U.S. patent application number 10/551765 was filed with the patent office on 2006-12-07 for lipid-regulating agent and use thereof.
Invention is credited to Shigeharu Fukuda, Michio Kubota, Toshio Miyake, Kazuyuki Oku.
Application Number | 20060276432 10/551765 |
Document ID | / |
Family ID | 33156723 |
Filed Date | 2006-12-07 |
United States Patent
Application |
20060276432 |
Kind Code |
A1 |
Oku; Kazuyuki ; et
al. |
December 7, 2006 |
Lipid-regulating agent and use thereof
Abstract
The object of the present invention is to provide a
lipid-regulating agent or a composition for regulating the amount
of lipids comprising the agent. The present invention solves the
above object by providing a lipid-regulating agent comprising a
cyclic tetrasaccharide and/or its saccharide-derivative(s) and a
composition for regulating the amount of lipids comprising the
lipid-regulating agent.
Inventors: |
Oku; Kazuyuki; (Okayama,
JP) ; Kubota; Michio; (Okayama, JP) ; Fukuda;
Shigeharu; (Okayama, JP) ; Miyake; Toshio;
(Okayama, JP) |
Correspondence
Address: |
BROWDY AND NEIMARK, P.L.L.C.;624 NINTH STREET, NW
SUITE 300
WASHINGTON
DC
20001-5303
US
|
Family ID: |
33156723 |
Appl. No.: |
10/551765 |
Filed: |
March 24, 2004 |
PCT Filed: |
March 24, 2004 |
PCT NO: |
PCT/JP04/04079 |
371 Date: |
October 3, 2005 |
Current U.S.
Class: |
514/61 ; 514/27;
514/456 |
Current CPC
Class: |
A61P 9/00 20180101; A61P
9/04 20180101; A23D 9/007 20130101; A61P 1/00 20180101; A61P 3/04
20180101; A61P 3/10 20180101; A61P 3/06 20180101; A61P 1/10
20180101; A61P 9/12 20180101; A61P 9/10 20180101; A61P 7/02
20180101; A61P 1/16 20180101; A23K 20/163 20160501; C07H 3/06
20130101; A61P 35/00 20180101; A61K 31/702 20130101; A23L 33/10
20160801 |
Class at
Publication: |
514/061 ;
514/027; 514/456 |
International
Class: |
A61K 31/724 20060101
A61K031/724; A61K 31/7048 20060101 A61K031/7048; A61K 31/353
20060101 A61K031/353 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 3, 2003 |
JP |
2003-100408 |
Claims
1. A lipid-regulating agent, which comprises a cyclic
tetrasaccharide, represented by the formula of cyclo {{cube
root}6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosyl-(1-
.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosyl--
(1.fwdarw.}, and/or its saccharide-derivative(s) as an effective
ingredient(s)
2. The lipid-regulating agent of claim 1, where one or more
substances selected from the group consisting of a non-reducing
saccharide, reducing saccharide, cyclodextrin, water-soluble
polysaccharide, polyphenol, spice, acidifier, seasoning, alcohol,
organic acid, organic acid salt, inorganic salt, emulsifier,
flavor, and coloring are incorporated into said cyclic
tetrasaccharide, represented by the formula of cyclo
{.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosy-
l-(1.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyrano-
syl-(.fwdarw.}, and/or said saccharide-derivative(s)
3. The lipid-regulating agent of claim 2, wherein said non-reducing
saccharide is one or more saccharides selected from the group
consisting of maltitol, .alpha.,.alpha.-trehalose, and a
saccharide-derivative of .alpha.,.alpha.-trehalose.
4. The lipid-regulating agent of claim 2, wherein said polyphenol
is one or more substances selected from the group consisting of
flavonoids such as hesperetin, naringenin, querucetin, hesperidin,
enzymatically-modified hesperidin, naringin, enzymatically-modified
naringin, rutin, enzymatically-modified rutin, and
proanthocyanidin; and catechins such as catechin and
epigallocatechin.
5. The lipid-regulating agent of claim 1, which comprises said
cyclic tetrasaccharide, represented by the formula of cyclo
{.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosy-
l-(1.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyrano-
syl-(1.fwdarw.}, and/or said saccharide-derivative(s) in a total
amount of 0.1% (w/w) or higher, on a dry solid basis.
6. A composition for regulating the amount of lipids, which
comprises the lipid-regulating agent of claim 1.
7. The composition for regulating the amount of lipids of claim 6,
which comprises a cyclic tetrasaccharide, represented by the
formula of cyclo
{.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosy-
l-(1.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyrano-
syl-(1.fwdarw.}, and/or said saccharide-derivative(s) in a total
amount of 0.01% (w/w) or higher, on a dry solid basis.
8. The lipid-regulating agent claim 1, where lipid-regulating means
the regulation the amount of lipids in said living body.
9. The lipid-regulating agent of claim 8, wherein said lipid in
said living body is one or more lipids selected from the group
consisting of free fatty acids, simple lipids (homolipids),
compound lipids (heterolipids), lipoproteins, and free
cholesterols.
10. The lipid-regulating agent of claim 8, wherein said lipids in
said living body exist in one or more tissues or organs selected
from the group consisting of blood, subcutaneous tissue,
intracutaneous tissue, testis, kidney, heart, liver, and digestive
tract.
11. The lipid-regulating agent of claim 9, wherein said simple
lipids (homolipids) are triglycerides.
12. The lipid-regulating agent of claim 1, which is used for
improving a lifestyle-related disease.
13. The lipid-regulating agent of claim 12, wherein said
lifestyle-related disease is one or more diseases selected from the
group consisting of hyperlipemia, arteriosclerosis, angiostenosis,
vascular blockage, hypertension, thrombosis, angina, cardiac
infarction, cardiac incompetence, brain infarction, fatty
incompetence, brain infarction, fatty liver, cirrhosis, adiposis,
constipation, colon cancer, and diabetes.
14. The lipid-regulating agent of claim 1, which is used for one or
more objects of inhibiting the increase of weight, decreasing total
cholesterol, decreasing LDL-cholesterol, regulating the metabolism
of lipoproteins, inhibiting the accumulation of lipids, regulating
the metabolism of bile acids, and improving the intestinal
function.
15. The lipid-regulating agent of claim 1, which is in the form of
a pharmaceutical, medicated cosmetic, healthy food, food and
beverage, feed, or bait.
16. The lipid-regulating agent of claim 1, which is used for the
substitution of lipids.
Description
TECHNICAL FIELD
[0001] The present invention relates to a novel lipid-regulating
agent and use thereof, particularly, to a novel lipid-regulating
agent comprising a non-reducing saccharide where four glucose
molecules are bound via alternating .alpha.-1,3 and .alpha.-1,6
linkages, i.e., a cyclic tetrasaccharide, represented by the
formula of cyclo
{.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosy-
l-(1.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyrano-
syl-(1.fwdarw.) (hereinafter, simply abbreviated as "CTS" in this
specification), and/or its saccharide-derivative(s) as an effective
ingredient(s), and to a composition for regulating the amount of
lipids, comprising the lipid-regulating agent.
BACKGROUND ART
[0002] In recent years, accompanying with the progress in living
standard, dietary habits have altered to Western-style in many
countries including Japan. Therefore, we tend to intake excess
calories and lipids compared with a traditional dietary habit. As a
result, patients and potential patients of lifestyle-related
diseases such as hyperlipemia, cholesteremia, diabetes,
hypertension, adiposis, etc. have increased. Among those, adiposis,
which is caused by the excess increase of lipids in the living
body, is a risk factor of those lifestyle-related diseases and is
recognized as a large problem on human health. Furthermore,
adiposis is a risk factor of hyperlipemia, cholesteremia,
cardiovascular disease, hepatic disease, malignant tumor, diabetes,
etc. and is suggested to involve the crisis and the aggravation of
gout, cholecystolithiasis, etc.
[0003] Particularly, in Japanese society which is on the way of an
aging society, the prevention of adiposis is highlighted as an
important object from a viewpoint of preventive medicine because
adiposis is a risk factor of lifestyle-related diseases. Also,
women in and/or after adolescence tend to hate the corpulence. Some
of them get out of order of hormone valance and cause critical
diseases such as osteoporosis by the diet with wrong methods,
causing excess burden on the body.
[0004] Usually, a method for limiting calories by ingesting low-fat
or low-calorie foods and that for burning of f calories by aerobic
exercises are recommended as a means of curing or preventing
adiposis and hyperlipemia. However, many people are forced to
abandon such methods because they require pointed leadings and a
long period. Also, the dietary restriction is not preferable from
the viewpoint of mental health. Although taking drugs is effective
for curing or preventing adiposis and hyperlipemia, the side-effect
and cost of the drugs cause problems.
[0005] It is particularly desirable for patients and potential
patients of diseases such as adiposis, hyperlipemia, cholesteremia,
etc., to prevent such diseases effectively with taking delicious
and safe foods, snacks, and healthy foods in a daily eating habit.
Under these circumstances, the development of effective materials
for curing or preventing adiposis, hyperlipemia, cholesteremia,
diabetes, etc., which show delicious taste intact or in combination
of other foods, is now in progress. Recently, accompanying with the
recent health fad or the establishment of health-promoting foods
such as foods specified health use, general public rise awareness
for curing and preventing adiposis, hyperlipemia, cholesteremia,
diabetes, etc., by ingesting foods and beverages. Under these
circumstances, many food materials such as fats including
diacylglycerols and plant sterols, which inhibit uptake of fats and
cholesterols; and low-calorie sweeteners including synthetic
highly-sweetened sweeteners and sugar alcohols are already
commercialized. For example, lipid-reducing agents, comprising
saccharides such as xyloglucan, agarooligosaccharide, etc., as
effective ingredients, are disclosed in Japanese Patent Kokai Nos.
147,934/95, 224,608/97, and 349,485/99. Further, a
lipid-metabolism-improving agent, comprising substances such as
hesperetin, naringenin, etc., as effective ingredients, are
disclosed in Japanese Patent Kokai No. 280,358/96. Furthermore, in
"SHOKUMOTSU-SENI KISO-TO-OYO (Dietary fiber, its basis and
application)" published by ASAKURA-SHOTEN in 1997, it is disclosed
that dietary-fifers represented by cellulose or gummy substances
involve in the metabolism of lipids, bile acids, and cholesterols
and have an activity of improving lifestyle-related diseases.
However, in the case of using those ingredients for materials of
foods and beverages, some of those ingredients are food materials
having disadvantages of deteriorating the taste, flavor, and
mouthfeel; being not effective without taking in a relatively large
amount; or causing diarrhea depending on the physical condition or
the predisposition. To meet the recent diversified eating habit, it
is desirable to develop food materials having a safety and activity
of preventing or treating diseases such as adiposis, hyperlipemia,
cholesteremia, diabetes, etc., without causing the deterioration of
taste, flavor, and mouthfeel even when one takes it habitually.
