U.S. patent application number 16/232747 was filed with the patent office on 2019-05-02 for composition for improving or preventing nonalcoholic fatty liver.
This patent application is currently assigned to KOHJIN LIFE SCIENCES CO., LTD.. The applicant listed for this patent is KOHJIN LIFE SCIENCES CO., LTD., KYOTO PREFECTURAL PUBLIC UNIVERSITY CORPORATION, PUBLIC UNIVERSITY CORPORATION YOKOHAMA CITY UNIVERSITY, SAGA UNIVERSITY. Invention is credited to Yuichiro EGUCHI, Takaomi KESSOKU, Atsushi NAKAJIMA, Susumu SAITO, Yusuke SAUCHI, Yoshio SUMIDA.
Application Number | 20190125822 16/232747 |
Document ID | / |
Family ID | 56848248 |
Filed Date | 2019-05-02 |
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United States Patent
Application |
20190125822 |
Kind Code |
A1 |
KESSOKU; Takaomi ; et
al. |
May 2, 2019 |
COMPOSITION FOR IMPROVING OR PREVENTING NONALCOHOLIC FATTY
LIVER
Abstract
An object of the present invention is to provide a composition
for preventing or improving fat deposition on the liver in spite of
the alcohol intake history of a level that a liver disease is not
caused. The inventors found that glutathione has an effect of
preventing or improving fat deposition on the liver, which is not
caused by alcohol, and completed the present invention. Among
nonalcoholic fat diseases, the present invention is particularly
effective in an early stage of the treatment or in a case where
treatment for another disease is not performed.
Inventors: |
KESSOKU; Takaomi;
(Yokohama-shi, JP) ; NAKAJIMA; Atsushi;
(Yokohama-shi, JP) ; SUMIDA; Yoshio; (Kyoto-shi,
JP) ; EGUCHI; Yuichiro; (Saga-shi, JP) ;
SAITO; Susumu; (Chiyoda-ku, JP) ; SAUCHI; Yusuke;
(Chiyoda-ku, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
KOHJIN LIFE SCIENCES CO., LTD.
PUBLIC UNIVERSITY CORPORATION YOKOHAMA CITY UNIVERSITY
KYOTO PREFECTURAL PUBLIC UNIVERSITY CORPORATION
SAGA UNIVERSITY |
Tokyo
Yokohama-shi
Kyoto-Shi
Saga-shi |
|
JP
JP
JP
JP |
|
|
Assignee: |
KOHJIN LIFE SCIENCES CO.,
LTD.
Tokyo
JP
PUBLIC UNIVERSITY CORPORATION YOKOHAMA CITY UNIVERSITY
Yokohama-shi
JP
KYOTO PREFECTURAL PUBLIC UNIVERSITY CORPORATION
Kyoto-shi
JP
SAGA UNIVERSITY
Saga-shi
JP
|
Family ID: |
56848248 |
Appl. No.: |
16/232747 |
Filed: |
December 26, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15555901 |
Sep 5, 2017 |
|
|
|
PCT/JP2016/056341 |
Mar 2, 2016 |
|
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16232747 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 1/16 20180101; A61K
38/00 20130101; A61K 38/063 20130101 |
International
Class: |
A61K 38/06 20060101
A61K038/06; A61K 38/00 20060101 A61K038/00; A61P 1/16 20060101
A61P001/16 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 3, 2015 |
JP |
2015-041317 |
Claims
1. A method for improving or preventing a nonalcoholic fatty liver
disease, comprising administering to a patient in need of treatment
for nonalcoholic fatty liver disease a composition comprising
glutathione as an active ingredient, wherein the patient in need of
treatment is diagnosed with nonalcoholic fatty liver disease
only.
2. A method for improving or preventing a nonalcoholic fatty liver
disease, comprising administering to a patient in need of treatment
for nonalcoholic fatty liver disease a composition comprising
glutathione as an active ingredient, wherein the nonalcoholic fatty
liver disease is a disease not complicated with diabetes.
3. A method for improving or preventing a nonalcoholic fatty liver
disease, comprising administering to a patient in need of treatment
for nonalcoholic fatty liver disease a composition comprising
glutathione as an active ingredient, wherein the nonalcoholic fatty
liver disease is a disease having low liver stiffness, and the
disease having low liver stiffness is a disease corresponding to
any one of the following: (1) Measurement value of Type IV collagen
(Type IV collagen 7S domain) in the serum is 4.5 ng/ml or less, or
(2) Measurement value with FibroScan (manufactured by Echo-Sense
Inc.), of which the principle is transient elastography that
measures the propagation velocity of pulse oscillatory wave in the
tissue with elasticity (kPa) by an ultrasonic pictorial analysis
method as a noninvasive examination, is 9.0 kPa or less.
