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STRAIN SHOWING LIVER FUNCTION IMPROVING ACTIVITY, AND USE
THEREOF
Technical Field
This application claims the priority benefit of Korean Patent Application No.
10-2019-
0056228 filed on May 14, 2019 and Korean Patent Application No. 10-2020-
0042863 filed on
April 8, 2020, the contents of each of which are incorporated herein by
reference in their
entirety.
The present invention relates to a strain having liver function improving
activity, and
a use thereof Specifically, the present invention relates to a health food
composition and a
pharmaceutical composition for improving liver function, using a Lactobacillus
pentosus KF8
(accession number KCCM11997P) strain, a Bacillus subtilis KF11 (accession
number
KCCM11981P) strain, or a Lactococcus lactis KF140 (accession number
KCCM11673P) strain.
Background Art
The liver is known to act on blood storage and circulation, blood volume
control and
defense detoxification in the human body, and is closely related to mental
activity. Our body is
always exposed to pollutants and toxic substances caused by industrialization,
so our liver is
constantly suffering from detoxification.
In addition, the liver is an organ with a large buffering capacity, and the
symptom does
not appear well in the early stages of the disease and is found only when it
is significantly
worsened. Liver cirrhosis, liver cancer and the like are common last steps
when various liver
diseases develop chronically. The causes include alcohol, drugs, chemicals,
viral hepatitis,
biliary tract disease, metabolic diseases such as hematochromatosis, and
autoimmune diseases,
but the cause of the liver diseases is often unknown. Therefore, the liver is
a very important
organ for early health management.
According to the investigation of the recent health level of Koreans, the
mortality rate
from liver cancer was 23.4 per 100,000 people, the highest in the world, and
the mortality rate
from chronic liver disease was also the third with 28.8 per 100,000 people. In
addition, the
Korean National Statistical Office recently announced that liver disease was
the highest cause
of death in Korea with 56.1 cases per 100,000 people in their 40s, and liver
disease is emerging
as an important social problem. In recent years, the number of liver damage
caused by mental
stress is also increasing, so more research is being focused on improving
liver function.
On the other hand, probiotics have been used in our diet for a long time, and
in
particular, beneficial effects such as intestinal regulating action,
anticancer effect, and immune
enhancing effect have been reported.
Accordingly, while studying the new physiological activity for the probiotics,
in
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particular, a Lactobacillus pentosus KF8 (accession number KCCM11997P) strain,
a Bacillus
subtilis KF11 (accession number KCCM11981P) strain, and a Lactococcus lactis
KF140
(accession number KCCM11673P) strain, which were isolated and identified by
the present
inventors as a new strain through previous studies, the present inventors
found that the above
bacteria can effectively improve liver function. Based on the above, the
present inventors
completed the present invention.
Prior Art Document
Patent Document
(Patent Document 1) Korean Patent Publication No. 10-2018-0103772
Detailed Description of the Invention
Technical Problem
Therefore, an object of the present invention is to provide a health food
composition
for improving liver function, which contains, as an active ingredient, one or
more strains
selected from the group consisting of a Lactobacillus pentosus KF8 (accession
number
KCCM11997P) strain, a Bacillus subtilis KF11 (accession number KCCM11981P)
strain, and
a Lactococcus lactis KF140 (accession number KCCM11673P) strain, a lysate
thereof or a
culture product thereof
In addition, another object of the present invention is to provide a
pharmaceutical
composition for improving liver function, which contains, as an active
ingredient, one or more
strains selected from the group consisting of a Lactobacillus pentosus KF8
(accession number
KCCM11997P) strain, a Bacillus subtilis KF11 (accession number KCCM11981P)
strain, and
a Lactococcus lactis KF140 (accession number KCCM11673P) strain, a lysate
thereof or a
culture product thereof
Solution to Problem
In order to achieve the above object of the present invention, the present
invention
provides a health food composition for improving liver function, which
contains, as an active
ingredient, one or more strains selected from the group consisting of a
Lactobacillus pentosus
KF8 (accession number KCCM11997P) strain, a Bacillus subtilis KF11 (accession
number
KCCM11981P) strain, and a Lactococcus lactis KF140 (accession number
KCCM11673P)
strain, a lysate thereof or a culture product thereof
In one embodiment of the present invention, the composition may inhibit the
activity
of alanine aminotransferase (ALT) or aspartate aminotransferase (AST), inhibit
an increase in
the concentration of total cholesterol or triglycerides in the liver, or
inhibit fat accumulation in
the liver.