[0006] While, the applicant of the present invention disclosed a
novel process for producing CTS and/or a saccharide composition
comprising CTS and its saccharide-derivative(s), and a composition
comprising those saccharides in International Publication Nos. WO
01/090,338, WO 02/010,361, and WO 02/072,594. Also, the applicant
of the present invention disclosed in those specifications that
those saccharides are hardly metabolized by intestinal bacteria and
have a dietary fiber-like activity. However, in all those
literatures, there is no disclosure about the lipid-regulating
activity of CTS and/or its saccharide-derivative(s) or a
composition comprising those saccharides.
DISCLOSURE OF INVENTION
[0007] The first object of the present invention is to provide a
lipid-regulating agent for preventing or improving the increase or
the accumulation of lipids, which is taken from foods and beverages
or synthesized in a living body, in blood or in tissues and organs
in a living body. The second object of the present invention is to
provide a composition for regulating the amount of lipids,
comprising the lipid-regulating agent.
[0008] To solve the above objects, the present inventors have
studied on a lipid-regulating agent comprising a saccharide as an
effective ingredient for a long period of time. As a result, the
present inventors found that CTS and/or its
saccharide-derivative(s) effected on the regulation of the amount
of lipids, and then inhibits the increase of body weight, and
regulates the amount of cholesterol to the ordinary level or very
close to it. The present inventors accomplished the present
invention by establishing a novel lipid-regulating agent and a
composition for regulating the amount of lipids, comprising the
lipid-regulating agent.
BEST MODE FOR CARRYING OUT THE INVENTION
[0009] The sacchride-derivative of CTS as referred to as in the
present invention means a sacchride where one or more glycosyl
residues are bound to CTS, and the glycosyl residues include one or
more kinds of glycosyl residue, for example, a saccharide where one
or more glucose molecules are bound to one or more hydroxyl groups
of CTS, which is obtained by allowing
.alpha.-isomaltosylglucosaccharide-forming enzyme and
.alpha.-isomaltosyl-transferring enzyme to act on starch. In
addition, such saccharides include those which one or more glycosyl
residues such as .alpha.-D-glucopyranosyl residue,
.beta.-D-galactopyranosyl residue, and .beta.-D-chitosaminyl
residue are transferred to one or more hydroxyl groups of CTS
and/or a saccharide-derivative of CTS described above. The
saccharide-derivatives of CTS are obtainable by allowing one or
more saccharide-transferring enzymes such as cyclomaltodextrin
glucanotransferase, .beta.-galactosidase, .alpha.-galactosidase,
lysozyme, etc., to act on their substrates such as monosaccharides,
oligosaccharides and/or polysaccharides in the presence of CTS
and/or its saccharide-derivative(s) according to the method
disclosed by the inventors of the present invention in
International Publication No. WO 02/072,594. Further, saccharides,
prepared by transferring one or more glycosyl residues such as
.alpha.-D-glucopyranosyl residue, .beta.-D-galactopyranosyl
residue, .beta.-D-chitosaminyl residue, etc., to glycosyl residues
including .alpha.-D-glucopyranosyl residue,
.beta.-D-galactopyranosyl residue, and/or .beta.-D-chitosaminyl
residue of saccharide-derivatives of CTS, can be arbitrarily
used.
[0010] CTS and its saccharide-derivatives usable in the present
invention are not restricted by their origins and processes, and
they can be produced by fermentation method, enzymatic method, and
organic synthesis. The reaction mixture obtainable by the above
methods can be used intact as CTS and its saccharide-derivatives,
or used as a solution thereof. The reaction mixture can be
partially or highly purified by using ion-exchange resins to remove
impurities. Also, mixtures of CTS and one or more
saccharide-derivatives of CTS can be arbitrarily used in the
present invention. CTS and its saccharide-derivatives can be
produced from amylaceous substances or saccharides inherent to the
enzymatic methods such as a method for converting panose into CTS
by .alpha.-isomaltosyl-transferring enzyme, disclosed by the same
applicant as the present invention in International Publication No.
WO 01/090,338, and a method for producing CTS from starch by using
.alpha.-isomaltosylglucosaccharide-forming enzyme and
.alpha.-ismaltosyl-transferring enzyme in combination, disclosed in
International Publication No. WO 02/010,361. CTS and its
saccharide-derivatives can be also produced by the method disclosed
by the same applicant as the present invention in International
Publication No. WO 02/072,594. These methods can be used for
producing CTS and its saccharide-derivatives in a high efficiency
and a lower cost using starch as an abundant and low cost material.
Therefore, CTS and its saccharide-derivatives can be advantageously
produced on an industrial scale. CTS has a form of anhydrous
amorphous, anhydrous crystalline, crystalline monohydrate, or
crystalline pentahydrate, and any of which can be used in the
present invention. Among these, CTS in an anhydrous crystalline,
crystalline monohydrate, or anhydrous amorphous form has a
satisfactory dehydrating activity and it can be used to powderize
or solidify hydrous substances as a dehydrating agent by admixing
with a hydrous substance such as unsaturated compounds. Therefore,
CTS in such a form can be advantageously used for producing a high
quality powder or solid product, comprising CTS as an effective
ingredient.
[0011] Lipids, which can be regulated by the lipid-regulating agent
of the present invention, include homolipids, heterolipids and
induced lipids in living bodies; concretely, homolipids such as
neutral fats including triglycerides; heterolipids such as
glycerophospholipids, glyceroglycolipids, sphingophospholipids, and
sphingoglycolipids; heterolipids such as lipoproteins including
high-density lipoprotein cholesterol (HDL-cholesterol), low-density
lipoprotein cholesterol (LDL-cholesterol), and remnant-like
lipoprotein cholesterol; and lipoproteins in cellular membrane;
induced lipids such as saturated fatty acids including stearic acid
and palmitic acid; unsaturated fatty acids including
.alpha.-linoleic acid and .alpha.-linolenic acid; and free fatty
acids including multiple unsaturated fatty acids, fatty alcohols,
steroids, and cholesterols. In this specification, the sum of
cholesterols, contained in serum lipoprotein, such as high-density
lipoprotein cholesterol, low-density lipoprotein cholesterol, and
remnant-like lipoprotein cholesterol, and free cholesterols in
blood may be called as "total cholesterol".
[0012] It is generally well known that lipids in a living body
increase in body fluids including blood and are accumulated as
subcutaneous fats or visceral fats in or around various visceral
organs such as testicle, kidney, heart, liver, gastrointestinal
tract, due to metabolic disorder or excess intake of foods. The
term "the regulation of lipids" as referred to as in the present
invention means inhibiting the accumulation of lipids in a living
body, reducing those lipids in a living body to a normal level, and
keeping them in the normal level. The term "the regulation of
lipids" also means reducing cholesterols and triglycerides
deposited to blood vessel wall as observed in the case of arterial
sclerosis.
[0013] The term "lifestyle-related diseases" as referred to as in
the present invention means chronic diseases caused by excess
accumulation of lipids, concretely, hyperlipemia, asteriosclerosis,
angiostenosis, vascular obstruction, hypertention, increase of
blood adhesiveness, formation of thrombus, angina, cardiac
infarction, cardiac incompetence, brain inferction, fatty liver,
cirrhosis, adiposis, constipation, malignant tumor such as hepatoma
and tumor of large intestine, diabetes, and various diseases
accompanied by the above diseases.
[0014] The lipid-regulating agent of the present invention can be
used for domestic animals including cattle, pig, etc.; poultry
including chicken, duck, etc.; cultivated fish and shellfish such
as bream, flatfish, young yellowtail, and clam; cultivated
crustacean such as shrimp, crab, etc.; insects including silkworm,
honeybee, etc.; and pets including dogs, cats, birds, etc., as well
as for humans. The lipid-regulating agent of the present invention
can be used for regulating the increase of lipids in living bodies
of animals including human, caused by excess intake of foods and
feeds and by congenital or acquired metabolic disorders. Further,
the lipid-regulating agent of the present invention can be
arbitrarily used for reducing lipids of animals even in the case of
the index value being in a normal range, as well as those in the
case of lifestyle-related disease such as adiposis, hyperlipemia,
cholesteremia, etc., being caused by the increase of lipids in a
living body.
[0015] The "corpulence" as referred to as in the present invention
means, in the case of human, one whose body mass index (BMI), a
value calculated by dividing two times one's weight (kg) by one's
body height (m), which is a criterion used in Japan Society for the
Study of Obesity, of higher than 25. Even in the case of being BMI
of 25 or lower, one whose amount of lipids of specific parts such
as tissues and visceral organs is higher than the normal level is
classified into "corpulence" in the present invention. For example,
one whose visceral fats are higher than the normal level is
classified into "corpulence". Visceral fats are recognized as a
risk factor of lifestyle-related diseases.
[0016] The term "hyperlipemia" as referred to as in the present
invention means the fettle that triglyceride and/or cholesterol
content(s) in the blood and/or body fluid is higher than the normal
level. In the case of human, "hyperlipemia" means one whose
triglyceride content in blood is higher than 150 mg/100 ml-blood.
Also, "hyperlipemia" includes "hypercholesterolemia". The term
"hypercholesterolemia" as referred to as in the present invention
means the fettle that total cholesterol content in the blood is 220
mg/100 ml-blood or higher. Also, "hypercholesterolemia" includes
fettles that the high-density lipoprotein (HDL) cholesterol content
in the blood is 41 mg/100 ml-blood or lower and that remnant-like
lipoprotein cholesterol content in the blood is 7.5 mg/100 ml-blood
or higher.
[0017] Since CTS and its saccharide-derivatives, effective
ingredients of the lipid-regulating agent of the present invention,
are stable and do not affect the flavors of foods and beverages,
the lipid-regulating agent of the present invention can be used
intact or in combination with one or more ingredients, having an
effect on lipid-metabolism in the living body, such as xyloglucan
and its hydrolyzates, galactooligosaccharide-sulfate obtainable by
hydrolyzing porphylan, hesperetin, naringenin, etc., disclosed in
Japanese Patent Kokai Nos. 147,934/95, 224,608/97, 349,485/99, and
280,358/96. Further, the lipid-regulating agent of the present
invention can be arbitrarily used freely in combination with
dietary fibers such as cellulose, pectin, pullulan, amylose, their
derivatives, and hemicellulose, disclosed in
"SHOKUMOTSU-SENIKISO-TO-OYO" (Dietaryfiber, its basis and
application) published by ASAKURA-SHOTEN in 1997. In addition to
those ingredients, one or more well-known ingredients which are
known to involve the metabolism and the regulation of lipids, such
as flavonoids including hesperidin, enzyme-treated hesperidin,
naringin, enzyme-treated naringin, rutin, enzyme-treatedrutin, and
proanthocyanidin; catechins including catechin, epicatechin, and
epigallocatechin; plant sterols including diacylglycerol,
polyenphosphatidylcholine; royal jelly, flavastatin sodium salt,
simbastatin, simfibrate, nicotinic acid, nicomol, clinofibrate,
clofibrate, pantethine, riboflavin butyrate, etc., can be
arbitrarily used with the lipid-regulating agent of the present
invention to enhance the lipid-regulating activity.
