U.S. patent application number 16/769908 was filed with the patent office on 2020-12-10 for composition for enhancing immunity or preventing or treating neurodegenerative diseases by using goji berries, mulberries and jujubes.
The applicant listed for this patent is COSMAX NS, INC.. Invention is credited to Kwang Soo BAEK, Su Young CHOI, Hyunji KIM, Jin Hak KIM, Sang Woo KIM, Yoon Jong LEE, Young Min PARK, Jae Seok SHIM, Mann-Seok YOON.
Application Number | 20200384057 16/769908 |
Document ID | / |
Family ID | 1000005090966 |
Filed Date | 2020-12-10 |
United States Patent
Application |
20200384057 |
Kind Code |
A1 |
BAEK; Kwang Soo ; et
al. |
December 10, 2020 |
COMPOSITION FOR ENHANCING IMMUNITY OR PREVENTING OR TREATING
NEURODEGENERATIVE DISEASES BY USING GOJI BERRIES, MULBERRIES AND
JUJUBES
Abstract
The present invention relates to a composition for enhancing
immunity or a composition for preventing or ameliorating
neurodegenerative diseases, both of which contain, as an active
ingredient, a mixture extract of goji berries, mulberries and
jujubes or an extract mixture thereof.
Inventors: |
BAEK; Kwang Soo; (Seoul,
KR) ; KIM; Hyunji; (Gyeonggi-do, KR) ; CHOI;
Su Young; (Gyeonggi-do, KR) ; KIM; Jin Hak;
(Seoul, KR) ; SHIM; Jae Seok; (Gyeonggi-do,
KR) ; PARK; Young Min; (Gyeonggi-do, KR) ;
KIM; Sang Woo; (Gyeonggi-do, KR) ; YOON;
Mann-Seok; (Gyeonggi-do, KR) ; LEE; Yoon Jong;
(Seoul, KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
COSMAX NS, INC. |
Seoul |
|
KR |
|
|
Family ID: |
1000005090966 |
Appl. No.: |
16/769908 |
Filed: |
April 27, 2018 |
PCT Filed: |
April 27, 2018 |
PCT NO: |
PCT/KR2018/004917 |
371 Date: |
June 4, 2020 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 36/605 20130101;
A61K 2236/51 20130101; A61K 36/815 20130101; A61K 36/725 20130101;
A23L 33/105 20160801 |
International
Class: |
A61K 36/815 20060101
A61K036/815; A61K 36/605 20060101 A61K036/605; A61K 36/725 20060101
A61K036/725; A23L 33/105 20060101 A23L033/105 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 5, 2018 |
KR |
10-2018-0001904 |
Claims
1. A pharmaceutical composition for enhancing immunity comprising a
mixture extract of goji berries, mulberries and jujubes or an
extract mixture thereof as an active ingredient.
2. The pharmaceutical composition for enhancing immunity according
to claim 1, wherein the weight ratio of goji berry:mulberry:jujube
is 1 to 3:1 to 3:0.5 to 1.5.
3. The pharmaceutical composition for enhancing immunity according
to claim 1, wherein the mixture extract or the extract mixture is
lyophilized or spray dried.
4. The pharmaceutical composition for enhancing immunity according
to claim 1, wherein the mixture extract or the extract mixture
increases macrophage-derived TNF-.alpha. expression.
5. The pharmaceutical composition for enhancing immunity according
to claim 1, wherein the total concentration of the mixture extract
or the extract mixture is 1 .mu.g/ml to 10 mg/ml.
6. A health functional food for enhancing immunity comprising a
mixture extract of goji berries, mulberries and jujubes or an
extract mixture thereof as an active ingredient.
7. A pharmaceutical composition for preventing or treating
neurodegenerative diseases comprising a mixture extract of goji
berries, mulberries and jujubes or an extract mixture thereof as an
active ingredient.
8. The pharmaceutical composition for preventing or treating
neurodegenerative diseases according to claim 7, wherein the weight
ratio of goji berry:mulberry:jujube is 1 to 3:1 to 3:0.5 to
1.5.
9. The pharmaceutical composition for preventing or treating
neurodegenerative diseases according to claim 7, wherein the
mixture extract or the extract mixture is lyophilized or spray
dried.
10. The pharmaceutical composition for preventing or treating
neurodegenerative diseases according to claim 7, wherein the
mixture extract or the extract mixture increases the ratio of mBDNF
(mature BDNF) to hippocampal total BDNF.
11. The pharmaceutical composition for preventing or treating
neurodegenerative diseases according to claim 7, wherein the total
concentration of the mixture extract or the extract mixture is 1
.mu.g/ml to 10 mg/ml.
12. The pharmaceutical composition for preventing or treating
neurodegenerative diseases according to claim 7, wherein the
neurodegenerative disease is selected from the group consisting of
cerebral infarction, stroke, amnesia, memory impairment, dementia,
forgetfulness, Parkinson's disease, Alzheimer's disease, Pick's
disease, Creutzfeld-Kacob disease, Huntington's disease, and
amyotrophic lateral sclerosis.
13. A health functional food for preventing or ameliorating
neurodegenerative diseases comprising a mixture extract of goji
berries, mulberries and jujubes or an extract mixture thereof as an
active ingredient.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0001] The present invention relates to a composition for enhancing
immunity or preventing or ameliorating neurodegenerative diseases,
which comprises a mixture extract of goji berries, mulberries and
jujubes or an extract mixture thereof.