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In one embodiment of the present invention, the health food composition may be
any
one formulation selected from powder, granules, pills, tablets, capsules,
candies, syrups and
beverages.
In addition, the present invention provides a pharmaceutical composition for
improving liver function, which contains, as an active ingredient, one or more
strains selected
from the group consisting of a Lactobacillus pentosus KF8 (accession number
KCCM11997P)
strain, a Bacillus subtilis KF11 (accession number KCCM11981P) strain, and a
Lactococcus
lactis KF140 (accession number KCCM11673P) strain, a lysate thereof or a
culture product
thereof
In one embodiment of the present invention, the composition may inhibit the
activity
of alanine aminotransferase (ALT) or aspartate aminotransferase (AST), inhibit
an increase in
the concentration of total cholesterol or triglycerides in the liver, or
inhibit fat accumulation in
the liver.
In addition, the present invention provides a method for improving liver
function,
comprising administering or taking to a subject a composition containing, as
an active
ingredient, one or more strains selected from the group consisting of a
Lactobacillus pentosus
KF8 (accession number KCCM11997P) strain, a Bacillus subtilis KF11 (accession
number
KCCM11981P) strain, and a Lactococcus lactis KF140 (accession number
KCCM11673P)
strain, a lysate thereof or a culture product thereof
In addition, the present invention provides use of a composition containing,
as an
active ingredient, one or more strains selected from the group consisting of a
Lactobacillus
pentosus KF8 (accession number KCCM11997P) strain, a Bacillus subtilis KF11
(accession
number KCCM11981P) strain, and a Lactococcus lactis KF140 (accession number
KCCM11673P) strain, a lysate thereof or a culture product thereof for
improving liver function.
Effects of the Invention
The present invention relates to a health food composition for improving liver
function
and a pharmaceutical composition for improving liver function, which contain,
as an active
ingredient, one or more strains selected from the group consisting of a
Lactobacillus pentosus
KF8 (accession number KCCM11997P) strain, a Bacillus subtilis KF11 (accession
number
KCCM11981P) strain, and a Lactococcus lactis KF140 (accession number
KCCM11673P)
strain, a lysate thereof or a culture product thereof The strain of the
present invention shows
excellent activity in inhibiting the activity of alanine aminotransferase
(ALT) or aspartate
aminotransferase (AST), inhibiting an increase in the concentration of total
cholesterol or
triglycerides in the liver, and inhibiting fat accumulation in the liver,
thereby being effectively
usable in the preparation of a food composition and a pharmaceutical
composition for
improving liver function.
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Brief Description of Drawings
Fig. 1 illustrates a photograph showing the form of health food for improving
liver
function, which is prepared using a Lactobacillus pentosus KF8 (accession
number
KCCM11997P) strain, a Bacillus subtilis KF11 (accession number KCCM11981P)
strain, and
a Lactococcus lactis KF140 (accession number KCCM11673P) strain in one
embodiment of
the present invention.
Best Mode for Carrying out the Invention
The present invention relates to a novel use of a strain having liver function
improving
activity, wherein the strain having liver function improving activity is a
Lactobacillus pentosus
KF8 (accession number KCCM11997P) strain, a Bacillus subtilis KF11 (accession
number
KCCM11981P) strain, and a Lactococcus lactis KF140 (accession number
KCCM11673P)
strain, which were first isolated and identified by the inventors of the
present invention and
published previously.
The present inventors performed an experiment in order to determine whether
the
strain of the present invention can improve liver function and have liver
protecting activity. As
a result, it was found that as a result of administering the food form
prepared by pulverizing
the strain to an animal model for liver damage, the effect of protecting liver
cells and inhibiting
the activity of ALT and AST, which are indicators of liver damage, was
excellent.