[0018] The lipid-regulating agent of the present invention,
comprising CTS and/or its saccharide-derivatives as effective
ingredients, can be arbitrarily used intact or by admixing with
fillers, excipients, binders, etc., to shape into various forms
such as granules, spheres, sticks, plates, cubes, tablets, etc.
[0019] The lipid-regulating agent, comprising CTS and its
saccharide-derivatives, of the present invention well harmonizes
with various substances having a taste such as sourness, salty
taste, astringency, delicious taste, bitterness, etc., and has a
satisfactory acid tolerance and thermal stability. Therefore, the
lipid-regulating agent can be advantageously used as a material for
general foods, medicated cosmetics, pharmaceuticals, feeds, and pet
foods. The products comprising the lipid-regulating agent can be
used similarly as those not comprising the agent. The products
comprising the lipid-regulating agent can be advantageously used as
foods and beverages, medicated cosmetics, pharmaceuticals, their
intermediates, and materials for patients of lifestyle-related
diseases, whose intake of calorie and lipids are restricted, for
the purpose of diet, the prevention of lifestyle-related diseases,
curing or preventing adiposis, diabetes, hyperlipemia, fatty liver,
etc. The lipid-regulating agent of the present invention can be
arbitrarily used for feeds, pet foods, etc., for the purpose of
preventing adiposis or improving hyperlipemia and fatty liver of
domestic animals, poultry, and pets.
[0020] The lipid-regulating agent of the present invention can be
used for producing various foods and beverages such as seasonings,
mixed seasonings, various Japanese or Western confectioneries,
breads, ice-creams, syrups, pastes, processed vegetables, pickles,
seasoning for pickles, meat products, marine products, delicacy,
side dishes, milk products, cooling beverages, various premixes,
instant foods, chilled foods, frozen foods, retort foods, dried
foods, baby foods, foods for curing, drinks, peptide foods, etc.
The lipid-regulating agent of the present invention can be used as
a substitute of a part or the whole of fats for producing foods and
beverages comprising fat. Foods and beverages with a creamy taste
and good texture can be produced by using the lipid-regulating
agent of the present invention even in the case of using low
amounts of fat. Such foods and beverages comprising fat include
brownie, pie filling, frozen dessert, salad dressing, spread, cake,
cookie, powdery beverage, etc., which are produced by using lard,
beef tallow, fish oil, vegetable oil, milk fat, butter, cheese,
shortening, margarine, cooking oil, and cooking fat. Since foods
and beverages comprising CTS and saccharide-derivatives of CTS have
the lipid-regulating activity, they can be used as compositions for
regulating the amount of lipids.
[0021] The lipid-regulating agent comprising CTS and/or its
saccharide-derivatives can be arbitrarily used for imparting
lipid-regulating activity to feeds, baits, pet foods for breeding
animals including domestic animals, poultries, honeybee, silkworm,
freshwater fish, sea fish, crustacea, etc., by incorporating the
agent into them. Further, since CTS and its saccharide-derivatives
regulate the functions of the intestines and inhibit the
re-absorption of bile acids in the intestine, the lipid-regulating
agent can be arbitrarily used for regulating the functions of the
intestines and/or regulating the metabolism of bile acids.
[0022] The methods for incorporating the lipid-regulating agent of
the present invention into objective compositions are not
specifically restricted. The agent can be incorporated into the
compositions before or after completion of their processing. The
methods for incorporating the agent can be arbitrarily selected
from the following conventional methods; mixing, kneading,
dissolving, melting, dispersing, suspending, emulsifying,
penetrating, dispersing, applying, attaching, spraying, coating,
injecting, crystallizing, and solidifying. Also, one or more these
methods can be arbitrarily combined.
[0023] It is preferable that the lipid-regulating agent of the
present invention comprises effective ingredients, CTS and/or its
saccharide-derivatives, in a total amount of about 0.1 w/w %
(hereinafter, "w/w%" is simply abbreviated as "%" in this
specification unless specified otherwise) or higher, more
preferably, 0.5% or higher, most preferably, 1.0% or higher. CTS
and/or its saccharide-derivatives can be used intact or in the form
of a saccharide composition further comprising other saccharides
such as glucose, isomaltose, maltose, oligosaccharides, dextrins,
etc., which are produced during the process of producing CTS and
its saccharide-derivatives, as lipid-regulating agent of the
present invention as long as it can be used for reducing and/or
keeping the amount of lipids in a living body. When the composition
comprising the lipid-regulating agent also comprises biologically
active substances, having an amino residue in its molecule, such as
amino acids as effective ingredients and reducing saccharides
including glucose, it is supposed that the effective ingredients
are deteriorated by the Maillard reaction and the quality of the
composition is also deteriorated. In such cases, it is preferable
to use the lipid-regulating agent comprising CTS and/or its
saccharide-derivatives in a total amount of 98% or higher, more
preferably, 99% or higher, most preferably, 99.5% or higher.
Further, a saccharide composition comprising CTS and/or its
saccharide-derivatives with a reduced reducibility, which is
prepared by hydrogenating other reducing saccharides, can be used
as the lipid-regulating agent of the present invention.
[0024] Since CTS and its saccharide-derivatives are stable
saccharides, they can be optionally incorporated into one or more
substances selected from the group consisting of saccharides such
as reducing saccharides, non-reducing saccharides except for CTS
and its saccharide-derivatives, cyclodextrin, sugar alcohols,
water-soluble polysaccharides; polyphenols such as flavonoids and
catechins; sweeteners, spices, acidifiers, seasonings, alcohols,
fatty acids and their salts, inorganic salts, emulsifiers, flavors,
colorings, antioxidants, and substances having a chelating
activity, according to the object such as improving the
dispersiency or filling, as far as they do not affect the effect
and quality of the composition comprising a lipid-regulating agent
of the present invention. If necessary, a suitable amount of one
ore more conventional substances such as preserves, seasonings,
sweeteners, stabilizers, alcohols, disinfectants, etc., can be used
with CTS and its saccharide-derivatives. The lipid-regulating
agents, thus obtained, are not restricted by their forms and any
form selected from the group consisting of syrup, paste,
massecuite, powder, crystal, granule, and tablet can be arbitrarily
used.
[0025] The lipid-regulating agent of the present invention can be
arbitrarily used after mixed with a suitable amount of one or more
saccharides or sweeteners selected from the group consisting of
starch hydrolyzate, glucose, maltose, trehalose, sucrose,
isomerized sugar, honey, maple sugar, isomaltooligosaccharides,
galactooligosaccharides, fructooligosaccharides,
nigerooligosaccharides, xylooligosaccharides,
agarooligosaccharides, chitooligosaccharides, beet
oligosaccharides, saccharide-derivatives of
.alpha.,.alpha.-trehalose such as .alpha.-glucosyl
.alpha.,.alpha.-trehalose, .alpha.-maltosyl
.alpha.,.alpha.-trehalose, etc., disclosed in Japanese Patent Kokai
No. 143,876/95, lactosucrose, sorbitol, maltitol, lactitol,
xylitol, erythritol, dihydrochalcone, stevioside,
.alpha.-glycosylstevioside, rebaudioside, glycyrrhizin, L-aspartyl
L-phenylalanine methyl ester, saccharine, glycine, alanine,
acesulfame K, and sucralose. The lipid-regulating agent of the
present invention can be used after mixed with fillers such as
dextrin, starch, lactose, etc.
[0026] The requisite intake per day of the lipid-regulating agent
of the present invention is not specifically restricted as far as
the agent exercises the lipid-regulating activity. It is preferable
to take the effective ingredients, CTS and/or its
saccharide-derivatives, in total, usually, in an amount of about
0.01 g or higher, more preferably, about 0.5 g or higher, most
preferably, about 1.2 g or higher, on a dry solid basis. In the
case of taking the agent in an amount of less than 0.01 g per day,
the lipid-regulating activity is insufficient. The requisite
intake-frequency per day of the lipid-regulating agent of the
present invention is not specifically restricted as far as it can
be enough to intake the amount of CTS and/or its
saccharide-derivatives for exercising the lipid-regulating
activity. The agent can be taken the requisite amount per day per
ones or several times. The lipid-regulating agent of the present
invention may rises diarrhea depending on the constitution when
large amount of the agent is taken. Usually, it is preferable to
intake the agent by dividing for several times. Particularly, it is
preferable to use the agent as a material of diet meal or to intake
the agent before or after taking meal. It is preferable to take the
lipid-regulating agent orally intact or in the form of a
composition such as foods and beverages, pharmaceuticals, and
medicated cosmetics. In the case of being impossible to intake
orally, the agent can be arbitrarily injected into stomach or
intestines directly by using a catheter or the like.
[0027] The following experiments explain a lipid-regulating agent
using CTS or the mixture of CTS and its saccharide-derivative(s) in
detail.
Experiment 1
[0028] As disclosed in International Publication No. WO 01/090,338,
it is known that CTS has a dietary fiber-like activity. Therefore,
the present inventors considered that CTS may have some effects on
living bodies. They investigated the effect of CTS on the lipid
metabolism using rats by administrating a feed comprising a
representative dietary fiber, cellulose or non-fiber feed as
controls.
Experiment 1-1
Feeding Test on Rat and the Measurement of the Weight
[0029] Fifty 5-weeks aged male Wister-rats, having a weight of 110
to 120 grams, commercialized by Charles River Japan, Kanagawa,
Japan, were fed on a non-fiber feed having a composition shown in
Table 1 for one week for habituation. After the habituation, the
rats were randomly divided into five groups and each group was fed
on either of feeds shown in Table 1, i.e., a non-fiber feed, a feed
in which cellulose was incorporated into the non-fiber feed to give
a content of 5% (hereinafter, abbreviated as "fiber feed"), a feed
in which powdery anhydrous crystalline CTS (purity of CTS: 99.5%),
prepared by the method of Example A-3 described later, was
incorporated into the non-fiber feed to give a content of 1, 2, or
5%, on a dry solid basis, and the feeding test was carried out for
four weeks. A fiber-feed and three kinds of feeds comprising CTS
were prepared to give the total content of cellulose or CTS and
corn starch of 44.75% to the total weight of each feed. The rats
were kept under the conditions of keeping the temperature at
25.degree. C., lighting and shading for 12 hours each/day, and
allowing the rats to eat the respective feed and water freely.