4. A method for improving or preventing a nonalcoholic fatty liver
disease, comprising administering to a patient in need of treatment
for nonalcoholic fatty liver disease a composition comprising
glutathione as an active ingredient, wherein the nonalcoholic fatty
liver disease is a disease having a glycosylated hemoglobin (HbA1c)
of 6.5% or less.
Description
[0001] This application is a divisional application of U.S. patent
Ser. No. 15/555,901, filed Sep. 5, 2017, which is a U.S. national
stage entry of PCT/JP2016/056341, filed Mar. 2, 2016, which claims
priority to JP 2015-041317, filed Mar. 3, 2015. The disclosures of
each of the above are hereby incorporated by reference in their
entirety.
TECHNICAL FIELD
[0002] The present invention relates to a composition for
preventing or improving nonalcoholic fatty liver in which fat is
deposited on a liver in spite of the alcohol intake history of a
level that a liver disease is not caused.
BACKGROUND ART
[0003] Increase of diabetes, fatty liver, cancer, cardiac disease
and the like as a lifestyle related disease has been problematic.
Fat may be deposited on the liver and cause a hepatic disorder in
spite of the alcohol intake history of a level that a liver disease
is not caused. The cause is obesity, diabetes, hyperlipidemia or
the like, but factors involved in the pathogenesis are diverse and
there is no established therapy. The disease state of such
nonalcoholic fatty liver disease (NAFLD) may proceed to the
nonalcoholic steatohepatitis (NASH), hepatic cirrhosis or liver
cancer. The nonalcoholic fatty liver disease often comes with
insulin resistance, obesity, diabetes and hyperlipidemia. With
respect to the nonalcoholic fatty liver disease, exercise or
dietetic therapy is usually performed. In addition, with respect to
the nonalcoholic fatty liver disease, treatment with a medicament
or dietetic therapy using nutritional supplementary food or the
like is required in addition to exercise, dietetic therapy and the
like. Furthermore, nonalcoholic steatohepatitis is likely to
develop to hepatic cirrhosis or liver cell cancer, and thus needs
more active treatment and the like.
[0004] In a nonalcoholic fatty disease, treatment for diabetes and
the like may be performed together, and thus it is also necessary
to improve the nonalcoholic fatty liver disease while not
inhibiting treatment of the complication.
[0005] Therefore, functional food, supplement and the like having
therapeutic effects for the nonalcoholic fatty liver disease are
also desired, which have superior effects without concern of the
side reactions, and are easy to take, and can be taken for a long
time.
[0006] On the other hand, glutathione is a tripeptide consisting of
amino acids of cysteine, glutamic acid and glycine, and is known as
a drug improving detoxication of the liver.
[0007] However, it has been not known that glutathione is effective
for the nonalcoholic fatty liver disease.
CITATION LIST
Patent Literature
[0008] Patent Literature 1: WO 2009/096455 A
[0009] Patent Literature 2: JP 2006-199708 A
SUMMARY OF INVENTION
Technical Problem
[0010] An object of the present invention is to provide a
composition for preventing or improving fat deposition on the liver
in spite of the alcohol intake history of a level that a liver
disease is not caused.
Solution to Problem
[0011] The present inventors found that glutathione has an effect
of preventing or improving fat deposition on the liver, which is
not caused by alcohol, and completed the present invention.
[0012] The present inventions are as follows:
[0013] (1) A composition for improving a nonalcoholic fatty liver
disease, including glutathione as an active ingredient;
[0014] (2) A composition for preventing a nonalcoholic fatty liver
disease, including glutathione as an active ingredient;
[0015] (3) The composition according to (1) or (2), wherein the
nonalcoholic fatty liver disease is a disease developed with
nonalcoholic fatty liver only;
[0016] (4) The composition according to (1) or (2), wherein the
nonalcoholic fatty liver disease is a disease not complicated with
diabetes;
[0017] (5) The composition according to (1) or (2), wherein the
nonalcoholic fatty liver disease is a disease having low liver
stiffness; and
[0018] (6) The composition according to (1) or (2), wherein the
nonalcoholic fatty liver disease is a disease having a glycosylated
hemoglobin (HbA1c) of 6.5% or less.