2. Description of the Related Art
[0002] Macrophage is a cell that regulates immune phenomena by
secreting various materials in the process of phagocytosis and
removal of bacteria or foreign substances and plays a pivotal role
in the immune response to antigens, and involves in antigen
presentation and non-specific immune response of lymphocytes, and
has direct injury activity against tumor cells. In addition, it is
known substances (LPS or natural products) responding to toll-like
receptors (TLR) activate macrophages to produce cytokines such as
IL-1, IL-6, IL-10, 1L-12 and TNF-.alpha. which can regulate
secondary immune responses such as defense against microbial
infection, activation of macrophages for phagocytosis, and
proliferation of T cells and B cells. IL-6 and TNF-.alpha. are
representative cytokines induced by macrophages and are known to
play a pivotal role in the inflammatory response following
bacterial infection and increase their amount in inflammatory
lesions. It has been reported that IL-6 is involved in the
differentiation of T cells and B cells by co-operation with IL-1
and has anticancer effects. TNF-.alpha. is known to have cytotoxic
and antiviral effects on certain cancer cells and play an important
role in various biological reactions occurring in acute and chronic
inflammatory diseases. IL-12, which is a cytokine that induces the
activation of NK cells and Th1-type immune response, is known to
serve to increase the reactivity to cellular foreign substances
such as cancer cells.
[0003] Meanwhile, as the life of human beings is extended,
neurodegenerative diseases such as cerebral infarction, stroke,
amnesia, memory impairment, dementia, forgetfulness, Parkinson's
disease, Alzheimer's disease, Pick's disease, Creutzfeld-Kacob
disease, Huntington's disease, and amyotrophic lateral sclerosis
are increasing. In neurodegenerative diseases, senile plaques
(A.beta.-plaques) called beta-amyloid (A.beta.) accumulate in the
brain tissues and neurofibrillary tangles (NFTs) appear in the
brain cells, resulting in degenerative atrophy throughout the brain
tissues and various associated symptoms.
[0004] Researches to show the immune enhancement efficacy through
these macrophages or to prevent, treat or ameliorate
neurodegenerative diseases are actively conducted, but there are no
studies on goji berries, mulberries and jujubes as a raw material
in relation to the symptoms.
SUMMARY OF THE INVENTION
[0005] The present invention is intended to provide a composition
for preventing, treating or ameliorating neurodegenerative diseases
while having an immune enhancement effect, which comprise a mixture
extract of goji berries, mulberries and jujubes or an extract
mixture thereof as an active ingredient.
[0006] However, the technical problem to be achieved by the present
invention is not limited to the above-mentioned problem, and
another problem not mentioned will be clearly understood by those
skilled in the art from the following description.
[0007] The present invention provides a pharmaceutical composition
for enhancing immunity comprising a mixture extract of goji
berries, mulberries and jujubes or an extract mixture thereof as an
active ingredient.
[0008] The weight ratio of goji berry:mulberry:jujube may be 1 to
3:1 to 3:0.5 to 1.5.
[0009] The mixture extract or the extract mixture may be
lyophilized or spray dried.
[0010] The mixture extract or the extract mixture may increase
macrophage-derived TNF-.alpha. expression.
[0011] The total concentration of the mixture extract or the
extract mixture may be 1 .mu.g/ml to 10 mg/ml.
[0012] In one embodiment of the present invention, there is
provided a health functional food for enhancing immunity comprising
a mixture extract of goji berries, mulberries and jujubes or an
extract mixture thereof as an active ingredient.
[0013] In other embodiment of the present invention, there is
provided a pharmaceutical composition for preventing or treating
neurodegenerative diseases comprising a mixture extract of goji
berries, mulberries and jujubes or an extract mixture thereof as an
active ingredient.
[0014] The weight ratio of goji berry:mulberry:jujube may be 1 to
3:1 to 3:0.5 to 1.5.
[0015] The mixture extract or the extract mixture may be
lyophilized or spray dried.
[0016] The mixture extract or the extract mixture may increase the
ratio of mBDNF (mature BDNF) to hippocampal total BDNF.
[0017] The total concentration of the mixture extract or the
extract mixture may be 1 .mu.g/ml to 10 mg/ml.
[0018] The neurodegenerative disease may be selected from the group
consisting of cerebral infarction, stroke, amnesia, memory
impairment, dementia, forgetfulness, Parkinson's disease,
Alzheimer's disease, Pick's disease, Creutzfeld-Kacob disease,
Huntington's disease, and amyotrophic lateral sclerosis.
[0019] In another embodiment of the present invention, there is
provided a health functional food for preventing or ameliorating
neurodegenerative diseases comprising a mixture extract of goji
berries, mulberries and jujubes or an extract mixture thereof as an
active ingredient.
Effect of the Invention
[0020] The composition according to the present invention, which
comprises a mixture extract of goji berries, mulberries and jujubes
or an extract mixture thereof as an active ingredient, has a
synergistic effect on the immune enhancement efficacy due to a
combination of goji berry, mulberry and jujube and thus it can be
usefully used as a pharmaceutical composition or a health
functional food without cytotoxicity. In particular, when the
weight ratio of goji berry, mulberry and jujube is 1 to 3:1 to
3:0.5 to 1.5, or when the mixture extract or the extract mixture is
lyophilized, it is possible to further improve the immune
enhancement efficacy.
[0021] In addition, the composition according to the present
invention has a synergistic effect on the prevention, treatment or
amelioration (especially improvement of memory) of
neurodegenerative diseases due to the combination of goji berry,
mulberry and jujube without cytotoxicity and thus it can be
usefully used as a pharmaceutical composition or a health
functional food. In particular, when the the weight ratio of goji
berry:mulberry:jujube is 1 to 3:1 to 3:0.5 to 1.5 or when the
mixture extract or the extract mixture is spray dried, it can
further improve the prevention, treatment or amelioration
(especially memory improvement) of neurodegenerative diseases.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 is a graph showing the results of evaluating the
cytotoxicity of the compositions prepared in Examples 1 and 2 and
Comparative Examples 1 to 3.
[0023] FIG. 2 is a graph comparing the measurement results of
macrophage-derived TNF-.alpha. expression of the compositions
prepared in Examples 1 and 2 and Comparative Examples 1 to 3.
[0024] FIG. 3 is a graph comparing the measurement results of the
ratio of mBDNF (mature BDNF) to hippocampal total BDNF of the
compositions prepared in Examples 1 and 2 and Comparative Examples
1 to 3.