After the completion of the feeding test, weight of individuals in
each group was measured and an average weight and an average
increase of weight of each group during the test period were
calculated. The results are in Table 2. Also, the total amount of
feed fed to individual rat in each group during the 4-weeks test
period and an average amount of CTS taken per day per kg-weight-rat
were calculated and the results are in Table 2.
Determination of the Amount of Lipids in Blood Plasma
[0030] After the feeding test, each rat was fasted for one day and
incised under anesthesia with ether. Then, blood was collected from
the main vein of each rat using a syringe treated with 1% EDTA.
Each collected blood was centrifuged at 3,500 rpm for 10 minutes to
separate blood plasma and the contents of total cholesterol,
triglyceride, and phospholipids in the resulting blood plasma were
measured by using kits, "CHOLESTEROL C-TEST-WAKO",
"TRIGLYCERIDE-TEST-WAKO", and "PHOSPHOLIPID C-TEST WAKO",
respectively, commercialized by Wako Pure Chemical Industries,
Ltd., Osaka, Japan. In order to check the hepatic function
disorder, GOT activity in the blood plasma was measured using a
kit, "GOT-TEST-WAKO", commercialized by Wako Pure Chemical
Industries, Ltd., Osaka, Japan. The content of LDL-cholesterol was
calculated by subtracting the content of HDL-cholesterol from the
total content of cholesterol. The results are in Table 3. A
significant difference test was done with respect to the group fed
on fiber feed. In the case of cholesterol, a significant difference
test was done with respect to the group fed on non-fiber feed
because it was believed that cellulose has no activity of reducing
the amount of cholesterol by oral intake as described in
"SHOKUMOTSU-SENI KISO-TO-OYO (Dietary fiber, its basis and
application)" published by ASAKURA-SHOTEN in 1997.
Determination of the Amount of Lipids in Organs and Tissues
[0031] After collecting the blood described above, each rat was
killed by dislocating its cervical vertebrae and an atomized. Then,
adipose tissues surrounding intestinal membrane, kidney, and
testis, as well as liver and cecum, were collected. The wet-weight
of those adipose tissues was measured and the results are in Table
4. In the case of liver, the wet-weight and the amount of total
lipid, total cholesterol, triglyceride, and phospholipids were
measured and the results are in Table 5. The amount of total lipid,
total cholesterol, triglyceride, and phospholipids in the liver
were measured by the steps of homogenizing four parts by weight of
liver with four parts by weight of water using a homogenizer;
extracting lipid by repeating three-times the following procedure
of adding eight milliliters of a chloroform-methanol (2:1, by
volume) solution, stirring the mixture, and centrifuging (3,000
rpm, 15 min) to collect chloroform phase; concentrating the
resulting chloroform solution; and measuring those according to the
same procedure used in the case of lipids in blood plasma.
Measurement of the Cecal Content and Determination of the Amount of
Bile Acids in Cecal Content
[0032] Just after extirpating cecum as described above, its content
was collected and weighted. The concentration of bile acids was
measured by the steps of adding two milliliters of 80% (v/v)
methanol aqueous solution to 0.2 gram of the cecal content,
extracting bile acids at 70.degree. C. for 30 min, centrifuging
(3,500 rpm, 10 min) the mixture, drying the resulting supernatant
in a dessicator with P.sub.2O.sub.5 for overnight, and measuring
bile acids using a kit, "BILE ACID-TEST WAKO", commercialized by
Wako Pure Chemical Industries, Ltd., Osaka, Japan. The amount of
bile acids was calculated by multiplying the concentration of bile
acids and weight of the cecal content. The results are in Table 6.
The weight of cecal tissue was calculated by subtracting the
wet-weight of cecal content from the total wet-weight of extirpated
cecum. TABLE-US-00001 TABLE 1 Feed Ingredient Non-fiber Fiber 1%
(w/w)* CTS 2% (w/w)* CTS 5% (w/w)* CTS CTS 0 0 1.0 2.0 5.0
Cellulose 0 5.0 0 0 0 Corn starch 44.75 39.75 43.75 42.75 39.75
.alpha.-Starch 13.20 13.20 13.20 13.20 13.20 Casein 20.00 20.00
20.00 20.00 20.00 Sucrose 10.00 10.00 10.00 10.00 10.00 Soybean oil
7.00 7.00 7.00 7.00 7.00 Mineral mix 3.50 3.50 3.50 3.50 3.50
Vitamin mix 1.00 1.00 1.00 1.00 1.00 D,L-Methionine 0.30 0.30 0.30
0.30 0.30 Choline bitartrate 0.25 0.25 0.25 0.25 0.25 t-Butyl
hydroquinone 0.0014 0.0014 0.0014 0.0014 0.0014 *on a dry solid
basis
[0033] TABLE-US-00002 TABLE 2 Feed Measurement items** Non-fiber
Fiber 1% (w/w) CTS 2% (w/w) CTS 5% (w/w) CTS Weight 342 345 337 342
322* (g/individual) Increase of weight 168 171 164 169 149*
(g/individual/ 28 days) Total amount of feed 575 580 593 601 561
taken (g/individual/ 28 days) The amount of CTS 0 0 0.63 1.25 3.1
taken per weight per day (g/kg/day) *differ significantly (p <
0.05) **Significant difference is evaluated with respect to the
group fed on feed comprising fiber.
[0034] TABLE-US-00003 TABLE 3 Feed Measurement items** Non-fiber
Fiber 1% (w/w) CTS 2% (w/w) CTS 5% (w/w) CTS Total cholesterols
69.8 64.1 67.1 66.1 59.4* (mg/dl) Triglycerides 41.0 48.2 44.2
28.7* 21.7* (mg/dl) Phospholipids 125 115 116 115 107 (mg/dl) GOT
10.5 10.1 10.3 10.2 10.7 (IU) *differ significantly (p < 0.05)
**In the case of cholesterol, significant difference is evaluated
with respect to the group fed on non-fiber feed. In other cases,
significant difference is evaluated with respect to the group fed
on feed comprising fiber.
[0035] TABLE-US-00004 TABLE 4 Feed Measurement items** Non-fiber
Fiber 1% (w/w) CTS 2% (w/w) CTS 5% (w/w) CTS Adipose surrounding
4.4 4.3 3.7 3.1* 1.9* intestinal membrane (g/individual) Adipose
surrounding 5.3 4.8 3.7* 2.9* 2.1* kidney (g/individual) Adipose
surrounding 5.3 5.3 4.0* 3.9* 3.1* testis (g/individual) *differ
significantly (p < 0.05) **Significant difference is evaluated
with respect to the group fed on a feed comprising fiber.
[0036] TABLE-US-00005 TABLE 5 Feed Measurement items** Non-fiber
Fiber 1% (w/w) CTS 2% (w/w) CTS 5% (w/w) CTS Weight of liver 8.8
8.7 8.4 8.6 8.1 (g/individual) Total lipids in liver 645 586 510
598 575 (mg/individual) Total cholesterols in 39.5 36.8 35.9 7.2
35.4 liver (mg/individual) Triglycerides in 329 265 186 254 239
liver (mg/individual) Phospholipids in 154 139 140 149 142 liver
(mg/individual) *differ significantly (p < 0.05) **In the case
of cholesterol, significant difference is evaluated with respect to
the group fed on a non-fiber feed. In other cases, significant
difference is evaluated with respect to the group fed on feed
comprising fiber.
[0037] TABLE-US-00006 TABLE 6 Feed Measurement items** Non-fiber
Fiber 1% (w/w) CTS 2% (w/w) CTS 5% (w/w) CTS Weight of cecal tissue
0.85 0.87 1.12* 1.19* 1.39* (g/individual) Weight of cecal 2.1 2.5
2.4 3.0* 3.5* content (g/individual) Bile acids in cecum 0.91 0.82
1.15* 1.36* 1.53* (.mu.mol) *differ significantly (p < 0.05)
**Significant difference is evaluated with respect to the group fed
on the fiber-feed.
Effects of the Administration of CTS on the Weight of Rat and the
Amount of Feed Intake
[0038] As evident from Table 2, in the case of the group fed on the
feed comprising 5% CTS, significant difference of the weight and
the inhibition of weight increase were observed in comparison with
a group fed on the fiber-feed. No significant difference was
observed in the total amount of feed intake among any group during
the test period. Effect of the administration of CTS on the amount
of lipids As evident from Table 3, as regards the amount of lipids
in the blood plasma, total amount of cholesterol in the group fed
on a feed comprising 5% CTS is significantly lower than that in the
group fed on non-fiber feed. The amounts of triglyceride in the
groups fed on feeds comprising 2% and 5% CTS were significantly
lower than that in the group fed on a fiber-feed. Significant
differences were not observed in the amount of phospholipids and
GOT activity among any groups. As evident from Table 4, the
accumulation of lipids around intestine, kidney, and testis in the
groups fed on feeds comprising 2% and 5% CTS was significantly
lower than those in the group fed on a fiber-feed. Also, the
accumulation of lipids around kidney and testis in the group fed on
a feed comprising 1% CTS was significantly lower than those in the
group fed on a fiber-feed. As evident from Table 5, the amounts of
triglyceride in liver in the groups fed on feeds comprising CTS
were slightly lower than those in the groups fed on a non-fiber
feed or a fiber-feed, but no significant difference was observed
because of varying individual values. No significant difference was
observed in other lipids.
Effects of the Administration of CTS on the Weight of Cecal
Contents and the Amount of Bile Acids in Cecum
[0039] As evident from Table 6, the weight of cecal tissue and the
amount of cecal content and that of bile acids in cecum in the
groups fed on feeds comprising 2% and 5% CTS were significantly
higher than those in the group fed on a fiber-feed. Also, the
weight of cecal tissue and the amount of bile acids in cecum in the
group fed on a feed comprising 1% CTS were significantly higher
than those in the group fed on a fiber-feed.