The ALT (aspartate aminotransferase), which is a representative liver damage
indicator,
is an enzyme present in the liver, kidney, heart, muscle, and the like, and is
present in the largest
amount in the liver. The ALT is used as an indicator of liver disease because
it reacts sensitively
when liver cells are damaged and the level is increased. When the liver is
damaged for a variety
of reasons, it is mainly released into the blood and the blood level is
elevated.
In addition, AST (alanine aminotransferase), which is another liver damage
indicator,
is also released into the blood during liver damage, and the blood level is
elevated compared
to the normal condition. Therefore, the level of liver damage can be confirmed
by measuring
the content of these indicators.
On the other hand, as a result of administering a Lactobacillus pentosus KF8
(accession
number KCCM11997P) strain, a Bacillus subtilis KF11 (accession number
KCCM11981P)
strain, or a Lactococcus lactis KF140 (accession number KCCM11673P) strain,
which is the
strain of the present invention, to a mouse group in which liver damage is
induced, it was found
that it had an effect of reducing the increased ALT and AST levels in the
blood by two times or
more.
In addition, in one embodiment of the present invention, it was analyzed
whether the
content of total cholesterol and triglycerides increased in the liver
according to the onset of
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fatty liver could be reduced when the strain of the present invention was
administered. As a
result of administering the strain of the present invention to a fatty liver
animal model, it was
found that the contents of total cholesterol and triglycerides in the liver
were effectively
inhibited, and it was found that fat accumulation in the liver was inhibited.
It is known that fatty liver is caused by inhibition of the formation and
release of
lipoproteins in the liver or by enhancement of triglyceride synthesis.
Ethionine inhibits the
synthesis of RNA and protein and reduces the production of ATP in the liver,
thereby inhibiting
the excretion of triglycerides into the plasma, and also inhibits the
synthesis of lipoproteins,
thereby inhibiting the release of lipids from the liver. Since the release is
inhibited, triglycerides
are accumulated in the liver tissue when ethionine is administered, and the
amount of
triglycerides and total cholesterol in the blood is rapidly lowered, causing
microvesicular
steatosis. Therefore, in the ethionine-induced fatty liver model, the
triglyceride content in the
liver tissue and the total cholesterol content in the serum are used as
indicators of the model.
In this regard, it can be seen that the strain of the present invention is
useful for
improving and treating fatty liver because it has been confirmed that it has
an effect of reducing
triglycerides and total cholesterol in liver tissue.
Furthermore, in another embodiment of the present invention, as a result of
performing
a clinical trial on volunteers conducted in accordance with the regulations of
the Institutional
Review Board (IRB), it was found that in the case of the group who ingested
the health food
prepared using the strain of the present invention, the activity of ALT and
AST in the blood
was inhibited compared to the group who did not ingest the same, thereby
having an effect of
improving liver function, and it was found that the contents of total
cholesterol and LDL
cholesterol were also reduced by ingestion of the strain of the present
invention.
Therefore, through these results, the present inventors found that a
Lactobacillus
pentosus KF8 (accession number KCCM11997P) strain, a Bacillus subtilis KF11
(accession
number KCCM11981P) strain, or a Lactococcus lactis KF140 (accession number
KCCM11673P) strain, which was first isolated and identified by the present
inventors, can be
used for the purpose of improving liver function.
Therefore, the present invention may provide a health food composition for
improving
liver function, which contains, as an active ingredient, one or more strains
selected from the
group consisting of a Lactobacillus pentosus KF8 (accession number KCCM11997P)
strain, a
Bacillus subtilis KF11 (accession number KCCM11981P) strain, and a Lactococcus
lactis
KF140 (accession number KCCM11673P) strain, a lysate thereof or a culture
product thereof
The number of the above strains that may be contained in the health food
composition
for improving liver function of the present invention may be 1.0 x105 CFU/g to
2.0 x 1015 CFU/g,
and the health food composition of the present invention may include one type
of strain among
the above strains, or may include one or more types of mixed strains, and most
preferably, it
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may include mixed strains in which all three types of strains are mixed.