DETAILED DESCRIPTION OF THE INVENTION
[0025] The present inventors have conducted research on plant
fruits in order to develop a composition for preventing, treating
or ameliorating neurodegenerative diseases while having immune
enhancement efficacy and found that a combination of goji berry,
mulberry and jujube has the synergetic effect on the said symptoms,
and thus completed the present invention.
[0026] Hereinafter, the present invention will be described in
detail.
[0027] Pharmaceutical Composition for Enhancing Immunity
[0028] The present invention provides a pharmaceutical composition
for enhancing immunity comprising a mixture extract of goji
berries, mulberries and jujubes or an extract mixture thereof as an
active ingredient.
[0029] As used herein, the term "goji berry" refers to a small red
fruit of Solanaceae, which is also called a Chinese matrimony vine.
A goji berry contains more than 500 times more vitamin C than
oranges and has more beta-carotene than carrots, which is excellent
for antioxidant activity, harmful oxygen suppression, and skin
health, and high iron content, which is essential for anemia and
thyroid gland. It has been known to improve digestion, protect
liver cells, relieve menopausal symptoms, and reduce joint and
muscle pain. A goji berry not only has anti-aging effect, but also
improves sleep disorders, and is effective in preventing
cardiovascular diseases. In addition, it promotes hormone
secretion, helps reduce body fat and manage weight.
[0030] As used herein, the term "mulberry" refers to a mulberry
fruit. It contains glucose, fructose, citric acid, malic acid,
tannin and pectin, as well as vitamins (A, B1, B2, D), calcium,
phosphorus and iron as a component. It is known as a tonic, and it
improves the function of the intestines, especially the liver and
kidneys. It relieves thirst, softens joints, degrades alcohol, and
relaxes the mind, making it effective for insomnia and
forgetfulness. In addition, it prevents whitening of hair, has a
hematopoietic effect, is used for treatment of rheumatism, and has
a reducing effect of blood sugar and cholesterol.
[0031] As used herein, the term "jujube" refers to a kind of plant
fruit which has a red brown surface, an elliptical shape and a
length of 1.5 to 2.5 cm, and has a sweet taste when it is red. The
fruit is used as a raw food as well as a dried fruit for
confectionery, cooking and medicinal purposes after drying
sufficiently. In addition, a jujube is processed to use as jujube
wine, jujube tea, jujube vinegar, jujube porridge. A honey jujube
as a processed product is popular in China, Japan, and Europe. In
oriental medicine, it is used as a diuretic, a tonic or a
palliative.
[0032] As used herein, the term "mixture extract" refers to a
material prepared by mixing raw materials and then extracting them
simultaneously. As used herein, the term "extract mixture" refers
to a material prepared by extracting raw materials individually and
then mixing the extracts.
[0033] As used herein, the term "immunity enhancement" is meant to
enhance or improve immune activity Immunity refers to a series of
in vivo responses to protect the body from antigens that are
foreign substances such as bacteria, viruses, cancer cells, and
blood and tissues of other human beings or animals.
[0034] The pharmaceutical composition for enhancing immunity
according to the present invention comprises a mixture extract of
goji berries, mulberries and jujubes or an extract mixture thereof
as an active ingredient, the mixture extract or extract mixture can
increase the macrophage-derived TNF-.alpha. expression without
cytotoxicity, which indicates that it has an immune enhancement
efficacy.
[0035] On the other hand, in the case of the single extract of goji
berries, the single extract of mulberries and the single extract of
jujubes, there is only a slight increase in the macrophage-derived
TNF-.alpha. expression compared to the control, which indicates
that there is little immune enhancement efficacy.
[0036] The mixture extract or the extract mixture uses goji
berries, mulberries and jujubes as a raw material, and the weight
ratio of goji berry:mulberry:jujube is preferably 1 to 3:1 to 3:0.5
to 1.5, the weight ratio of goji berry:mulberry:jujube is more
preferably 1.5 to 2.5:1.5 to 2.5:0.5 to 1.5, but is not limited
thereto. In this regard, when the weight ratio of goji
berry:mulberry:jujube is out of the above-described range, there is
a problem in that the degree of increase in the macrophage-derived
TNF-.alpha. expression is decreased compared to the control and
thus the immune enhancement efficacy is reduced.
[0037] First, the mixture extract is prepared by mixing goji
berries, mulberries and jujubes as a raw material and then
extracting them simultaneously. Preferably, water, C1 to C4 lower
alcohol or a mixture thereof is added to the mixture of goji
berries, mulberries and jujubes in an amount of 2 to 20 times
relative to the amount of the mixture of goji berries, mulberries
and jujubes, more preferably in an amount of 3 to 10 times, but is
not limited thereto. The extraction temperature is preferably
30.degree. C. to 100.degree. C., more preferably 70.degree. C. to
100.degree. C., but is not limited thereto. The extraction time is
preferably 1 hour to 20 hours, more preferably 3 hours to 10 hours,
but is not limited thereto. The extraction method may be any of
cold extraction, ultrasonic extraction and reflux cooling
extraction, but is not limited thereto. The number of extractions
is preferably 1 to 5 times, more preferably 2 to 3 times, but is
not limited thereto. Additionally, the mixture extract may be used
by diluting, concentrating or drying after diluting or
concentrating.
[0038] Next, the extract mixture is prepared by simultaneously
mixing the single extract of goji berries, the single extract of
mulberries and the single extract of jujubes. Preferably, water, C1
to C4 lower alcohol or a mixture thereof is added to the goji
berries, the mulberries or the jujubes in an amount of 2 to 20
times relative to the amount of the goji berries, the mulberries or
the jujubes, more preferably in an amount of 3 to 10 times, but is
not limited thereto. The extraction temperature is preferably
30.degree. C. to 100.degree. C., more preferably 70.degree. C. to
100.degree. C., but is not limited thereto. The extraction time is
preferably 1 hour to 20 hours, more preferably 3 hours to 10 hours,
but is not limited thereto. The extraction method may be any of
cold extraction, ultrasonic extraction and reflux cooling
extraction, but is not limited thereto. The number of extractions
is preferably 1 to 5 times, more preferably 2 to 3 times, but is
not limited thereto. Additionally, the extract mixture may be used
by diluting, concentrating or drying after diluting or
concentrating.