Advantageous Effects of Invention
[0019] The composition of the present invention can be used
effectively in order to improve fatty liver by reducing fat
deposition on the liver with respect to nonalcoholic fatty liver,
and further can suppress development to hepatic disorder.
Therefore, the agent for suppressing fat deposition on the liver,
and the agent for improving fatty liver of the present invention
further have actions of preventing or improving development to
hepatic cirrhosis, hepatitis and liver cancer based on the actions
described above.
[0020] The composition of the present invention can be used
effectively for a patient who is in an early stage of nonalcoholic
fatty liver, particularly who is in mild disease state or does not
have a metabolic disorder such as high blood pressure,
hyperlipidemia or impaired glucose tolerance, a patient who has low
liver stiffness, and a patient who does not have disease other than
fatty liver. In these cases, the present invention is also
effective for a disease that is not affected with meal, exercise
therapy and the like.
DESCRIPTION OF EMBODIMENTS
[0021] Hereinafter, the present invention will be described in
detail.
[0022] The nonalcoholic fatty liver disease (NAFLD) in the present
invention means a disease leading to a hepatic disorder due to
abnormal buildup of fat in a liver cell in spite of the alcohol
intake history of a level that a liver disease is not caused, and a
condition of likely leading to such hepatic disorder, and includes
nonalcoholic simple fatty liver and nonalcoholic steatohepatitis.
Generally, the nonalcoholic fatty liver disease (NAFLD) in the
present invention represents the disease state where fat is
deposited in a liver cell and a hepatic disorder is caused in spite
of 20 g or less of the alcohol intake amount per one day.
[0023] Improvement of nonalcoholic fatty liver in the present
invention indicates no deterioration of the liver function. In
addition, improvement of nonalcoholic fatty liver in the present
invention indicates therapeutic effects for a disease such as acute
hepatitis, liver failure, chronic hepatitis, fatty liver and
hepatic cirrhosis. Specifically, improvement of nonalcoholic fatty
liver in the present invention indicates, for example, prevention
for fat deposition on the liver, or suppression of increase or
decrease in ALT (alanine aminotransferase), which is an item for
clinical examination of the liver function. The prevention of
nonalcoholic steatohepatitis in the present invention indicates
suppression of increase or decrease in ALT, which is an item for
clinical examination of the liver function.
[0024] In addition, among the nonalcoholic fatty liver diseases
described above, the present invention is particularly effective in
a case where fatty liver only is developed, in a case where
diabetes is not developed (complicated), in a case where liver
stiffness is low, or in a case where hepatic cirrhosis is not
developed. Particularly, the present invention is effective in the
case of treating, improving or preventing the nonalcoholic fatty
liver disease only. Even in a case where diabetes is developed, the
present invention is effective in a case where liver stiffness is
low, and in a case where diabetic treatment is not performed.
[0025] Development of nonalcoholic fatty liver only in the present
invention represents development of fatty liver only diagnosed as
nonalcoholic fatty liver in an ordinary diagnosis. Generally, the
development of nonalcoholic fatty liver only in the present
invention represents the state of a level that fat is deposited on
the liver with abdominal ultrasonography diagnosis, pictorial
diagnosis and the like, and abnormality is recognized in ALT, which
is an examination item of fatty liver, but a normal value or no
need of treatment is determined in other examination items.
[0026] The patient not developed with diabetes in the present
invention refers to a patient having a glycosylated hemoglobin
(HbA1c) concentration of 6.5% or less (NGSP value). In addition,
even though the glycosylated hemoglobin concentration is 6.5% or
more, the present invention is effective in a case where treatment
of diabetes is not performed.
[0027] The glycosylated hemoglobin is obtained by blood
examination, and thus refers to the ratio of HbA1c occupying the
total hemoglobin.
[0028] The present invention is also effective in the case of not
being complicated with high blood pressure or hyperlipidemia.
[0029] Herein, the high blood pressure refers to a patient who has
a systolic blood pressure (maximal high blood pressure) of 140 mmHg
or more and a diastolic blood pressure (minimal blood pressure) of
90 mmHg or more. The hyperlipidemia refers to a patient who has
high lipids, specifically cholesterol and neutral fat
(representative one is triglyceride) in the blood, and generally a
patient who has (1) hypercholesterolemia (total cholesterol value
in the blood: 220 mg/dL or more), (2) a disease of high LDL
cholesterol in the blood (low density lipoprotein (LDL) in the
blood: 140 mg/dL or more), (3) a disease of low HDL cholesterol in
the blood (HDL in the blood: less than 40 mg/dL), (4) a disease of
high triglyceride in the blood (high triglyceride in the blood: 150
mg/dL or more). A patient called the reserve for a disease of high
blood pressure or hyperlipidemia is also encompassed in the present
invention.