[0040] From those results, it was revealed that CTS has an effect
of regulating the amount of lipids such as triglycerides in blood
plasma and lipids around organs (visceral lipids), and those
effects are very stronger than those of cellulose which is a
representative dietary fiber. Particularly, since CTS showed
significant lipid-regulating effects on triglyceride in blood
plasma and perivisceral lipids and tend to lower triglyceride in
liver, the lipid-lowering effect in serum is not caused by the
mechanism of accumulating triglyceride in adipose tissue and but by
lowering lipids in the living body in rats fed on CTS. The effect
of regulating the amount of lipids, i.e., the effect of lowering
the amount of lipids in the living body depends on the intake
amount of CTS. Varying with the kinds of lipids, the effects of
lowering the amount of lipids was observed even in the case of
using a feed with a CTS content of 1% (the average intake of CTS
per day was 0.63 g per individual). It was confirmed that a
remarkable lipid-regulating effect was observed in the case of
using feeds with a CTS content of 2% or higher (the average intake
of CTS per day was 1.25 g or higher per individual). Further, the
effect of lowering the amount of cholesterols was observed in the
case of rats fed on a feed with CTS content of 5%. It is believed
that the effect is not observed in cellulose. Since the amount of
bile acids involving the absorption of lipids was increased in
intestinal cecum, CTS has a potential of inhibiting the
re-absorption of bile acids and the absorption of lipids by small
intestine. It is suggested that one of the mechanism of regulating
the amount of lipids by CTS is the inhibition of the re-absorption
of bile acids by small intestine.
[0041] GOT values, which are markers of functional disorder of
liver, of rats were not significantly changed during the test
period regardless of the intake of CTS. These results indicate that
the lipid-regulating activity of CTS is caused by disorder of
liver. Although the concrete data are not shown, two individuals in
ten individuals of rats, fed on a feed with CTS content of 5%,
showed a symptom of diarrhea for 2-3 days after initial intake of
CTS and then cured. This result indicates that CTS is a hardly
digestible saccharide, and these coincidents with the results
disclosed in International Publication No. WO 01/090,338 by the
same applicant as the present invention. The symptom of diarrhea
was not observed in rats fed on a feed with CTS content of 2%. The
result of curing the symptom of diarrhea indicates that intestinal
bacteria of rats adjust with CTS gradually.
Experiment 1-2
Effect of the Administration of a Saccharide Comprising CTS and its
Saccharide-Derivatives on the Lipids of Rat
[0042] From the results in Experiment 1-1, it was confirmed that
CTS has a lipid-regulating activity for rat. Successively, a test
was carried out to confirm that a saccharide comprising CTS and its
saccharide-derivatives has the same activity as in the case of CTS
only as follows. Further, the amount of bile acids which are known
to involve the lipid-regulation and GOT activity which is used as
an index of hepatic function disorder were measured. The amount of
LDL-cholesterol was measured along with the amount of total
cholesterol to investigate that the decline of the amount of
cholesterol observed in Experiment 1-1 is caused by decreasing the
amount of LDL-cholesterol, which is recognized as a cause of
arterial sclerosis and cardiac infarction, or not. A significant
difference test was done with respect to the group fed on the fiber
feed. In the case of cholesterol, significant difference test was
done with respect to the group fed on the non-fiber feed.
Feeding Test on Rat and Measurement of the Weight
[0043] An experiment for investigating the effects of the
administration of a saccharide comprising CTS and its
saccharide-derivatives on the amount of lipids of rat was carried
out as follows:
[0044] Fifty 5-weeks aged male Wister-rats, having a weight of 110
to 120 grams, commercialized by Charles River Japan, Kanagawa,
Japan, were fed on a non-fiber feed having a composition shown in
Table 7 for one week for habituation. After the habituation, the
rats were randomly divided 10 individuals each into five groups and
each group was fed on either of feeds shown in Table 7, i.e., a
non-fiber feed, a fiber feed, a feed in which powdery product,
prepared by spray-drying a syrup comprising 35.2%, on a dry solid
basis, of CTS and 15.6%, on a dry solid basis of its
saccharide-derivatives by the method of Example A-2 described
after, was incorporated into the non-fiber feed to give a total
content of CTS and its saccharide-derivative of 1, 2, or 5%, on a
dry solid basis, and the feeding test was carried out for four
weeks. A fiber-feed and three kinds of feed comprising a saccharide
comprising CTS and its saccharide-derivatives were prepared to give
the total content of cellulose or a saccharide, comprising CTS and
its saccharide-derivatives, and corn starch of 44.75% to the total
weight of the feed. After the completion of the feeding test,
weight of individuals in each group was measured and calculated an
average weight of a group and an average increase of weight in the
test period. The results are in Table 8. Also, the total amount of
feed fed to individual rat in each group during the 4-weeks test
period and an average amount of CTS or the total of CTS and its
saccharide-derivatives intakened per day per kg-weight-rat were
calculated and are in Table 8.
Determination of the Amount of Lipids in Blood Plasma
[0045] After the feeding test, the contents of total cholesterol,
HDL-cholesterol, triglyceride, and phospholipids and GOT activity
in the blood plasma were measured according to the methods
described in Experiment 1-1. The content of LDL-cholesterol was
calculated by subtracting the content of HDL-cholesterol from the
total content of cholesterol. The content of HDL-cholesterol was
measured using a kit, "HDL-CHOLESTEROL-TEST-WAKO", commercialized
by Wako Pure Chemical Industries, Ltd., Osaka, Japan. The results
are in Table 9.
Determination of the Amount of Lipids in Organs or Tissues
[0046] After collecting the blood described above, the wet-weights
of adipose tissues surrounding intestinal membrane, kidney, and
testis were measured according to the method described in
Experiment 1-1 and the results are in Table 10. The wet-weight of
liver and the amount of total lipids, total cholesterol,
triglycerides, and phospholipids in the liver were measured and the
results are in Table 11.
Measurement of Weight of Cecal Contents and the Determination of
the Amount of Bale Acid in Cecum
[0047] Just after extirpating cecum as described above, its content
was collected and the weight of cecal content and the amount of
bile acids were measured according to the methods described in
Experiment 1-1. The results are in Table 12. TABLE-US-00007 TABLE 7
Feed 1% (w/w)* 2% (w/w)* 5% (w/w)* Ingredient Non-fiber Fiber CTS +
SDCTS** CTS + SDCTS** CTS + SDCTS** Powdery composition 0 0 1.97
3.94 9.84 comprising CTS and SDCTS** Cellulose 0 5 0 0 0 Corn
starch 44.75 39.75 42.78 40.81 34.91 .alpha.-Starch 13.20 13.20
13.20 13.20 13.20 Casein 20.00 20.00 20.00 20.00 20.00 Sucrose
10.00 10.00 10.00 10.00 10.00 Soybean oil 7.00 7.00 7.00 7.00 7.00
Mineral mix 3.50 3.50 3.50 3.50 3.50 Vitamin mix 1.00 1.00 1.00
1.00 1.00 D,L-Methionine 0.30 0.30 0.30 0.30 0.30 Choline
bitartrate 0.25 0.25 0.25 0.25 0.25 t-Butyl hydroquinone 0.0014
0.0014 0.0014 0.0014 0.0014 *on a dry solid basis
**Saccharide-derivative of CTS
[0048] TABLE-US-00008 TABLE 8 Feed 1% (w/w) 2% (w/w) 5% (w/w)
Measurement items** Non-fiber Fiber CTS + SDCTS CTS + SDCTS CTS +
SDCTS Weight 371 349 359 356 351* (g/individual) Increase of weight
205 182 192 189 185* (g/individual/ 28 days) Total amount of feed
584 580 583 588 586 taken (g/individual/ 28 days) The total amount
of CTS 0 0 0.58 1.18 2.98 and SDCTS taken (0.38)*** (0.81)***
(2.05)*** per weight per day (g/kg/day) *differ significantly (p
< 0.05) **Significant difference is evaluated with respect to
the group fed on the fiber-feed. ***The amount of CTS only
[0049] TABLE-US-00009 TABLE 9 Feed 1% (w/w) 2% (w/w) 5% (w/w)
Measurement items** Non-fiber Fiber CTS + SDCTS CTS + SDCTS CTS +
SDCTS Total cholesterol 58.9 55.3 45.7* 49.4* 44.5* (mg/dl)
HDL-cholesterol 32.8 32.0 24.8* 29.8 26.2* (mg/dl) LDL-cholesterol
26.1 23.3 20.9* 19.6* 18.3* (mg/dl) Percentage of 44.1 42.3 46.4
40.1 41.2 LDL-cholesterol to total cholesterol (%) Triglycerides
94.2 72.9 65.0 53.8 32.5* (mg/dl) Phospholipids 108.7 98.2 85.6*
90.7 83.9* (mg/dl) GOT 9.3 10.7 11.2 11.1 8.6* (IU) *differ
significantly (p < 0.05) **In the case of cholesterol,
significant difference is evaluated with respect to the group fed
on the non-fiber feed. In other cases, significant difference is
evaluated with respect to the group fed on the fiber-feed.
[0050] TABLE-US-00010 TABLE 10 Feed 1% (w/w) 2% (w/w) 5% (w/w)
Measurement items** Non-fiber Fiber CTS + SDCTS CTS + SDCTS CTS +
SDCTS Adipose surrounding 5.8 5.7 5.4 4.2* 3.9* intestinal membrane
(g/individual) Adipose surrounding 7.4 6.9 5.5 4.4* 3.8* kidney
(g/individual) Adipose surrounding 8.0 6.6 5.8 4.9* 4.8* testis
(g/individual) *differ significantly (p < 0.05) **Significant
difference is evaluated with respect to the group fed on the
fiber-feed.
[0051] TABLE-US-00011 TABLE 11 Feed 1% (w/w) 2% (w/w) 5% (w/w)
Measurement items** Non-fiber Fiber CTS + SDCTS CTS + SDCTS CTS +
SDCTS Weight of liver 9.8 9.1 9.0 9.0 8.7 (g/individual) Total
lipids in liver 623 653 605 598 550* (mg/individual) Total
cholesterols in 38.3 43.4* 43.3* 39.3 38.0 liver (mg/individual)
Triglycerides in 266 292 256 239* 220* liver (mg/individual)
Phospholipids in 153 165 176 169 153 liver (mg/individual) *differ
significantly (p < 0.05) **In the case of cholesterol,
significant difference is evaluated with respect to the group fed
on the non-fiber feed. In other cases, significant difference is
evaluated with respect to the group fed on the fiber feed.
[0052] TABLE-US-00012 TABLE 12 Feed 1% (w/w) 2% (w/w) 5% (w/w)
Measurement items** Non-fiber Fiber CTS + SDCTS CTS + SDCTS CTS +
SDCTS Weight of cecal 2.23 2.38 2.63 2.97* 4.32* content
(g/individual) Bile acids in cecal 14.3 16.1 23.8* 25.0* 35.4*
content (.mu.mol/individual) *differ significantly (p < 0.05)
**Significant difference is evaluated with respect to the group fed
on the fiber-feed.
Effects of the Administration of CTS and its Saccharide-Derivatives
on the Weight of Rat and the Amount of Feed Intake
[0053] As evident from Table 8, significant differences on the
weight and the amount of feed taken were not observed among any
groups.
