 .+-. 13.sup.a,b 221 .+-. 11.sup.b 231
.+-. 8.sup.a,b 217 .+-. 13.sup.b weeks After 8 242 .+-. 13.sup.a
221 .+-. 9.sup.b 212 .+-. 7.sup.b 222 .+-. 10.sup.b 214 .+-.
18.sup.b weeks Superscripts in Table 4 show significant difference
between different groups (p < 0.05).
[0045] The results showed that after 4 weeks, experimental groups,
C and E showed significantly lower systolic blood pressure compared
to the control group, i.e., group A. Further, the systolic blood
pressure after 8 weeks was significantly lower in group B, group C,
group D, and group E compared to group A.
[0046] These results revealed that the basic protein fraction and
the basic peptide fraction have an antihypertensive activity.
[0047] Further, it was revealed that the antihypertensive activity
was observed when at least 20 mg per kg rat body weight of the
basic protein fraction or the basic peptide fraction were
administered.
EXAMPLE 4
[0048] A drink for improving lipid metabolism and reducing high
blood pressure having the composition shown in Table 5 was
produced. The taste of the resulting drink was good and did not
deteriorate during storage for one year at room temperature,
without precipitation or the like.
5 TABLE 5 Mixed isomerized sugars 15 Fruit juice 10 Citric acid 0.5
Basic protein fraction powder (Example 1) 0.1 Flavoring 0.1 Mineral
0.1 Water 74.2 (Unit: % by weight)
EXAMPLE 5
[0049] Dough having the composition shown in Table 6 was prepared,
molded and baked to produce biscuits for improving lipid
metabolism.
6 TABLE 6 Flour 50 Sugar 20 Table salt 0.5 Margarine 12.5 Egg 11.5
Water 2.5 Mineral mixture 0.8 Basic protein fraction powder
(Example 2) 1.2 Soybean isoflavone 1 (Unit: % by weight)
[0050] Dough having the composition shown in Table 7 was prepared,
molded and baked to produce antihypertensive biscuits.
7 TABLE 7 Flour 50 Sugar 20 Table salt 0.5 Margarine 12.5 Egg 12.5
Water 2.5 Mineral mixture 0.8 Basic protein fraction powder
(Example 2) 1.2 (Unit: % by weight)
EXAMPLE 6
[0051] Tablets for improving lipid metabolism having the
composition shown in Table 8 were produced.
8 TABLE 8 Hydrous crystalline glucose 73.5 Soybean protein 10 Basic
protein fraction powder (Example 2) 10 Mineral mixture 5 Sugar
esters 1 Flavoring 0.5 (Unit: % by weight)
[0052] Antihypertensive tablets having the composition shown in
Table 9 were produced.
9 TABLE 9 Hydrous crystalline glucose 83.5 Basic protein fraction
powder (Example 2) 10 Mineral mixture 5 Sugar esters 1 Flavoring
0.5 (Unit: % by weight)
[0053] Since the agents, drinks and food products for improving
lipid metabolism and reducing high blood pressure of the present
invention can improve lipid metabolism and reduce high blood
pressure through ingestion, they are effective in treating and
preventing diseases such as fatty liver, hyperlipidemia,
arteriosclerosis, obesity, and hypertension.
[0054] While the present invention has been described in some
detail for purposes of clarity and understanding, one skilled in
the art will appreciate that various changes in form and detail can
be made without departing from the true scope of the invention. All
patents, patent applications and publications referred to above are
hereby incorporated by reference. Further, this application claims
priority to Japanese Patent Application No. 2001-008189 and No.
2001-008190, both filed Jan. 16, 2001, and the disclosure of which
is herein incorporated by reference in its entirety.
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