[0030] The disease having low liver stiffness in the present
invention refers to a disease corresponding to any one of the
followings. However, the disease having low liver stiffness is not
limited thereto, and the present invention is also effective for a
disease having low liver stiffness diagnosed by other methods.
[0031] (1) Measurement value of Type IV collagen (Type IV collagen
7S domain) in the serum is 4.5 ng/ml or less,
[0032] (2) Measurement value with FibroScan (manufactured by
Echo-Sense Inc.), of which the principle is transient elastography
that measures the propagation velocity of pulse oscillatory wave in
the tissue with elasticity (kPa) by an ultrasonic pictorial
analysis method as a noninvasive examination, is 9.0 kPa or
less.
[0033] The glutathione in the present invention refers to a reduced
glutathione or an oxidized glutathione or a mixture thereof. The
reduced glutathione represents a tripeptide having a structure of
.gamma.-L-Glu-L-Cys-Gly, and the oxidized glutathione represents
those obtained by binding of 2 molecules of the reduced glutathione
via S--S bond. The form of glutathione may be any one as long as it
contains glutathione as an active ingredient.
[0034] Glutathione of the present invention is not particularly
limited as long as it is obtained with a method that can be used as
a drug or food. Usually, glutathione of the present invention is
produced by synthesis using a microorganism such as yeast, or
oxygen, and the like.
[0035] A method for administering those containing glutathione as
an active ingredient is not particularly limited, and may include
oral administration and parental administration such as
intravenous, intraperitoneal or subcutaneous administration.
Specifically, the administration method may be any one of an oral
agent such as a tablet, a powder, a granule, a pill, a suspension,
an emulsion, an infusion or decoction, a capsule, a syrup, a
solution, an elixir, an extract, a tincture and a liquid extract,
or a parental agent such as an injection, a drop, a cream and a
suppository.
[0036] Yeast containing glutathione can be also orally
administered. As yeast containing a large amount of glutathione,
there is "Hithion Cobo MG" (manufactured by KOHJIN Life Sciences
Co., Ltd.), and as an yeast extract containing glutathione, there
is "Hithion extract YH" (manufactured by KOHJIN Life Sciences Co.,
Ltd.) or the like.
[0037] The dose of the present invention is not particularly
limited as long as it is an amount for expressing the functions
described above. The dose and the administration number of times in
the case of administration to human vary depending on the dosage
form, the age or the body weight of a subject and the like.
However, glutathione is administered usually 50 mg to 30 g,
preferably 100 mg to 10 g, and particularly preferably 200 mg to 3
g once to several times per day for an adult.
[0038] The composition of the present invention can be taken not
only as a drug, but also as functional food or nutritional
supplementary food, and in such a case, the composition of the
present invention may be taken in the intake amount of the previous
paragraph.
EXAMPLES
Example 1
(Evaluation of Efficacy for NASH/NAFLD)
[0039] To subjects (16 persons) whose meal or exercise therapy for
12 weeks or more was ineffective and who had NAFLD in 31 IU/L or
more of ALT, glutathione (manufactured by KOHJIN Life Sciences Co.,
Ltd.) was orally administered in 300 mg per one day. Liver biopsy
was performed before initiation of glutathione administration and
after 16 weeks of the administration, and blood examination was
performed every 4 weeks. The results are shown in Table 1.
[0040] The effects of the present invention are summarized in Table
2 with the subjects affected with the present invention (Case IDs 1
to 9) and the subjects not affected with the present invention
(Case IDs 10 to 16).