Effect of the Administration of CTS and its Saccharide-Derivative
on the Amount of Lipids in Blood Plasma
[0054] As evident from Table 9, the amounts of total cholesterol
and LDL-cholesterol in blood plasma in the groups fed on a feed
comprising 1, 2, or 5%, on a dry solid basis, of CTS were
significantly lower than those in the group fed on non-fiber feed.
Further, the ratio of the amount of LDL-cholesterol to the amount
of total cholesterol in blood plasma is not significantly changed
in any groups. The amount of triglyceride in blood plasma was
lowered depending on the contents of CTS and its
saccharide-derivatives in the feed. That in the group fed on the
feed comprising CTS and its saccharide-derivatives of 5%, on a dry
solid basis, was significantly lower than that in the group fed on
the fiber-feed. The amounts of phospholipids in the groups fed on
the feed CTS and its saccharide-derivatives of 1 or 5%, on a dry
solid basis, were significantly lower than that in the group fed on
the fiber-feed.
Effect of the Administration of CTS and its Saccharide-Derivative
on the Amount of Lipids in Tissues
[0055] As evident from Table 10, the accumulation of lipids around
intestinal membrane, kidney, and testis was inhibited depending on
the content of CTS and its saccharide-derivatives in the group fed
on the feed comprising CTS and its saccharide-derivatives. The
accumulation of lipids in the group fed on the feed comprising CTS
and its saccharide-derivatives of 2or5%, on a dry solid basis, were
significantly lower than that in the group fed on the fiber-feed.
As evident from Table 11, as regard to the liver, the total amount
of lipids and the amount of triglycerides were lowered depending on
the content of CTS and its saccharide-derivatives in the group fed
on the feed comprising CTS and its saccharide-derivatives. The
total amount of lipids in the liver in the group fed on the feed
comprising CTS and its saccharide-derivative of 5%, on a dry solid
basis, was significantly lower than that in the group fed on the
fiber-feed. The amounts of triglycerides in the liver in the groups
fed on the feed comprising CTS and its saccharide-derivative of 2
or 5%, on a dry solid basis, were significantly lower than that in
the group fed on the fiber-feed. The amounts of total cholesterol
in the liver in the groups fed on the feed comprising CTS and its
saccharide-derivative of 1%, on a dry solid basis, were
significantly higher than that in the group fed on the non-fiber
feed. The weight of liver and the amount of phospholipids were not
significantly different among any groups.
Effects of the Administration of CTS and its Saccharide-Derivative
on the Weight of Cecal Contents and the Amount of Bile Acids in
Cecum
[0056] As evident from Table 12, the amount of cecal content and
that of bile acids in cecum were increased depending on the total
amount, on a dry solid basis, of CTS and its saccharide-derivatives
in the groups fed on feeds comprising CTS and its
saccharide-derivatives. The amount of cecal contents in the groups
fed on feeds comprising 2% and 5% of CTS and its
saccharide-derivatives were significantly higher than that in the
group fed on a fiber-feed. The amount of bile acids in cecum in any
group fed on a feed comprising CTS and its saccharide-derivatives
were significantly higher than that in the group fed on a
fiber-feed.
[0057] These results indicate that saccharides comprising CTS and
its saccharide-derivatives also have the lipid-regulating effect as
in the case of CTS. It was confirmed that the effects of regulating
the amount of lipids depend on the total amount of CTS and its
saccharide-derivatives taken. Varying with the kinds of lipids, the
effects of lowering the amount of lipids was observed even in the
case of using a feed with a total content of CTS and its
saccharide-derivatives of 1%, on a dry solid basis (the average
intake of CTS per day was 0.56 g per individual). It was confirmed
that a remarkable lipid-regulating effect was observed in the case
of using feeds with a total content of CTS and its
saccharide-derivatives of 2% or higher, on a dry solid basis (the
average intake of CTS per day was 1.18 g or higher per individual).
Since the amount of bile acids was increased in intestinal cecum as
in the case of using CTS only, it is suggested that both CTS and
its saccharide-derivatives have a potential of inhibiting the
re-absorption of bile acids and the absorption of lipids by small
intestine. In comparison with the feed comprising CTS only, used in
Experiment 1-1, a relative CTS content of the feed comprising CTS
and its saccharide-derivatives, used in Experiment 1-2, is about
70%. However, almost equivalent lipid-regulating effects are
observed in the both Experiments. This result indicates that
saccharide-derivatives of CTS have the lipid-regulating activity as
in the case of CTS. Although GOT values of rats significantly
decreased depending on the amount of intake of CTS in rats fed on
the feed comprising CTS and its saccharide-derivatives, the degree
of the variation was small. Therefore, it is not believed that
these rats develop the disorder of liver.
[0058] From the experimental results described above, it is
revealed that a composition comprising CTS and/or its
saccharide-derivatives can be used for regulating the amount of
lipids in a living body.
[0059] The following concretely explains a lipid-regulating agent,
comprising CTS and/or its saccharide-derivative(s) as an effective
ingredients, of the present invention in Examples A; and a
composition, comprising the lipid-regulating agent, of the present
invention in Examples B. However, the present invention is not
restricted by them.
EXAMPLES A
Lipid-Regulating Agent Comprising CTS and/or its
Saccharide-Derivartive(s) as an Effective Ingredient(s)
EXAMPLE A-1
[0060] According to the method of Example A-2 disclosed in
International Publication No. WO 02/010,361, a lipid-regulating
agent in a syrupy form with a concentration of 80%, containing, on
a dry solid basis, 0.6% glucose, 1.5% isomaltose, 12.3% maltose,
63.5% CTS, 5.2% saccharide-derivatives of CTS where one or more
glucose molecules were bound to CTS, and 16.9% other saccharides,
was prepared from potato starch. The product can be advantageously
used intact or for preparing a composition such as foods and
beverages, medicated cosmetics, pharmaceuticals, feeds, pet-foods,
etc., for regulating the amount of lipids by incorporating it into
materials such as edible materials and pharmaceutical materials, or
intermediate products.
EXAMPLE A-2
[0061] According to the method of Example A- 9 disclosed in
International Publication No. WO 02/010,361 (except for treatments
by .alpha.-glucosidase and glucoamylase), a lipid-regulating agent
in a syrupy form with a concentration of 73%, containing, on a dry
solid basis, 4.1% glucose, 8.1% disaccharides including maltose and
isomaltose, 4.6% trisaccharides including maltotriose, 35.2% CTS,
15.6% saccharide-derivatives of CTS where one or more glucose
molecules were bound to CTS, and 32.4% other saccharides, was
prepared from corn starch. The product can be advantageously used
intact or for preparing a composition such as foods and beverages,
medicated cosmetics, pharmaceuticals, feeds, pet-foods, etc., for
regulating the amount of lipids by incorporating it into materials
such as edible materials and pharmaceutical materials, or
intermediate products.
EXAMPLE A-3
[0062] A syrup comprising CTS, prepared from corn starch according
to the method of Example A-4 disclosed in International Publication
No. WO 02/010,361, was purified, concentrated, died, and
crystallized according to the method of Example A-6 also disclosed
in the above International Publication to produce a powdery
lipid-regulating agent, crystalline CTS pentahydrate preparation
having a CTS purity of 99.6%. The product can be advantageously
used intact or for preparing a composition such as foods and
beverages, medicated cosmetics, pharmaceuticals, feeds, pet-foods,
etc., for regulating the amount of lipids by incorporating it into
materials such as edible materials and pharmaceutical materials, or
intermediate products.
[0063] The above crystalline CTS pentahydrate preparation was dried
according to the method of Experiment 31 and 32 to produce two
kinds of lipid-regulating agent, powdery crystalline CTS
monohydrate and powdery anhydrous crystalline CTS, respectively.
Both lipid-regulating agents can be advantageously used intact or
for preparing a composition such as foods and beverages, medicated
cosmetics, pharmaceuticals, feeds, pet-foods, etc., for regulating
the amount of lipids by incorporating it into materials such as
edible materials and pharmaceutical materials, or intermediate
products.
EXAMPLE A-4
[0064] Forty parts by weight of "MABIT", anhydrous crystalline
maltitol commercialized by Hayashibara Shoji Inc, Okayama, Japan,
was admixed with 60 parts by weight of crystalline CTS
pentahydrate, obtained in Example A-3, to make into a powdery
lipid-regulating agent. The product can be advantageously used
intact or for preparing a composition such as foods and beverages,
medicated cosmetics, pharmaceuticals, feeds, pet-foods, etc., for
regulating the amount of lipids by incorporating it into materials
such as edible materials and pharmaceutical materials, or
intermediate products.
EXAMPLE A-5
[0065] Fifty parts by weight of "TREHA.RTM.",
.alpha.,.alpha.-trehalose commercialized by Hayashibara Shoji Inc,
Okayama, Japan, was admixed with 50 parts by weight of crystalline
CTS pentahydrate, obtained in Example A-3, to make into a powdery
lipid-regulating agent. The product can be advantageously used
intact or for preparing a composition such as foods and beverages,
medicated cosmetics, pharmaceuticals, feeds, pet-foods, etc., for
regulating the amount of lipids by incorporating it into materials
such as edible materials and pharmaceutical materials, or
intermediate products. Further, the product can be easily used,
intact or after incorporating with a sugar ester and the like, in
the forms of granule or tablets by granulating or making into
tablet.
EXAMPLE A-6
[0066] "TREHA.RTM.", a food-grade hydrous crystalline a,a-trehalose
commercialized by Hayashibara Shoji Inc., Okayama, Japan, was
dissolved in water and the resulting solution was concentrated
under reduced pressure with heating to 60.degree. C. to prepare a
solution having a .alpha.,.alpha.-trehalose concentration of 75%. A
powdery hydrous crystalline .alpha.,.alpha.-trehalose, having a
.alpha.,.alpha.-trehalose purity of 99.8%, was prepared from the
solution by the steps of crystallizing .alpha.,.alpha.-trehalose by
cooling the solution to the ambient temperature, washing the
resulting crystal twice with water, drying the resulting crystal,
and pulverizing the dried crystal. Fifty parts by weight of the
powdery hydrous crystalline .alpha.,.alpha.-trehalose and 50 parts
by weight of crystalline CTS pentahydrate were mixed to homogeneity
to make into a powdery lipid-regulating agent. The product can be
advantageously used intact or for preparing a composition such as
foods and beverages, medicated cosmetics, pharmaceuticals, feeds,
pet-foods, etc., for regulating the amount of lipids by
incorporating it into materials such as edible materials and
pharmaceutical materials, or intermediate products. Since the
product was composed by CTS and .alpha.,.alpha.-trehalose with high
purities, it has a low reactivity and high stability. Therefore,
the product can be preferably used to produce a composition,
comprising an amino-compound(s) which causes the Maillard reaction
with reducing sugars and having a fear of quality deterioration.