[0039] The mixture extract or the extract mixture may be
lyophilized or spray dried.
[0040] First, the lyophilization, referred to as freeze-drying, may
be carried out by freezing the mixture extract or the extract
mixture to be dried by rapidly lowering a temperature of a
container, and then adjusting a pressure inside the container close
to vacuum so that the solidified solvent contained in the mixture
extract or the extract mixture is immediately sublimed with water
vapor and dried. Specifically, the lyophilization may be performed
for 48 hours to 168 hours at a temperature of -30.degree. C. to
-50.degree. C.
[0041] Next, the spray drying may be carried out by spraying the
mixture extract or the extract mixture to be dried in hot air to
entrain fine water droplets of 1 mm or less in air stream.
Specifically, the spray drying can increase dry strength by
addition of dextrin.
[0042] When the mixture extract or the extract mixture is
lyophilized or spray dried, there is no significant difference in
the degree of cytotoxicity. However, when the mixture extract or
the extract mixture is lyophilized, the degree of increase of the
macrophage-derived TNF-.alpha. expression relative to the control
is greatly improved compared to spray drying, which indicates that
it has superior immune enhancement efficacy.
[0043] The total concentration of the mixture extract or extract
mixture is preferably 1 .mu.g/ml to 10 mg/ml, more preferably 1
.mu.g/ml to 1 mg/ml, but is not limited thereto.
[0044] That is, even if the mixture extract or extract mixture is
contained in the composition in a small concentration, it has the
advantage of exhibiting sufficient immune enhancement efficacy. In
this regard, if the total concentration of the mixture extract or
extract mixture is less than the above-described range, there is a
problem that it is difficult to exhibit sufficient immune
enhancement efficacy, and if the total concentration of the mixture
extract or extract mixture exceeds the above-described range, there
may be toxicity concerns, including cytotoxicity.
[0045] The pharmaceutical composition for enhancing immunity
according to the present invention may be formulated in the form of
oral preparations such as powders, granules, tablets, capsules,
suspensions, emulsions, syrups, aerosols, external preparations,
suppositories, and sterile solutions for injection according to
conventional methods, respectively. It may contain a suitable
carrier, an excipient or a diluent which is commonly used in the
manufacture of pharmaceutical compositions for formulation.
[0046] The carrier or excipient or diluent includes various
compounds or mixtures including lactose, dextrose, sucrose,
sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia
rubber, alginate, gelatin, calcium phosphate, calcium silicate,
cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl
pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate,
talc, magnesium stearate, mineral oil and the like.
[0047] When formulated, it may be used a diluent or an excipient
such as a filler, an extender, a binder, a wetting agent, a
disintegrating agent, and a surfactant which is commonly used.
[0048] Solid preparations for oral administration may be prepared
by mixing at least one excipient such as starch, calcium carbonate,
sucrose or lactose, gelatin and the like in the mixture extract or
extract mixture. In addition to simple excipients, lubricants such
as magnesium stearate and talc may also be used.
[0049] Liquid preparations for oral administration may include
suspensions, solvents, emulsions, and syrups, and may comprise
various excipients, such as a wetting agent, a sweetener, a
fragrance, and a preservative, in addition to commonly used simple
diluents such as water and liquid paraffin.
[0050] Preparations for parenteral administration may include
sterile aqueous solutions, non-aqueous solutions, suspensions,
emulsions, lyophilized preparations, suppositories, and the like.
As the non-aqueous solvent and suspending agent, propylene glycol,
polyethylene glycol, vegetable oil such as olive oil, injectable
ester such as ethyl oleate and the like can be used. As the base
for suppositories, witepsol, macrogol, tween 61, cacao butter,
laurin butter, glycerol gelatin and the like can be used.
[0051] Preferred dosages of the pharmaceutical composition for
enhancing immunity according to the present invention vary
depending on the condition of the patient, body weight, disease
severity, drug form, route of administration and administration
period, and may be appropriately selected by those skilled in the
art. However, for the desired effect, it may be administered at a
dose of 0.0001 to 2,000 mg/kg, preferably 0.001 to 2,000 mg/kg per
day. It may be administered once a day or several times a day in a
divided manner. However, the scope of the present invention is not
limited by the above dosage.
[0052] The pharmaceutical composition for enhancing immunity
according to the present invention can be administered to mammals
such as rats, mice, livestock and humans by various routes. All
modes of administration can be administered, for example, by oral,
by rectal or by intravenous, intramuscular, subcutaneous,
intrauterine or intracerebroventricular injection.
[0053] Health Functional Food for Enhancing Immunity
[0054] The present invention provides a health functional food for
enhancing immunity comprising a mixture extract of goji berries,
mulberries and jujubes or an extract mixture thereof as an active
ingredient.
[0055] Since the "goji berry", "mulberry", "jujube", "mixture
extract", "extract mixture" and "immunity enhancement" have been
described above, duplicate descriptions will be omitted.
[0056] For the health functional food for enhancing immunity
according to the present invention, when the mixture extract (or
extract mixture) is used as an additive for the health functional
food, it may be added as it is or used with other food or food
ingredients, and can be used appropriately according to the
conventional method. The amount of the active ingredient to be
mixed can be appropriately determined depending on the purpose of
use, such as prevention, health or treatment.
[0057] Formulations of health functional food may be in the form of
powders, granules, pills, tablets, capsules, as well as in the form
of general foods or beverages.
[0058] There is no particular restriction in the kind of the food.
Examples of the food include meat, sausage, bread, chocolate,
candy, snacks, confectionery, pizza, ramen, other noodles, gum, a
dairy product including ice cream, various soups, beverages, tea,
drinks, alcoholic beverages and vitamin complexes, etc. and may
include all foods in a conventional sense.