TABLE-US-00001 TABLE 1 Type IV collagen ALT (IU/L) 7s (ng/ml) HbA1C
(%) Case ID Age Sex 0 wk 4 wk 8 wk 12 wk 16 wk 0 wk 8 wk 16 wk 0 wk
4 wk 8 wk 12 wk 16 wk 1 39 M 67 77 39 43 48 4.3 3.9 4.3 5.2 5.3 5.1
5.4 5.3 2 71 F 96 35 34 23 50 4.9 4.9 4.9 3.8 6 5.9 6 6.1 3 39 F 61
48 37 32 43 3.1 2.9 3.4 6 6 6.1 6.1 6.2 4 41 M 96 24 19 20 25 4.7
4.4 3.9 5.4 5.2 5.3 5.3 5.3 5 45 M 63 46 31 38 42 3.4 3.6 3.6 3.8
3.7 3.8 3.8 3.8 6 41 M 76 62 65 59 94 3.4 3.4 3.4 3.4 5.5 5.7 5.9
5.8 7 31 M 193 133 138 125 135 4.4 4.3 4.9 5.3 5.3 5.2 5.3 5.3 8 55
M 59 34 33 34 44 4.5 4.5 4.6 5.8 5.7 5.8 5.9 5.9 9 45 F 97 87 81 60
93 3.7 3.7 3.7 5.4 5.3 5.4 5.4 5.4 10 64 M 97 90 77 72 86 5.3 4.8
4.9 6.9 6.8 6.7 6.9 7.4 11 60 M 69 31 53 54 63 4.4 4.9 4.4 6.9 7 7
7.4 7.4 12 61 F 66 60 52 59 64 6.5 6.7 6.9 8.9 9 8.9 8.5 8.3 13 46
M 91 96 73 76 86 7.7 7.4 7.4 7.1 6.9 7.1 7.4 7.5 14 74 F 47 53 65
48 63 4.8 4.6 4.4 6.2 6.4 6.6 6.5 6.4 15 64 F 33 30 37 32 27 4.4 4
3.3 7.8 7.6 7.6 7.8 7.6 16 66 F 48 45 41 40 40 5.6 None 4.8 7.1 7.2
7 6.9 7 FibroScan FibroScan (before treatment) (after treatment)
Case ID Age Sex CAP (dBe) E (kPa) CAP (dBe) E (kPa) 1 39 M 270 5.3
280 5.6 2 71 F 247 13.4 197 11.7 3 39 F 292 4.5 261 4.3 4 41 M 228
4.3 187 4.1 5 45 M 329 5.3 329 4.5 6 41 M 295 4.2 269 4.3 7 31 M
339 6.2 280 6.6 8 55 M 336 11.9 307 6.8 9 45 F 290 4.3 251 7.3 10
64 M 323 6.2 342 7.8 11 60 M 339 8.7 316 6.8 12 61 F Unmeasurable
Unmeasurable 13 46 M 362 17.5 372 16.8 14 74 F 314 8.4 307 7.4 15
64 F 303 10.5 271 6.5 16 66 F 286 11.5 348 17.5
[0041] Case IDs 1 to 9 in Table 1 is a group in which ALT before
initiation of the administration has improved by 20% or more after
the administration. Meanwhile, in consideration of variation of the
measurement, a case where there was a week at which ALT value after
initiation after administration of the present invention improved
by 20% or more in comparison to ALT value before the administration
(0 wk), was considered to be effective. Next, results of comparison
of various examination data before the administration of the
present invention in the group affected with the present invention
and the group not affected with the present invention are shown in
Table 2.
TABLE-US-00002 TABLE 2 Group not affected Group affected Before
administration of Before administration of Variable present
invention present invention p value Age (years) 57.7 .+-. 13.6 46.7
.+-. 11.9 <0.0559 NS Gender (male:female) 3:03 7:03 <0.4255
NS Internal medicine history (Absence:Presence) 0:06 5:05
<0.0142 # Madical history (Absence:Presence) 0:06 5:05
<0.0142 # Hypertension (Absence:Presence) 3:03 10:00 <0.0076
## Dyslipidemia (Absence:Presence) 0:06 5:05 <0.00142 ##
Diabeteus mellitus (Absence:Presence) 2:04 10:00 <0.0013 ## Body
weight (kg) 70.2 .+-. 15.0 75.9 .+-. 11.7 <0.7952 NS Body mass
index (kg/m2) 27.4 .+-. 4.4 27.3 .+-. 4.4 <0.4793 NS AST (IU/L)
53.5 .+-. 19.3 45.0 .+-. 19.3 <0.2044 NS ALT (IU/L) 57.8 .+-.
22.8 84.3 .+-. 39.6 <0.9200 NS GGT (IU/L) 63.2 .+-. 26.3 91.6
.+-. 67.0 <0.8292 NS Ferritin (ng/mL) 204.3 .+-. 209.9 224.0
.+-. 125.1 <0.5920 NS Low density lipoprotein cholesterol
(mg/dL) 113.3 .+-. 24.6 133.3 .+-. 23.2 <0.9372 NS High density
lipoprotein cholesterol (mg/dL) 53.3 .+-. 8.61 57.1 .+-. 14.9
<0.5841 NS Triglyceride (mg/dL) 211.3 .+-. 84.7 217.6 .+-. 195.5
<0.5288 NS Free fatty acid (.mu.Eq/L) 571.7 .+-. 267.8 704.0
.+-. 287.4 <0.8188 NS Fastin plasma glucose (mg/dL) 129.0 .+-.