The effect of improving liver function of the Lactobacillus pentosus KF8
(accession
number KCCM11997P) strain, the Bacillus subtilis KF11 (accession number
KCCM11981P)
strain, or the Lactococcus lactis KF140 (accession number KCCM11673P) strain
investigated
in the experiment of the present invention, i.e., the effects of inhibiting
the activity of ALT and
AST in the blood, inhibiting total cholesterol or triglycerides in the liver
tissue, and inhibiting
fat accumulation in the liver, can also be induced by the treatment with the
single strain alone,
and when two or more strains are mixed, a better effect can be exhibited, and
when all three
strains are mixed, the best effect can be exhibited.
The food composition of the present invention includes all forms of a
functional food,
a nutritional supplement, a health food, a food additive, and the like. The
food composition of
the above type may be manufactured in various forms according to the
conventional methods
known in the art. For example, as a health food, at least one of the group of
the strains of the
present invention itself, a lysate thereof, and a culture product of the above
strain may be
drunken in the form of tea, juice, and drink, and may be ingested by
granulation, encapsulation,
and pulverization. In addition, at least one of the group of the strains of
the present invention,
a lysate thereof, and a culture product thereof may be manufactured in the
form of a
composition by mixing with a known substance or an active ingredient known to
have an effect
of improving liver function. In addition, a functional food may be
manufactured by adding at
least one of the group of the strains of the present invention, a lysate
thereof, and a culture
product thereof to beverages (including alcoholic beverages), fruits and their
processed foods
(for example, a canned fruit, a bottled fruit, jam, marmalade, etc.), fish,
meat, and its processed
food (for example, ham, sausage corned beef, etc.), breads and noodles (for
example, udon,
buckwheat noodle, ramen, spaghetti, macaroni, etc.), fruit juice, various
drinks, cookies, taffy,
dairy products (for example, butter, cheese, etc.), edible vegetable oil and
fat, margarine,
vegetable protein, retort food, frozen food, various seasonings (for example,
bean paste, soy
sauce, sauce, etc.), and the like.
The preferable content of the strain of the present invention, a lysate
thereof, and a
culture product thereof, etc. in the food composition of the present invention
is preferably, but
not limited to, 0.01 to 50 wt% in a finally manufactured food. In addition, in
order to use in the
form of a food additive, the strain of the present invention, a lysate thereof
or a culture product
thereof as an active ingredient may be manufactured in the form of powder or
concentrate.
In addition, the present invention may provide a pharmaceutical composition
for
improving liver function, which contains, as an active ingredient, one or more
strains selected
from the group consisting of a Lactobacillus pentosus KF8 (accession number
KCCM11997P)
strain, a Bacillus subtilis KF11 (accession number KCCM11981P) strain, and a
Lactococcus
lactis KF140 (accession number KCCM11673P) strain, a lysate thereof or a
culture product
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thereof
The pharmaceutical composition may contain a pharmaceutically acceptable salt
alone
or may further contain one or more pharmaceutically acceptable carriers,
excipients, or diluents.
The pharmaceutically acceptable carrier may further include, for example, a
carrier for oral
administration or a carrier for parenteral administration. Carriers for oral
administration may
include lactose, starch, cellulose derivatives, magnesium stearate, stearic
acid, and the like. In
addition, carriers for parenteral administration may include water, a suitable
oil, saline, aqueous
glucose, glycol, and the like, and may further include a stabilizer and a
preservative. Suitable
stabilizers include antioxidants such as sodium hydrogen sulfite, sodium
sulfite or ascorbic
acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-
paraben and
chlorobutanol. As other pharmaceutically acceptable carriers, reference may be
made to those
described in the literature (Remington's Pharmaceutical Sciences, 19th ed.,
Mack Publishing
Company, Easton, PA, 1995).
The pharmaceutical composition of the present invention may be administered by
any
method to a mammal including a human. For example, it may be administered
orally or
parenterally. A parenteral administration method includes intravenous,
intramuscular,
intraarterial, intramedullary, intrathecal, intracardiac, transdermal,
subcutaneous,
intraperitoneal, intranasal, intestinal, topical, sublingual, or intracolonic
administration, but is
not limited thereto. Preferably, the pharmaceutical composition of the present
invention may
be administered orally or transdermally.