[0059] Generally, the mixture extract (or extract mixture) may be
added in an amount of 15 parts by weight or less, preferably 10
parts by weight or less, based on 100 parts by weight of the raw
material. However, in the case of long-term intake for the purpose
of health and hygiene or for health control, the amount may be less
than the above range. Also, in the present invention, since there
is no problem of safety in terms of using natural products, the
amount may be more than the above range.
[0060] The beverage of the health functional food according to the
present invention may contain various flavors or natural
carbohydrates and the like as an additional ingredient as in
general beverages. The above-described natural carbohydrates may be
monosaccharides such as glucose and fructose, disaccharides such as
maltose and sucrose, polysaccharides such as dextrin and
cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and
erythritol. As the sweetener, natural sweeteners such as thaumatin
and stevia extract, synthetic sweeteners such as saccharin and
aspartame, and the like can be used. The amount of the natural
carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to
0.03 g per 100 mL of the beverage according to the present
invention.
[0061] In addition, the health functional food for enhancing
immunity according to the present invention may contain various
nutrients, vitamins, electrolytes, flavoring agents, coloring
agents, pectic acid and salts thereof, alginic acid and salts
thereof, organic acids, protective colloid thickeners, pH
regulators, stabilizers, preservatives, glycerin, alcohols and
carbonating agents used in carbonated drinks. In addition, the
composition for enhancing immunity of the present invention may
contain fruit flesh for production of natural fruit juice, fruit
juice beverage and vegetable beverage. These ingredients can be
used alone or in combination. The ratio of such additives is not
limited, but it is generally selected from the range of 0.01 to 0.1
parts by weight relative to 100 parts by weight of the dietary
supplement of the present invention.
[0062] Therefore, the composition according to the present
invention comprises a mixture extract of goji berries, mulberries
and jujubes or an extract mixture thereof as an active ingredient
and has a synergistic effect on immune enhancement efficacy due to
the combination of goji berry, mulberry and jujube without
cytotoxicity and thus can be usefully used as a pharmaceutical
composition or a dietary supplement. In particular, when the weight
ratio of goji berry:mulberry:jujube is 1 to 3:1 to 3:0.5 to 1.5 or
when the mixture extract or the extract mixture is lyophilized, it
is possible to further improve the immune enhancement efficacy.
[0063] In addition, the composition according to the present
invention has a synergistic effect on preventing, treating or
ameliorating (especially, improving memory) neurodegenerative
diseases due to the combination of goji berry, mulberry and jujube
without cytotoxicity and thus can be usefully used as a
pharmaceutical composition or a health functional food. In
particular, when the weight ratio of goji berry:mulberry:jujube is
1 to 3:1 to 3:0.5 to 1.5 or when the mixture extract or the extract
mixture is spray dried, it is possible to further improve the
prevention, treatment or amelioration (especially, improvement of
memory) of neurodegenerative diseases.
[0064] Pharmaceutical Composition for Preventing and Treating
Neurodegenerative Diseases
[0065] The present invention provides a pharmaceutical composition
for preventing and treating neurodegenerative diseases comprising a
mixture extract of goji berries, mulberries and jujubes or an
extract mixture thereof as an active ingredient.
[0066] Since the "goji berry", "mulberry", "jujube", "mixture
extract" and "extract mixture" have been described above, duplicate
descriptions will be omitted.
[0067] As used herein, the term "neurodegenerative disease" refers
to at least one selected from the group consisting of cerebral
infarction, stroke, amnesia, memory impairment, dementia,
forgetfulness, Parkinson's disease, Alzheimer's disease, Pick's
disease, Creutzfeld-Kacob disease, Huntington's disease, and
amyotrophic lateral sclerosis.
[0068] The pharmaceutical composition for preventing or treating
neurodegenerative diseases according to the present invention
comprises a mixture extract of goji berries, mulberries and jujubes
or an extract mixture thereof as an active ingredient, wherein the
mixture extract or extract mixture can increase the ratio of mBDNF
(mature BDNF) to hippocampal total BDNF without cytotoxicity, which
indicates that it is possible to prevent, treat or ameliorate
neurodegenerative diseases.
[0069] On the other hand, in the case of the single extract of goji
berries, the single extract of mulberries and the single extract of
jujubes, there is only a slight increase in the ratio of mBDNF
(mature BDNF) to hippocampal total BDNF compared to the control,
which indicates that it is not possible to effectively prevent,
treat or ameliorate neurodegenerative diseases.
[0070] The mixture extract or the extract mixture uses goji berries
mulberries and jujubes as a raw material, and the weight ratio of
goji berry:mulberry:jujube is preferably 1 to 3:1 to 3:0.5 to 1.5,
the weight ratio of goji berry:mulberry:jujube is more preferably
1.5 to 2.5:1.5 to 2.5:0.5 to 1.5, but is not limited thereto. In
this regard, when the weight ratio of goji berry:mulberry:jujube is
out of the above-described range, there is a problem in that the
ratio of mBDNF (mature BDNF) to hippocampal total BDNF is decreased
compared to the control and thus it is not possible to effectively
prevent, treat or ameliorate neurodegenerative diseases.
[0071] First, the mixture extract is prepared by mixing goji
berries, mulberries and jujubes as a raw material and then
extracting them simultaneously. Preferably, water, C1 to C4 lower
alcohol or a mixture thereof is added to the mixture of goji
berries, mulberries and jujubes in an amount of 2 to 20 times
relative to the amount of the mixture of goji berries, mulberries
and jujubes, more preferably in an amount of 3 to 10 times, but is
not limited thereto. The extraction temperature is preferably
30.degree. C. to 100.degree. C., more preferably 70.degree. C. to
100.degree. C., but is not limited thereto. The extraction time is
preferably 1 hour to 20 hours, more preferably 3 hours to 10 hours,
but is not limited thereto. The extraction method may be any of
cold extraction, ultrasonic extraction and reflux cooling
extraction, but is not limited thereto. The number of extractions
is preferably 1 to 5 times, more preferably 2 to 3 times, but is
not limited thereto. Additionally, the mixture extract may be used
by diluting, concentrating or drying after diluting or
concentrating.