Further, the product can be easily used, intact or after
incorporating with a sugar ester and the like, in the forms of
granule or tablets by granulating or making into tablet.
EXAMPLE A-7
[0067] Two parts by weight of ascorbic acid, one part by weight of
vitamin E, and 0.5 part by weight of glycerin-fatty acid ester were
admixed with 70 parts by weight of a syrup, comprising the mixture
of CTS and its saccharide-derivatives, obtained in Example A-1. The
product can be advantageously used intact or for preparing a
composition such as foods and beverages, medicated cosmetics,
pharmaceuticals, feeds, pet-foods, etc., for regulating the amount
of lipids by incorporating it into materials such as edible
materials and pharmaceutical materials, or intermediate
products.
EXAMPLE A-8
[0068] Two parts by weight of ascorbic acid 2-glucoside
commercialized by Hayashibara Biochemical Laboratories Inc.,
Okayama, Japan, and two parts by weight of ".alpha.G-RUTIN", an
enzymatically modified rutin commercialized by Toyo Sugar Refining
Co; ltd., Tokyo, Japan, were admixed with 70 parts by weight of
crystalline CTS pentahydrate, obtained in Example A-3 to produce a
powdery mixture. The product can be advantageously used intact or
for preparing a composition such as foods and beverages, medicated
cosmetics, pharmaceuticals, feeds, pet-foods, etc., for regulating
the amount of lipids by incorporating it into materials such as
edible materials and pharmaceutical materials, or intermediate
products.
EXAMPLE B
Composition for Regulating the Amount of Lipids Comprising a
Lipid-Regulating Agent which Comprises CTS and/or its
Saccharide-Derivative(s) as an Effective Ingredient(s)
EXAMPLE B-1
Table Sugar for Regulating the Amount of Lipids
[0069] Fifty parts by weight of a powdery lipid-regulating agent,
crystalline CTS pentahydrate prepared by the method of Example A-3,
46 parts by weight of anhydrous crystalline maltitol, three parts
by weight of ".alpha.G-HESPERIDIN", glucosyl-hesperidin
commercialized by Toyo Sugar Refining Co; ltd., Tokyo, Japan, one
part by weight of sucralose commercialized by San-Ei Gen F.F.I.,
Inc., Osaka, Japan, were dissolved into 200 parts by weight of
water and then the mixture was spray-dried by the conventional
method to make into powdery sweetener for regulating the amount of
lipids. Since CTS and glucosyl-hesperidin regulates the amount of
lipids in the living body, the product can be preferably used as a
table sugar for the purpose of diet, preventing lifestyle-related
disease, or for patients of lifestyle-related disease such as
adiposis and hypertension, requiring the restriction of lipids
intake.
EXAMPLE B-2
Sweetener for Regulating the Amount of Lipids
[0070] Five parts by weight of powdery lipid-regulating agent,
crystalline CTS monohydrate prepared in Example A-3, 94.5 parts by
weight of "MABIT.RTM.", powdery anhydrous crystalline maltitol
commercialized by Hayashibara Shoji Inc., Okayama, Japan, and 0.5
part by weight of "ASPERTAME",
L-aspartyl-L-phenylalanine-methyl-ester commercialized by Ajinomoto
Co., Inc., Tokyo, Japan, were mixed to homogeneity and granulated
by the conventional method to make into granule sweetener for
regulating the amount of lipids. CTS in the product regulates
lipids in the living body and the product has a lower calorie than
sucrose. Since one can keep off calorie by taking the product, the
product can be preferably used as a sweetener for the purpose of
diet, preventing lifestyle-related disease, or for patients of
lifestyle-related disease such as adiposis and hyperlipemia,
requiring the restriction of intake of sugars and lipids. Further,
the product can be used as a sweetener for pharmaceuticals.
EXAMPLE B-3
Powdery Fat for Regulating the Amount of Lipids
[0071] One hundred parts by weight of soybean salad oil, one part
by weight of lecithin, and 10 parts by weight of water were mixed
at an ambient temperature, and then admixed with 100 parts by
weight of powdery lipid-regulating agent prepared in Example A-5,
and the mixture was powderized and shifted to make into powdery fat
for regulating the amount of lipids. Since the product comprises
CTS, lipids in the living body is regulated when one intakes foods
and beverage, feed, pet food, etc., prepared with the product.
Therefore, the product can be preferably used for the purpose of
diet, preventing lifestyle-related disease, or as materials for
foods of patients of lifestyle-related disease such as adiposis and
hyperlipemia, requiring the restriction of intake of sugars and
lipids, and for feeds or pet foods of animals which are required to
regulate lipids in the body.
EXAMPLE B-4
Vegetable Juice for Regulating the Amount of Lipids
[0072] To 97.5 parts by weight of commercial vegetable juice, one
part by weight of partial xyloglucan hydrolyzate, one part by
weight of lipid-regulating agent in a syrupy form, prepared in
Example A-2, and 0.5 part by weight of glucosyl-naringin were added
and dissolved to make into vegetable juice for regulating the
amount of lipids. Since the product comprises CTS, its
saccharide-derivative, partial xyloglucan hydrolyzate,
glucosyl-naringin, and dietary fiber from vegetable, lipids in the
living body are regulated when one intakes foods and beverage,
feed, pet food, etc., prepared with the product. Therefore, the
product can be preferably used for the purpose of diet, preventing
lifestyle-related disease, or as a healthy supplement for patients
of lifestyle-related disease such as adiposis and hyperlipemia,
requiring the restriction of lipids intake. Further, since CTS and
its saccharide-derivative decreases bad taste and smell of
vegetable, the product is a vegetable juice easy to drink.
EXAMPLE B-5
Beer for Regulating the Amount of Lipids
[0073] "NB BEER BASE SET", a commercial kit for preparing beer
commercialized by Mail-Order Club of Tokyu Hands Inc., Tokyo,
Japan, was purchased. Two parts by weight of lipid-regulating agent
in a syrupy form, prepared by the method of Example A-1 was admixed
with 100 parts by weight of the solution for fermentation in the
kit and prepared beer according to the manual attached with the
kit. Since the lipids in the living body are regulated by drinking
the product, the product can be preferably used as a beer for the
purpose of diet and preventing lifestyle-related disease. Further,
since the product showed decreased bad taste and/or bad smell which
is characteristic of beer, the product is a delicious beer with
good aftertaste.
EXAMPLE B-6
Shochu-Based Beverage for Regulating the Amount of Lipids
[0074] Four parts by weight of a lipid-regulating agent in a syrupy
form, prepared by the method of Example A-1, and ume (Japanese
apricot) flavor were admixed with a diluted shochu prepared by
diluting commercial shochu with soda water and stirred to make into
a shochu-based beverage with alcohol content of 6%. Since the
lipids in the living body are regulated by drinking the product,
the product can be preferably used as an alcohol beverage for the
purpose of diet and preventing lifestyle-related disease. Further,
since the product showed decreased bad taste and/or bad smell which
is characteristic of shochu, the product is a delicious
shochu-based beverage with good aftertaste.
EXAMPLE B-7
Powdery Carrot Extract for Regulating the Amount of Lipids
[0075] Two parts by weight of hydrous crystalline trehalose and
four parts by weight of a lipid-regulating agent in a syrupy form,
prepared in Example A-1, were admixed with one part by weight of
5-folds concentrated carrot extract and dissolved by stirring. The
resulting mixture was spray-dried by the conventional method to
make into a powdery carrot extract for regulating the amount of
lipids. Since the product comprises CTS and its
saccharide-derivative, lipids in the living body are regulated when
one intakes foods and beverage, feed, pet food, etc., prepared with
the product. Therefore, the product can be preferably used for the
purpose of diet, preventing lifestyle-related disease, or as a
healthy supplement for patients of lifestyle-related disease such
as adiposis and hyperlipemia, requiring the restriction of lipids
intake.
EXAMPLE B-8
Powdery Royal Jelly for Regulating the Amount of Lipids
[0076] Nine parts by weight of a lipid-regulating agent, prepared
by mixing equal amount of crystalline CTS monohydrate and anhydrous
crystalline CTS, both prepared in Example A-3, was admixed with one
part by weight of frozen raw royal jelly and the mixture was
pulverized by the conventional method to make into powdery raw
royal jelly for regulating the amount of lipids. Since the product
comprises CTS and royal jelly, lipids in the living body are
regulated when one intakes foods and beverage, feed, pet food,
etc., prepared with the product. Therefore, the product can be
preferably used for the purpose of diet, preventing
lifestyle-related disease, or as a healthy supplement for patients
of lifestyle-related disease such as adiposis and hyperlipemia,
requiring the restriction of lipids intake.
EXAMPLE B-9
Chocolate Cookie for Regulating the Amount of Lipids
[0077] Chocolate cookie for regulating the amount of lipids was
prepared by convention al method using 140 parts by weight of wheat
flour (soft flour), 90 parts by weight of butter, 115 parts by
weight of chocolate, 360 parts by weight of sucrose, 200 parts by
weight of whole egg, 200 parts by weight of almond, and 50 parts by
weight of a powdery lipid-regulating agent, crystalline CTS
monohydrate prepared by the method of Example A-3. Since the lipids
in the living body are regulated by CTS, the product can be
preferably used for the purpose of diet and preventing
lifestyle-related disease or as a confectionary for patients of
lifestyle-related disease such as adiposis and hyperlipemia,
requiring the restriction of lipids intake.
EXAMPLE B-10
Jelly for Regulating the Amount of Lipids
[0078] Two hundred parts by weight of pureed raspberry, 46 parts by
weight of sucrose, 12 parts by weight of a lipid-regulating agent
in a syrupy form, prepared by the method of Example A-2, 50 parts
by weight of starchy syrup, 122 parts by weight of "TREHA.RTM.",
.alpha.,.alpha.-trehalose commercialized by Hayashibara Shoji Inc.,
Okayama, Japan, five parts by weight of pectin, three parts by
weight of 50% citric acid aqueous solution, and 27 parts by weight
of isomerized sugar were admixed with suitable amount of water and
dissolved. The resulting solution was gradually boiled down to give
a Brix value of about 78, put into a suitable mold, and cooled to
an ambient temperature to make into a hard jelly for regulating the
amount of lipids. Since CTS, its saccharide-derivative, and a
dietary fiber, pectin regulate the lipids in the living body, the
product can be preferably used for the purpose of diet and
preventing lifestyle-related disease or as a confectionary for
patients of lifestyle-related disease such as adiposis and
hyperlipemia, requiring the restriction of lipids intake. Further,
the product is a hard jelly having a good flavor with no
syneresis.