The pharmaceutical composition of the present invention may be formulated in a
formulation for oral administration or a formulation for parenteral
administration by the routes
of administration as described above.
In the case of a formulation for oral administration, the composition of the
present
invention may be formulated using the methods known in the art into powder,
granules, tablets,
pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and
the like. For example,
a formulation for oral administration may be obtained as a tablet or a dragee
by blending an
active ingredient with a solid excipient, milling them, adding a suitable
adjuvant, and then,
processing into a granule mixture. Examples of suitable excipients may include
sugars, such as
lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol,
and the like, starches,
such as corn starch, wheat starch, rice starch, potato starch, and the like,
celluloses, such as
cellulose, methyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl
methylcellulose,
and the like, and fillers, such as gelatin, polyvinylpyrrolidone, etc. In
addition, in some cases,
cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate,
etc. may be added as
a disintegrating agent. Furthermore, the pharmaceutical composition of the
present invention
may further comprise anticoagulants, lubricants, wetting agents, flavoring
agents, emulsifiers,
preservatives, and the like.
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The formulation for parenteral administration may be formulated in the form of
injections, creams, lotions, external ointments, oils, moisturizers, gels,
aerosols, and nasal
inhalers using the methods known in the art. These formulations are described
in the literature
(Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing
Company, Easton,
Pennsylvania 18042, Chapter 87: Blaug, Seymour), which is a formulary
generally known in
all pharmaceuticals and chemistry.
The total effective amount of the strain of the present invention itself, a
lysate thereof,
and a culture product of the above strain, etc., may be administered to a
patient as a single dose,
and may be administered by fractionated treatment protocol, that is a long-
term administration
of multiple doses. The content of the active ingredient in the pharmaceutical
composition of
the present invention may vary depending on the severity of the disease. The
preferable total
dose of the strain of the present invention, a lysate thereof, and a culture
product thereof may
be preferably about 0.01 ug to 1,000 mg, most preferably 0.1 ug to 100 mg, per
1 kg of patient's
body weight per day. However, the dose of the strain of the present invention
itself, a lysate
thereof, and a culture product of the above strain, etc., is determined upon
consideration of
routes of administration of the pharmaceutical composition and the number of
times being
treated, as well as various factors, such as patient's age, body weight,
health condition, sex,
severity of diseases, diet, excretion rate, and the like, for determining the
effective dose for the
patient. Thus, upon consideration of such aspects, a person having ordinary
skill in the art
would be able to determine an appropriate effective dose according to the
certain use of the
strain of the present invention, a lysate thereof, and a culture product
thereof as an immune
function enhancer. The pharmaceutical composition according to the present
invention is not
particularly limited to the formulations, routes of administration, and
administration methods
as long as the effect of the present invention shows.
Furthermore, in the present invention, improvement of liver function refers to
treatment, alleviation, and prevention of symptoms caused by liver damage, and
means to treat,
alleviate or prevent liver function, liver condition, liver disease, and liver
disorder.
In the present invention, liver disease that can be caused by liver damage may
include
autoimmune liver disease, drug-induced liver disease, alcoholic liver disease,
infectious liver
disease, congenital metabolic liver disease, acute liver disease, hepatitis,
bile stasis, fatty liver
and chronic liver disease, but is not limited thereto.
Hereinafter, the present invention will be described in more detail through
the
examples. These examples are for illustrating the present invention in more
detail, and the
scope of the present invention is not limited to these examples.
<Preparation Example>
<1> Preparation of test food containin2 the strain of the present invention
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The present inventors requested a strain depositary authority to assign an
accession
number for three strains previously isolated and identified as new novel
strains, and requested
Mediogen Co., Ltd. to prepare the test food using a total of three strains
deposited
(Lactobacillus pentosus KF8, Bacillus subtilis KF11, and Lactococcus lactis
KF140).
A total of three strains used in the present invention are as follows.