[0072] Next, the extract mixture is prepared by simultaneously
mixing the single extract of goji berries, the single extract of
mulberries and the single extract of jujubes. Preferably, water, C1
to C4 lower alcohol or a mixture thereof is added to the goji
berries, the mulberries or the jujubes in an amount of 2 to 20
times relative to the amount of the goji berries, the mulberries or
the jujubes, more preferably in an amount of 3 to 10 times, but is
not limited thereto. The extraction temperature is preferably
30.degree. C. to 100.degree. C., more preferably 70.degree. C. to
100.degree. C., but is not limited thereto. The extraction time is
preferably 1 hour to 20 hours, more preferably 3 hours to 10 hours,
but is not limited thereto. The extraction method may be any of
cold extraction, ultrasonic extraction and reflux cooling
extraction, but is not limited thereto. The number of extractions
is preferably 1 to 5 times, more preferably 2 to 3 times, but is
not limited thereto. Additionally, the extract mixture may be used
by diluting, concentrating or drying after diluting or
concentrating.
[0073] The mixture extract or the extract mixture may be
lyophilized or spray dried.
[0074] First, the lyophilization, referred to as freeze-drying, may
be carried out by freezing the mixture extract or the extract
mixture to be dried by rapidly lowering a temperature of a
container, and then adjusting a pressure inside the container close
to vacuum so that the solidified solvent contained in the mixture
extract or the extract mixture is immediately sublimed with water
vapor and dried. Specifically, the lyophilization may be performed
for 48 hours to 168 hours at a temperature of -30.degree. C. to
-50.degree. C.
[0075] Next, the spray drying may be carried out by spraying the
mixture extract or the extract mixture to be dried in hot air to
entrain fine water droplets of 1 mm or less in air stream.
Specifically, the spray drying can increase dry strength by
addition of dextrin.
[0076] When the mixture extract or the extract mixture is
lyophilized or spray dried, there is no significant difference in
the degree of cytotoxicity. However, when the mixture extract or
the extract mixture is spray dried, the ratio of mBDNF (mature
BDNF) to hippocampal total BDNF relative to the control is greatly
improved compared to lyophilizing, which indicates that it is
possible to effectively prevent, treat or ameliorate
neurodegenerative diseases.
[0077] The total concentration of the mixture extract or extract
mixture is preferably 1 .mu.g/ml to 10 mg/ml, more preferably 1
.mu.g/ml to 1 mg/ml, but is not limited thereto. That is, even if
the mixture extract or extract mixture is contained in the
composition in a small concentration, it has the advantage of
sufficiently preventing, treating or ameliorating neurodegenerative
diseases. In this regard, if the total concentration of the mixture
extract or extract mixture is less than the above-described range,
there is a problem that it does not sufficiently prevent, treat or
ameliorate neurodegenerative diseases, and if the total
concentration of the mixture extract or extract mixture exceeds the
above-described range, there may be toxicity concerns, including
cytotoxicity. Details regarding the formulation, effective amount,
and administration method of the pharmaceutical composition for
preventing or ameliorating neurodegenerative diseases according to
the present invention can be applied similarly as described in the
pharmaceutical composition for enhancing immunity.
[0078] Health Functional Food for Preventing or Ameliorating
Neurodegenerative Diseases
[0079] The present invention provides a health functional food for
preventing or ameliorating neurodegenerative diseases comprising a
mixture extract of goji berries, mulberries and jujubes or an
extract mixture thereof as an active ingredient.
[0080] Since the "goji berry", "mulberry", "jujube", "mixture
extract", "extract mixture" and "neurodegenerative disease" have
been described above, duplicate descriptions will be omitted.
[0081] Meanwhile, the amelioration of the neurodegenerative
diseases may mean the improvement of memory.
[0082] Details regarding the formulation, effective amount, and
administration method of the dietary supplement for preventing or
ameliorating neurodegenerative diseases according to the present
invention can be applied similarly as described in the health
functional food for enhancing immunity.
[0083] Therefore, the composition according to the present
invention comprises a mixture extract of goji berries, mulberries
and jujubes or an extract mixture thereof as an active ingredient
and has a synergistic effect on immune enhancement efficacy due to
the combination of goji berry, mulberry and jujube without
cytotoxicity and thus can be usefully used as a pharmaceutical
composition or a health functional food. In particular, when the
weight ratio of goji berry:mulberry:jujube is 1 to 3:1 to 3:0.5 to
1.5 or when the mixture extract or the extract mixture is
lyophilized, it is possible to further improve the immune
enhancement efficacy.
[0084] In addition, the composition according to the present
invention has a synergistic effect on preventing, treating or
ameliorating (especially, improving memory) neurodegenerative
diseases due to the combination of goji berry, mulberry and jujube
without cytotoxicity and thus can be usefully used as a
pharmaceutical composition or a health functional food. In
particular, when the weight ratio of goji berry:mulberry:jujube is
1 to 3:1 to 3:0.5 to 1.5 or when the mixture extract or the extract
mixture is spray dried, it is possible to further improve the
prevention, treatment or amelioration (especially, improvement of
memory) of neurodegenerative diseases.
[0085] Hereinafter, preferred examples are provided to help
understanding the present invention. However, the following
examples are merely provided to more easily understand the present
invention, and the contents of the present invention are not
limited by the following examples.
EXAMPLES
Example 1
[0086] About 40 g of goji berries (origin: China), about 40 g of
mulberries (origin: Pakistan), and about 20 g of jujubes (origin:
Korea) were mixed to prepare a mixture. The prepared mixture was
mixed with 10 (v/w) times water. The mixture was extracted under
reflux at 95.degree. C. for 4 hours, filtered under reduced
pressure, and concentrated in a rotary vacuum concentrator to
prepare a mixture extract. Then, it was lyophilized for 72 hours at
-40.degree. C.