57.6 102.8 .+-. 12.8 <0.0899 NS Immunoreactive Insulin
(.mu.U/mL) 15.5 .+-. 8.23 26.8 .+-. 27.1 <0.8280 NS HbA1C (%)
7.03 .+-. 1.25 5.50 .+-. 0.78 <0.0043 ## Platelet count (/mL)
23.0 .+-. 5.54 21.8 .+-. 3.38 <0.3097 NS Type IV collagen 7 s
5.40 .+-. 1.47 4.08 .+-. 0.63 <0.0120 # CAP 329.2 .+-. 35.5
300.5 .+-. 42.7 <0.0948 NS Elastography 11.3 .+-. 6.22 6.81 .+-.
3.38 <0.0412 # #, P < 0.05 ##, P < 0.01
Example 2
[0042] Effects of the present invention were further confirmed
using a mouse.
[0043] Mice (C57/B6J, 8 weeks old male) were divided into 4 groups
(5 animals each), and the first group (DB) was freely fed with
ordinary food (CertifiedDiet "MF" manufactured by Oriental Yeast
Co., ltd.). The second group (HFD) was freely fed with high-fat
food (High Fat Diet 32, manufactured by CLEA Japan, Inc.), was
freely given water only. The third group (HFD6) was freely fed with
high-fat food (High Fat Diet 32, manufactured by CLEA Japan, Inc.),
and glutathione was mixed with water so that glutathione can be
taken by 6 mg/kg/day. The fourth group (HFD60) was freely fed with
high-fat food (High Fat Diet 32, manufactured by CLEA Japan, Inc.),
and glutathione was mixed with water so that glutathione can be
taken by 60 mg/kg/day.
[0044] When the mouse was 20 weeks old, the body weight, the liver
weight, the serum aspartate aminotransferase (AST), the alanine
aminotransferase (ALT), the serum triglyceride (TG), the free fatty
acid value (FFA) and the total cholesterol value (T-cho) were
measured.
[0045] The results of the body weight and liver weight are shown in
FIGS. 1 and 2. Furthermore, the consumption amounts of feed and
water are shown in FIG. 3. There was no significant difference in
the consumption amounts of feed and water in all of the groups. In
the administration group of the present invention, decrease of the
body weight was recognized. Furthermore, as shown in FIG. 4, the
liver weight decreased dependently on the concentration of the
present invention, and decrease of the body weight ratio was also
recognized. It was found from this that deposition of fat on the
liver by high-fat food was suppressed.
[0046] FIG. 5 shows the results of the serum AST and the serum ALT,
and FIG. 6 shows TG (triglyceride value), FFA (free fatty acid
value) and T-cho (total cholesterol value). There were a
significant decrease in the HFD6 group and the HFD60 group in
comparison to the HFD group. In addition, when the HDF6 group and
the HFD60 group were compared, there was recognized a decrease
dependently on the concentration of the product of the present
invention.
[0047] Efficacy for nonalcoholic fatty liver by administration of
the product of the present invention was also confirmed in a mouse.
With the mouse model of Example 2, influence on the liver by
high-fat food intake only can be confirmed, and thus the effects of
the product of the present invention in Example 1 could be
observed.
[0048] From the results of the present Examples, the present
invention is particularly effective for improving the nonalcoholic
fatty liver disease in a case where the abnormality of a metabolic
disorder (high blood pressure, diabetes, lipid abnormality) is mild
or absent, in a case where medical history or internal medicine
history is absent, in a case where liver stiffness is low
(determined by the numerical value of elastography or Type IV
collagen), or in a case where diabetes is not complicated
(determined from the ratio of glycosylated hemoglobin).
BRIEF DESCRIPTION OF DRAWINGS
[0049] FIG. 1 is a graph showing progress of body weight.
[0050] FIG. 2 is a graph showing body weight at 20 weeks old.
[0051] FIG. 3 are graphs showing intake amounts of water and
feed.
[0052] FIG. 4 are graphs showing liver weight and ratio of liver
weight/body weight.
[0053] FIG. 5 are graphs showing serum AST and serum ALT.
[0054] FIG. 6 are graphs showing TG (triglyceride value), FFA (free
fatty acid value) and T-cho (total cholesterol value).
* * * * *