- Lactobacillus pentosus KF8: a strain that was deposited on March 24, 2017
at the
Korean Culture Center of Microorganisms (KCCM), which is an international
microorganism
depositary authority, and assigned with an accession number KCCM 11997P was
used.
- Bacillus subtilis KF11: a strain that was deposited on February 24, 2017
at the Korean
Culture Center of Microorganisms (KCCM), which is an international
microorganism
depositary authority, and assigned with an accession number KCCM 11981P was
used.
- Lactococcus lactis KF140: a strain that was deposited at the Korean
Culture Center
of Microorganisms (KCCM), which is an international microorganism depositary
authority,
and assigned with an accession number KCCM 11673P was used.
Preparation of test foods using these strains was requested to Mediogen Co.,
Ltd. and
prepared according to the conventional method for producing strain-type
products. The main
raw materials, including maltodextrin, anhydrous crystalline glucose, and each
of the three
strains of the present invention (2.0 x 109 CFU/g), were packaged in a unit of
1.5 g per package
and kept refrigerated until used for the test.
At this time, each of the strains used for the preparation of the test food
was cultured
in a culture medium to obtain a strain, and then it was lyophilized and
pulverized to obtain the
strain in the form of a powder and use it.
A photograph of the test food prepared for use in the present invention is
shown in Fig.
1.
<2> Test subject
In order to confirm the effect of improving liver function on the three
strains of the
present invention, the test subjects were selected as follows.
Subjects were selected as those who met the criteria below, and they
volunteered to
recruit subjects for human application tests, and the following experiment was
conducted for
only those who passed the selection criteria. A screening test was conducted
for a total of 44
adults, aged 25 to 45 years of age, residing in Daegu and Gyeongbuk area, and
36 people who
met the selection criteria and did not meet the exclusion criteria were
selected as subjects.
Subject selection criteria were limited to those who were able to follow-up
during the
trial period, and those who voluntarily signed the consent form after fully
explaining the
purpose and content of the study.
On the other hand, those who met the following conditions were excluded.
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= Those who have experience of hypersensitivity reaction when ingesting
strain
products
= Those who have ingested prescription drugs, over-the-counter drugs,
health
functional foods, or probiotics within the past month
= Those who have ingested antibiotics within 1 month of participating in
the test
= Those who have undergone endoscopic examination of stomach or large
intestine
within 1 month of participating in the test
= Those who have a BMI of less than 20 or greater than 35
= Those who have high blood pressure (systolic blood pressure of 160 mmHg
or
diastolic blood pressure of 100 mmHg or higher)
= Those who have a fasting blood glucose concentration of greater than 110
= Those who have ALT or AST exceeding 2 times the upper limit of normal
= Women who are pregnant or lactating
= Women of childbearing age who do not consent to contraception using
medically
proven methods (e.g., condoms, loops, femidoms, etc.) during the test period
= Those who need continuous treatment for anorexia, depression, bipolar
disorder,
psychiatric disease, etc.
= Those who have systemic diseases such as immune-related diseases, severe
liver or
kidney failure, malignant tumors, lung diseases, collagenosis, multiple
sclerosis, allergic skin
diseases, and other autoimmune diseases
= Those who have a history of gastrointestinal disease or gastrointestinal
surgery
(excluding simple appendectomy or hernia surgery) that may affect the
absorption of the test
food
= Those who have participated in other human application tests or clinical
trials within
3 months of participating in the test and have ingested the test product
(excluding cosmetics
human application tests)
= Those who are judged to be difficult to conduct the test in the judgment
of the
researcher other than the above
In addition, subjects who met the following conditions were excluded from this
test
due to the questionnaire on the day of hospitalization.
= Those who have ingested alcohol in excess of 50 g (one or more bottle of
soju or two
or more bottles of beer) per serving within 2 weeks before hospitalization
= Those who have consumed more than 1 glass of soju or 1 glass of beer per
day within
1 week before hospitalization
= Those who have ingested dairy products, fast foods such as hamburgers and
pizzas,
instant foods, fried foods, grilled foods, etc. within 1 week before
hospitalization
= Those who have ingested antibiotics after the date of previous visit
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= Those who have undergone endoscopic examination of stomach or large
intestine
after the date of previous visit
= Those who have taken prescription drugs, over-the-counter drugs, or
health
functional foods after the date of the previous visit
Subjects selected under these conditions were set to be 10 people per
experimental
group as the minimum number of subjects that could be analyzed for
effectiveness.