Example 2
[0087] About 40 g of goji berries (origin: China), about 40 g of
mulberries (origin: Pakistan), and about 20 g of jujubes (origin:
Korea) were mixed to prepare a mixture. The prepared mixture was
mixed with 10 (v/w) times water. The mixture was extracted under
reflux at 95.degree. C. for 4 hours, filtered under reduced
pressure, and concentrated in a rotary vacuum concentrator to
prepare a mixture extract. Then, it was mixed with 50% by weight of
dextrin and spray dried.
Comparative Example 1
[0088] Goji berries (origin: China) were mixed with 10 (v/w) times
water, and the mixture was extracted under reflux for 4 hours at
95.degree. C. Thereafter, it was filtered under reduced pressure,
and concentrated in a rotary vacuum concentrator to prepare a
single extract. Then, it was mixed with 50% by weight of dextrin
and spray dried.
Comparative Example 2
[0089] Mulberries (origin: Pakistan) were mixed with 10 (v/w) times
water, and the mixture was extracted under reflux for 4 hours at
95.degree. C. Thereafter, it was filtered under reduced pressure,
and concentrated in a rotary vacuum concentrator to prepare a
single extract. Then, it was mixed with 50% by weight of dextrin
and spray dried.
Comparative Example 3
[0090] Jujubes (origin: Korea) were mixed with 10 (v/w) times
water, and the mixture was extracted under reflux for 4 hours at
95.degree. C. Thereafter, it was filtered under reduced pressure,
and concentrated in a rotary vacuum concentrator to prepare a
single extract. Then, it was mixed with 50% by weight of dextrin
and spray dried.
Experimental Example 1: Evaluation of Cytotoxicity
[0091] Cell viability was measured in order to evaluate the
cytotoxicity of the composition prepared in Examples 1 and 2 and
Comparative Examples 1 to 3.
[0092] First, mouse macrophage cell line RAW264.7 cells were
cultured at a density of 70-80% in a 100 mm cell culture dish using
RPMI 1640 medium containing penicillin (100 IU/ml) and streptomycin
(100 .mu.g/ml) and 10% FBS.
[0093] Then, it was analyzed using MTT
(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide)
assay. The cultured mouse macrophage cell line RAW264.7 cells were
adjusted to a concentration of 1.times.10.sup.6 cell/ml using RPMI
1640 medium, and then inoculated into a 96 well plate and
precultured at 5% CO.sub.2 and 37.degree. C. for 18 hours.
Thereafter, the medium was removed, and culture was performed in
the medium treated with the test material at a concentration shown
in the figures. After 24 hours, 10 .mu.l MTT solution (stock
concentration: 5 mg/ml) was added to induce an additional reaction
for 3 hours. 100 .mu.l DMSO was additionally added to each well to
terminate the reaction and dissolve formazan crystals. Cell
viability was measured by calculating the amount of MTT reduced to
formazan through the OD value obtained by measuring the absorbance
at 570 nm, and the results are shown in FIG. 1.
[0094] As shown in FIG. 1, the cell viability in the case of
treating with the compositions prepared in Examples 1 and 2 and
Comparative Examples 1 to 3 was found to be 80% or more, indicating
that there is no cytotoxicity.
Experimental Example 2: Determination of Macrophage-Derived
TNF-.alpha. Expression
[0095] In order to compare the immune enhancement efficacy of the
compositions prepared in Examples 1 and 2 and Comparative Examples
1 to 3, the TNF-.alpha. expression was measured.
[0096] First, the cultured mouse macrophage cell line RAW264.7
cells in Experimental Example 1 were adjusted to a concentration of
1.times.10.sup.6 cell/ml using RPMI 1640 medium, and then
inoculated into a 96 well plate and precultured at 5% CO.sub.2 and
37.degree. C. for 18 hours. Thereafter, the medium was removed, and
culture was performed in the medium treated with the test material
at a concentration shown in the figures. After 24 hours, the
supernatant was transferred to another 96 well plate by 100 .mu.l,
and measured the macrophage-derived TNF-.alpha. expression by using
an enzyme-linked immunosorbent assay (ELISA) kit of R&D systems
according to the manufacturer's instructions, and the results are
shown in FIG. 2.
[0097] As shown in FIG. 2, the macrophage-derived TNF-.alpha.
expression in the case of treating with the compositions prepared
in Examples 1 and 2 was found to be 100.00 pg/ml or more,
indicating that the immune enhancement efficacy is excellent. In
particular, the macrophage-derived TNF-.alpha. expression in the
case of treating with the composition (a weight ratio of goji
berry:mulberry:jujube=2:2:1) prepared in Examples 1 and 2 was found
to be 160.00 pg/ml or more, indicating that the immune enhancement
efficacy is significantly excellent.
[0098] In this regard, when comparing the immune enhancement
efficacy of the compositions prepared in Examples 1 and 2 to the
immune enhancement efficacy of the compositions prepared in
Comparative Examples 1 to 3 having the corresponding concentration
of goji berry, mulberry and jujube, the macrophage-derived
TNF-.alpha. expression in the case of treating with the
compositions prepared in Examples 1 and 2 was found to be improved
compared to the case of treating with the compositions prepared in
Comparative Examples 1 to 3, indicating that the combination of
goji berry, mulberry and jujube have a synergistic effect on the
immune enhancement efficacy.
Experimental Example 3: Measurement of Ratio of mBDNF to
Hippocampal Total BDNF
[0099] In order to compare the efficacy of preventing, treating or
ameliorating neurodegenerative diseases of the compositions
prepared in Examples 1 and 2 and Comparative Examples 1 to 3, total
BDNF expression and mature BDNF expression were measured.
[0100] First, the cultured mouse hippocampal cell line HT22 cells
in Experimental Example 1 were adjusted to a concentration of
1.times.10.sup.4 cell/ml using DMEM medium, and then inoculated
into a 96 well plate and preincubated at 5% CO.sub.2 and 37.degree.