EXAMPLE B-11
Hard Candy for Regulating the Amount of Lipids
[0079] Sixty parts by weight of sucrose, 20 parts by weight of
"TREHA.RTM.", .alpha.,.alpha.-trehalose commercialized by
Hayashibara Shoji Inc., Okayama, Japan, and 1.5 parts by weight of
a mixture of amino acids were admixed with 85 parts by weight of
water, and then the resulting mixture was made into hard candy for
regulating the amount of lipids by the conventional method. Since
CTS and its saccharide-derivative regulate the lipids in the living
body, the product can be preferably used for the purpose of diet
and preventing lifestyle-related disease or as a confectionary for
patients of lifestyle-related disease such as adiposis and
hyperlipemia, requiring the restriction of lipids intake. Further,
since bitter taste of amino acids is reduced by
.alpha.,.alpha.-trehalose, CTS, and its saccharide-derivative, the
product is a tasty candy comprising amino acids.
EXAMPLE B-12
Rice Flour Bread for Regulating the Amount of Lipids
[0080] Four hundred parts by weight of "KOME-NO-KO (for bread)",
rice flour premixed with gluten, commercialized by Saito Seifun
Co., Ltd., Niigata, Japan, eight parts by weight of sodium
chloride, 40 parts by weight of a powdery lipid-regulating agent
comprising crystalline CTS pentahydrate as an effective ingredient,
prepared in Example A-3, 12 parts by weight of sucrose, 12 parts by
weight of skim milk, one part by weight of raw yeast, eight parts
by weight of pullulan, and 320 parts by weight of water were mixed
with stirring using a vertical mixer, and then 20 parts by weight
of butter was further added to the mixture and kneaded to make into
dough for bread. After fermenting the dough at 25.degree. C. for 50
minutes, the dough was divided into suitable pieces and resulting
doughs were kept at 35.degree. C. for 50 minutes under the humidity
conditions of 75%. Then, the fermented doughs were placed into a
oven and baked for 40 minutes in the oven in which the upper- and
lower temperature were controlled to 180.degree. C. to make into
rice bread for regulating the amount of lipids. Since the bread
comprises CTS, lipids in the living body can be regulated by taking
the product. Therefore, the product can be preferably used for the
purpose of diet, preventing lifestyle-related disease, or as a meal
for patients of lifestyle-related disease such as adiposis and
hyperlipemia, requiring the restriction of lipids intake. Further,
the product is delicious rice bread having a satisfactory flavor
and mouthfeel.
EXAMPLE B-13
Cooked Rice for Regulating the Amount of Lipids
[0081] Three hundred parts by weight of pre-washed and drained rice
was soaked into a solution, prepared by dissolving 13.5 parts by
weight of a powdery lipid-regulating agent which is prepared in
Example A-4 into 375 parts by weight of water, for one hour. Then,
the rice was cooked using a rice cooker to make into cooked rice
for regulating the amount of lipids. Since the cooked rice
comprises CTS, lipids in the living body can be regulated by taking
the product. Therefore, the product can be preferably used for the
purpose of diet, preventing, lifestyle-related disease, or as a
meal for patients of lifestyle-related disease such as adiposis and
hyperlipemia, requiring the restriction of lipids intake.
EXAMPLE B-14
Fish Paste for Regulating the Amount of Lipids
[0082] Two thousand parts by weight of fish meat of Alaska Pollock
which is presoaked in water, 105 parts by weight of a powdery
lipid-regulating agent, prepared by the method of Example A-5,
three parts by weight of sodium lactate, and 0.2 part by weight of
proanthocyanidin were mixed and the resulting mixture was minced
and frozen at -20.degree. C. to make into a frozen mince. After
preserving at -20.degree. C. for 90 days, the frozen mince was
thawed. To the thawed mince, 100 parts by weight of an aqueous
solution, prepared by dissolving 40 parts by weight of sodium
glutamate, 100 parts by weight of potato starch, three parts by
weight of sodium polyphosphate, 50 parts by weight of sodium
chloride, and five parts by weight of sorbitol into 150 parts by
weight of ice water, was added and the resulting mixture was mashed
to make into paste. The resulting paste was divided to about 120
grams each, and shaped on the board. The shaped fish paste was
steamed with taking 30 minutes to give an internal temperature of
about 80.degree. C. The steamed fish paste was cooled under the
ambient temperature and preserved at 4.degree. C. for 24 hours to
produce a fish paste for regulating the amount of lipids. Since CTS
and proanthocyanidin regulates the lipids in the living body, the
product can be preferably used for the purpose of diet and
preventing lifestyle-related disease, or as a food or its material
for patients of lifestyle-related disease such as adiposis and
hyperlipemia, requiring the restriction of lipids intake.
EXAMPLE B-15
Bacon for Regulating the Amount of Lipids
[0083] Twenty two parts by weight of sodium chloride, four parts by
weight of a lipid-regulating agent comprising crystalline CTS
pentahydrate, prepared by the method of Example A-3, one part by
weight of sucrose, two parts by weight of sodium lactate, two parts
by weight of sodium polyphosphate, 0.5 part by weight of ascorbic
acid, and 0.2 part by weight of sodium nitrite were admixed with
68.8 parts by weight of water and dissolved to make into a pickle
solution. Nine parts by weight of rib of hog was soaked with one
part by weight of the pickle solution uniformly with taking an
enough time. The resulting rib of hog was smoked by the
conventional method to make into bacon for regulating the amount of
lipids. After smoking, the bacon was preserved at an ambient
temperature for overnight and sliced. The resulting sliced bacon
was packed under vacuum and preserved at 10.degree. C. Since CTS
regulates the lipids in the living body, the product can be
preferably used for the purpose of diet and preventing
lifestyle-related disease, or as a food material for patients of
lifestyle-related disease such as adiposis and hyperlipemia,
requiring the restriction of lipids intake.
EXAMPLE B-16
Ice Cream for Regulating the Amount of Lipids
[0084] An ice cream was prepared by conventional method using 60
parts by weight of water, 12 parts by weight of non-fat milk, 12
parts by weight of sucrose, 5.5 parts by weight of "HALLODEX.TM.",
a saccharide composition comprising saccharide-derivatives of
.alpha.,.alpha.-trehalose commercialized by Hyayashibara Shoji
Inc., Okayama, Japan, 0.3 part by weight of gum, 0.5 part by weight
of vanilla extract, and 11 parts by weight of a powdery anhydrous
crystalline CTS prepared by the method of Example A-3. Since CTS
regulates the lipids in the living body, the product can be
preferably used for the purpose of diet and preventing
lifestyle-related disease or as an ice cream for patients of
lifestyle-related disease such as adiposis, hyperlipemia and
diabetes, requiring the restriction of lipids intake. Although the
product is produced without using fat (cream) which is usually used
for preparing ice cream, the product has a creamy mouthfeel and
taste similar with the case of a usual ice cream. Further, since
the ice cream does not contain fat, it is a low calorie ice cream
for regulating the amount of lipids.
EXAMPLE B-17
Salad Dressing for Regulating the Amount of Lipids
[0085] A salad dressing was prepared by conventional method using
40 parts by weight of water, 20 parts by weight of white vinegar,
15 parts by weight of vegetable oil, five parts by weight of
sucrose, two parts by weight of sodium chloride, one part by weight
of garlic powder, 0.5 part by weight of onion powder, 0.1 part by
weight of white pepper, 0.3 part by weight of gum and 15 parts by
weight of a lipid-regulating agent, a powdery crystalline CTS
pentahydrate prepared by the method of Example A-3. Since CTS
regulates the lipids in the living body, the product can be
preferably used for the purpose of diet and preventing
lifestyle-related disease or as a salad dressing for patients of
lifestyle-related disease such as adiposis, hyperlipemia and
diabetes, requiring the restriction of lipids intake. Although the
product is produced using about a half amount of vegetable oil
which is used in a usual salad dressing, the product has a
satisfactory mouthfeel and taste similar with the case of a usual
salad dressing. Further, since the product comprises CTS, it has a
characteristic of separating oil- and water-phases easily.
EXAMPLE B-18
Tablet for Regulating the Amount of Lipids
[0086] Two hundred parts by weight of .gamma.-oryzanol, 650 parts
by weight of a lipid-regulating agent comprising crystalline CTS
pentahydrate, prepared by the method of Example A-3, 50 parts by
weight of glucosyl-hesperidin, and two parts by weight of magnesium
stearate were mixed to homogeneity and the mixture was made into a
250 mg-tablet by the conventional method. Since .gamma.-oryzanol,
CTS, and glucosyl-hesperidin regulates the lipids in the living
body, the product can be preferably used as a lipid-regulating
agent for patients of adiposis, fatty liver and hyperlipemia.
EXAMPLE B-19
Mixed Feed for Regulating the Amount of Lipids
[0087] Thirty parts by weight of wheat bran, 35 parts by weight of
skim milk, 10 parts by weight of rice bran, 10 parts by weight of
lactosucrose high content powder, 10 parts by weight of a
multi-vitamin agent, five parts by weight of fish powder, five
parts by weight of calcium monohydrogen-phosphate, three parts by
weight of a liquid fat, three parts by weight of calcium carbonate,
one part by weight of glucosyl-rutin, two parts by weight of sodium
chloride, five parts by weight of a lipid-regulating agent in a
syrupy form, prepared by the method of Example A-2, and two parts
by weight of a mineral agent were mixed to make into a mixed feed
for regulating the amount of lipids. Since CTS, its
saccharide-derivative, and glucosyl-rutin regulates the lipids in
the living body, the product can be preferably used as a feed to
regulate lipids in the living body. The product is a feed or pet
food for domestic animals, poultry, and pets, and is particularly
preferable as a feed for pigs.
INDUSTRIAL APPLICABILITY
[0088] As described above, the present invention relates to a
lipid-regulating agent comprising CTS, a non-reducing saccharide
constructed by glucose, and/or its saccharide-derivative(s) as an
effective ingredient(s) and a composition for regulating the amount
of lipids comprising the lipid-regulating agent, where they can be
used for regulating the amount of lipids of animals including
human. Further, Since CTS and/or its saccharide-derivative(s) are
safe even when one intakes orally and have satisfactory stability,
the lipid-regulating agent comprising CTS and/or its
saccharide-derivative(s) as an effective ingredient(s) of the
present invention can be used in various fields such as foods and
beverages, cosmetics, medicated cosmetics, pharmaceuticals, etc.
The present invention, having these outstanding functions and
effects, is a significantly important invention that greatly
contributes to this art.
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