The clinical trials of the selected subjects were conducted according to the
regulations
of the Institutional Review Board (IRB).
<Example 1>
Analysis of the effect of improvin2 liver function accordin2 to in2estion of
the
strain of the present invention
Changes in AST, ALT, total cholesterol, triglyceride, LDL cholesterol, and HDL
cholesterol in the blood were measured using blood collected before and after
ingestion of each
strain for 26 days for the test subjects.
[Table 1]
Result of analysis of components in the blood
lime Before ingestion ' After ingestion
0.8 17.30 6.06 20.10 14.31
AST(V4:T) 1,:q1 20.0931,-.6:83 1618:0.60
KE 19. 30 7,39 15.60 4.01
KF3 31.101-14.04 113.10 9.17
ALrom K17-11 29.00 12.18 14.55 6.17
KF1-710 31.30 19.74 18.50 13.79
KF2 170.90 33.44 169 00 28.1.8.
Ch01 este
[^,,E 16991 t26-.6,5 167 00 2832
total
.1=1.15=11MIMIM
162 00 24.1. 158.20 19.34
KFl3 12110 1:77-92 3.23.60t, 5215
Trigilyceride 11 90.09 100.35 103.09 54 46
84,70 41.1614 107.60 22.23
KFa rig :,)0 22. 108,70,t21 33
(301estero1 11109 t20 32 104 09 .28.09
*140 115.70 17,99 6.$ 16239
50.10 13.72 45.80 9.26
Kni 57.64 113 53.55.t12.02
0701eUerol
0140 46.90.1:1037 48.30 12.02
As a result of the analysis, as shown in Table 1 above, it was found that in
the group
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that ingested each of the strains of the present invention, Lactobacillus
pentosus KF8, Bacillus
subtilis KF11, and Lactococcus lactis KF140, the levels of alanine
aminotransferase (ALT) and
aspartate aminotransferase (AST), indicators of liver function were
effectively inhibited
compared to those before ingestion of the strain.
Therefore, through these results, the present inventors found that the strains
of
Lactobacillus pentosus KF8, Bacillus subtilis KF11, and Lactococcus lactis
KF140 can be used
for the purpose of improving liver function and preventing and treating liver
disease.
<Example 2>
Analysis of the effect of improvin2 liver function accordin2 to in2estion of
the
strain of the present invention in a liver dama2e-induced animal model
As experimental animals, male SD (Sprague-Dawley) rats (SLC, Japan) having a
body
weight of 200 g were used, and 5 animals were distributed to each experimental
group and used
for the experiment. Each experimental group is as follows.
[Table 2]
Content of administration
Normal group ingestion of normal diet
Control group normal diet + intraperitoneal administration of carbon
tetrachloride
Experimental normal diet + intraperitoneal administration of carbon
tetrachloride +
group 1 administration of Lactobacillus pentosus KF8
Experimental normal diet + intraperitoneal administration of carbon
tetrachloride +
group 2 administration of Bacillus subtilis KF11
Experimental normal diet + intraperitoneal administration of carbon
tetrachloride +
group 3 administration of Lactococcus lactis KF140
At this time, the carbon tetrachloride was intraperitoneally administered
twice a week
for 4 weeks at a dose of 0.75 ml/kg to the rat as a 50% solution mixed with
corn oil. 50 mg/kg
of each of the functional powder food containing the strain of the present
invention prepared
in Preparation Example was suspended in a 1% CMC solution and orally
administered once a
day, 6 times a week to the experimental groups. Thereafter, the administration
was continued
for 4 weeks, and then the animals were sacrificed to obtain the serum. In
order to examine the
therapeutic effect of the strain of the present invention on the liver damage
induced by carbon
tetrachloride, the activity of ALT and AST was measured.