C. for 18 hours. Thereafter, the medium was removed, and culture
was performed in the medium treated with the test material at a
concentration shown in the figures. After 24 hours, the supernatant
was transferred to another 96 well plate by 100 .mu.l, and measured
a concentration of total BDNF and a concentration of mature BDNF by
using an enzyme-linked immunosorbent assay (ELISA) kit of R&D
systems and calculated a ratio of mature BDNF to total BDNF, and
the results are shown in FIG. 3.
[0101] As shown in FIG. 3, the ratio of mBDNF to total BDNF in the
case of treating with the compositions prepared in Examples 1 and 2
was found to be 300% or more compared with the control, indicating
that the efficacy of preventing, treating or ameliorating
neurodegenerative diseases is excellent.
[0102] In this regard, when comparing the efficacy of preventing,
treating or ameliorating neurodegenerative diseases of the
compositions prepared in Examples 1 and 2 to the efficacy of
preventing, treating or ameliorating neurodegenerative diseases of
the compositions prepared in Comparative Examples 1 to 3 having the
corresponding concentration of goji berry, mulberry and jujube, the
ratio of mBDNF to hippocampal total BDNF in the case of treating
with the compositions prepared in Examples 1 and 2 is improved
compared to the case of treating with the compositions prepared in
Comparative Examples 1 to 3, indicating that the combination of
goji berry, mulberry and jujube have a synergistic effect on the
efficacy of preventing, treating or ameliorating neurodegenerative
diseases.
[0103] In the following, preparative examples of a composition
containing the mixture extract (or extract mixture) of the present
invention will be described. However, it is not intended to be
limited thereto, but is intended to be described in detail.
Preparative Example 1: Preparation of Powder
TABLE-US-00001 [0104] Mixture extract (or extract mixture) 20 mg
Lactose hydrate 100 mg Talc 10 mg
[0105] The above ingredients were mixed and then filled in an
airtight fabric to prepare a powder.
Preparative Example 2: Preparation of Tablet
TABLE-US-00002 [0106] Mixture extract (or extract mixture) 10 mg
Corn starch 100 mg Lactose hydrate 100 mg Stearate magnesium 2
mg
[0107] The above ingredients were mixed and then compressed
according to a conventional preparation method of tablets to
prepare a tablet.
Preparative Example 3: Preparation of Capsule
TABLE-US-00003 [0108] Mixture extract (or extract mixture) 10 mg
Microcrystalline cellulose 3 mg Lactose hydrate 14.8 mg Stearate
magnesium 0.2 mg
[0109] The above ingredients were mixed and then filled in a
gelatin capsule according to a conventional preparation method of
capsules to prepare a capsule.
Preparative Example 4: Preparation of Injection Formulation
TABLE-US-00004 [0110] Mixture extract (or extract mixture) 10 mg
Mannitol 180 mg Sterile distilled water for injection 2974 mg
Sodium monohydrogen phosphate 26 mg
[0111] The above ingredients were mixed and then filled in an
ampoule in the above-described content of ingredients per ampoule
(2 mL) according to a conventional preparation method of injections
to prepare an injection formulation.
Preparative Example 5: Preparation of Liquid Formulation
TABLE-US-00005 [0112] Mixture extract (or extract mixture) 10 mg
Isomerose 10 g Mannitol 5 g Purified water q.s. Lemon scent
q.s.
[0113] The above ingredients are dissolved in purified water
according to a conventional preparation method, and q.s. of lemon
scent is added thereto, and then purified water is adjusted to
total volume of 100 mL, sterilized and filled in a brown bottle to
prepare a liquid formulation.
Preparative Example 6: Preparation of Health Functional Food
TABLE-US-00006 [0114] Mixture extract (or extract mixture) 10 mg
Vitamin mixture q.s. Vitamin A acetate 70 .mu.g Vitamin E 1.0 mg
Vitamin B1 0.13 mg Vitamin B2 0.15 mg Vitamin B6 0.5 mg Vitamin B12
0.2 .mu.g Vitamin C 10 mg Biotin 10 .mu.g Nicotinamide 1.7 mg Folic
acid 50 .mu.g Calcium pantothenate 0.5 mg Mineral mixture q.s.
Ferrous sulfate 1.75 mg Zinc oxide 0.82 mg Magnesium carbonate 25.3
mg Potassium phosphate 15 mg Dicalcium phosphate 55 mg Potassium
citrate 90 mg Calcium carbonate 100 mg Magnesium chloride 24.8
mg
[0115] The above-mentioned composition ratio of vitamins and
minerals is presented in a preferred embodiment based on the
relatively suitable ingredients for dietary supplements, but the
mixing ratio may be arbitrarily modified. The above ingredients
were mixed and granulated according to a conventional preparation
method of dietary supplements to use for preparation of the dietary
supplement of the present invention.
Preparative Example 7: Preparation of Healthy Beverage
TABLE-US-00007 [0116] Scopoletin and rutin 10 mg Vitamin C 15 g
Vitamin E (powder) 100 g Ferrous lactate 19.75 g Zinc oxide 3.5 g
Nicotinamide 3.5 g Vitamin A 0.2 g Vitamin B1 0.25 g Vitamin B2 0.3
g Purified water q.s.
[0117] The above ingredients are mixed according to a conventional
preparation method of healthy beverages and heated with stirring at
85.degree. C. for about 1 hour. The resulting solution is collected
by filtration into a sterilized 2L container, sealed and
sterilized, and then stored in a refrigerator to use for
preparation of the healthy beverage composition of the present
invention.
[0118] The above composition ratio is presented in a preferred
embodiment based on the relatively suitable ingredients for
favorite beverages, but the mixing ratio may be arbitrarily
modified according to regional and ethnic preferences such as
demand class, demand country, and use purpose.
[0119] The above description of the present invention is intended
for illustration, and it will be understood by those skilled in the
art that it may be easily modified in other specific forms without
changing the technical spirit or essential features of the present
invention. Therefore, it should be understood the embodiments
described above are exemplary in all aspects and not
restrictive.
* * * * *