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[Table 3]
Result of measurement of ALT and AST concentration
ALT (U/T) AST (U/T)
Normal group 70 10 85 22
Control group 182 12 200 42
Experimental group 1 (KF8) 92 21 100 13
Experimental group 2 (KF11) 87 17 98 21
Experimental group 3 (KF140) 89 22 96 35
As a result of the analysis, as shown in Table 3 above, it was found that in
the mouse
group that ingested the strain of the present invention, the elevated ALT and
AST in the serum
due to carbon tetrachloride were effectively inhibited.
These results indicate that the Lactobacillus pentosus KF8, Bacillus subtilis
KF11 and
Lactococcus lactis KF140 strains of the present invention have excellent
hepatoprotective
effects against hepatotoxicity and liver function effects.
<Example 3>
Analysis of the improvement effect accordin2 to in2estion of the strain of the
present invention in a fatty liver animal model
As experimental animals, male C57BL/6 mice (Central, Korea) having a body
weight
of 20 g were used, and 9 animals were distributed to each experimental group
and used for the
experiment. Each experimental group is as follows. A high fat diet (40% fat)
was provided in
pellet form as a fatty liver inducing substance, and the CML reaction product
was orally
administered daily at a dose of 10 mg/kg. Thereafter, the strain of the
present invention was
administered to each mouse, and then the degree of improvement of fatty liver
was analyzed.
[Table 4]
Content of administration
Normal group ingestion of normal diet
Control group high fat diet + CML diet
Experimental .
high fat diet + CML diet + administration of Lactobacillus pentosus KF8
group 1
Experimental .
high fat diet + CML diet + administration of Bacillus subtilis KF11
group 2
Experimental .
high fat diet + CML diet + administration of Lactococcus lactis KF140
group 3
At this time, 1x107 CFU of each of the strains of the present invention was
suspended
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in a 0.9% saline solution and orally administered once a day, 6 times a week
to the experimental
groups. Thereafter, the administration was continued for 4 weeks, and then the
animals were
sacrificed to collect the blood, and then the contents of liver function-
related enzymes and
triglycerides were measured.
[Table 5]
Result of measurement of concentration of liver function-related enzymes and
triglycerides
AST (U/L) ALT (U/L) Triglyceride (mg/g)
Normal group 44.5 1.7 19.7 1.1 62.3 7.2
Control group 64.2 1.2 31.2 2.0 85.5 7.2
Experimental group 1 (KF8) 48.4 2.6 24.4 2.8 68.4 5.0
Experimental group 2 (KF11) 48.6 3.4 27.5 1.6 66.3 7.4
Experimental group 3 (KF140) 43.1 2.5 24.3 1.7 59.5 6.8
As a result of the analysis, as shown in Table 5 above, it was found that in
the mouse
group that ingested the strain of the present invention, the levels of AST and
ALT increased by
liver damage were significantly inhibited, and an effect of preventing an
increase in the content
of triglycerides in the same manner was confirmed.
Through these results, the present inventors found that the Lactobacillus
pentosus KF8,
Bacillus subtilis KF11 or Lactococcus lactis KF140 strain of the present
invention can be
effective in preventing liver damage caused by glycotoxin ingestion, thereby
improving and
treating liver diseases such as fatty liver.
As described above, the present invention has been described mainly based upon
the
preferable examples. A person having ordinary skill in the art to which the
present invention
belongs would be able to understand that the present invention may be
implemented in a
modified form within the scope which does not deviate from the essential
characteristics of the
present invention. Therefore, the examples disclosed above should be
considered from an
explanatory point of view, not a limited point of view. The scope of the
present invention is
defined by the claims, not the foregoing description, and all of the
differences within the scope
equivalent thereto should be interpreted to be included in the scope of the
present invention.
[Accession number]
Depositary authority name: Korean Culture Center of Microorganisms (foreign
country)
Accession number: KCCM11997P
Deposit date: March 24, 2017
Depositary authority name: Korean Culture Center of Microorganisms (foreign
country)
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Accession number: KCCM11981P
Deposit date: February 24, 2017
Depositary authority name: Korean Culture Center of Microorganisms (foreign
country)
Accession number: KCCM11673P
Deposit date: March 6, 2015
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