U.S. patent application number 16/778073 was filed with the patent office on 2021-08-05 for composition for anti-cancer, reducing anti-cancer side effects and suppressing cancer metastasis, including cannabis extract as active ingredient.
The applicant listed for this patent is FAMENITY CO., LTD.. Invention is credited to Ji Won LEE.
Application Number | 20210236570 16/778073 |
Document ID | / |
Family ID | 1000004927021 |
Filed Date | 2021-08-05 |
United States Patent
Application |
20210236570 |
Kind Code |
A1 |
LEE; Ji Won |
August 5, 2021 |
Composition for anti-cancer, reducing anti-cancer side effects and
suppressing cancer metastasis, including cannabis extract as active
ingredient
Abstract
The present invention relates to a composition for anti-cancer,
reducing anti-cancer side effects and suppressing cancer
metastasis, including a cannabis extract as an active ingredient,
and may provide a composition for anti-cancer, reducing anti-cancer
side effects and suppressing cancer metastasis, which decreases the
rate of cancer metastasis, does not have the occurrence of side
effects during internal use and administration, and does not cause
resistance by suppressing the activity of MMP-2 and MMP-9.
Inventors: |
LEE; Ji Won; (Gwacheon-si,
KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
FAMENITY CO., LTD. |
Uiwang-si |
|
KR |
|
|
Family ID: |
1000004927021 |
Appl. No.: |
16/778073 |
Filed: |
January 31, 2020 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 9/0014 20130101;
A61K 2236/333 20130101; A61K 36/185 20130101; A61K 9/0095 20130101;
A61P 35/00 20180101 |
International
Class: |
A61K 36/185 20060101
A61K036/185; A61K 9/00 20060101 A61K009/00; A61P 35/00 20060101
A61P035/00 |
Claims
1. A composition for anti-cancer, reducing anti-cancer side effects
and suppressing cancer metastasis, comprising a cannabis extract as
an active ingredient.
2. The composition of claim 1, wherein the cannabis extract
comprises cannabinoids and terpene.
3. The composition of claim 1, wherein the cancer is selected from
the group consisting of thyroid cancer, lung cancer, gastric
cancer, liver cancer, colorectal cancer, pancreatic cancer,
prostate cancer, uterine cancer, breast cancer, and skin
cancer.
4. The composition of claim 1, wherein the composition shows
effects of suppressing terminal cancer metastasis and reducing the
viability of cancer cells.
5. The composition of claim 1, wherein the cannabis extract
suppresses the activity of MMP-2 and MMP-9 to decrease the rate of
cancer metastasis.
6. The composition of claim 1, wherein the extract is extracted
using an extraction solvent selected from the group consisting of
water, C.sub.1 to C.sub.6 lower alcohols, and a mixture
thereof.
7. A functional food comprising the composition according to any
one of claims 1 to 5.
8. A skin external preparation comprising the composition according
to any one of claims 1 to 5.
9. A medicament comprising the composition according to any one of
claims 1 to 5.
Description
TECHNICAL FIELD
[0001] The present invention relates to a composition for
anti-cancer, reducing anti-cancer side effects and suppressing
cancer metastasis, including a cannabis extract as an active
ingredient. More particularly, the present invention relates to a
composition for anti-cancer, reducing anti-cancer side effects and
suppressing cancer metastasis, which decreases the rate of cancer
metastasis, is excellent in reducing the viability of cancer cells,
does not have side effects caused by internal use and
administration of the composition, and does not cause cancer to be
resistant, using a cannabis extract.
BACKGROUND ART
[0002] Cancer shows a high mortality rate worldwide, and is the
second most common cause of death next to cardiovascular diseases
in western societies. In particular, lung cancer is increasing due
to an increase in the smoking population and air pollution along
with the aging of the population, the intake of high-fat diets has
become common due to westernized eating habits, and colorectal
cancer, breast cancer, prostate cancer, and the like tend to
increase continuously due to a rapid increase in environmental
pollutants, an increase in alcohol consumption, and the like. Under
such circumstances, there is an urgent need for creating
anti-cancer substances capable of contributing to the promotion of
human health, the improvement in the quality of healthy life, and
the promotion of public health by enabling cancer to be prevented
and treated.
[0003] Malignant tumors spread from one organ, the primary site of
occurrence, to other tissues after the development in one organ
(the lungs, liver, kidneys, stomach, large intestine, rectum, and
the like) in most cases, and spread from the primary site of tumor
to other tissues is called metastasis.
[0004] Metastasis is a phenomenon accompanied by the progression of
a malignant tumor, and after malignant tumor cells proliferate and
acquire new genetic traits required for metastasizing as the cancer
progresses, the malignant tumor cells infiltrate the blood vessels
and lymph glands, circulate along the blood and lymph, settle and
then proliferate in other tissues. Recent studies have revealed
genetic traits associated with metastasis, and genetic testing of
the primary tissue may be used to infer a recurrence high-risk
group via metastasis to other organs in the future.
[0005] Treatment of metastasis of malignant tumors may be divided
into local treatment and systemic treatment, and the principle of
treatment of metastasis of malignant tumors differs depending on
the type of tumor and the tumor metastasis site. In the case of
some malignant tumors whose local symptoms become severe due to
metastasis, or a surgical treatment of metastasis is known to be
capable of modulating the natural course of malignant tumors, local
treatment strategies such as therapeutic surgery or radiation
therapy may be considered for metastasis. In general, when
metastasis occurs from a malignant tumor, it is helpful to treat
the tumor not only at the metastatic site but also at the primary
site together through systemic treatment such as anti-cancer
chemotherapy rather than local treatment. However, except for a
very small number of tumors, such as lymphoma, malignant tumors
where metastasis occurs are rarely cured completely.
[0006] The course of malignant tumors where metastasis occurs
varies, and is determined depending on the type of primary
malignant tumor and the overall tumor progression rate.
Complications may vary depending on which organ the malignant tumor
has metastasized to. For example, in the case of brain metastasis,
symptoms such as headache, visual field loss, and vomiting may
occur. In the case of bone metastasis, bone pain may occur, and
pathological fracture may occur. Mental fog may also occur due to
hypercalcemia accompanied by bone metastasis. Accordingly, early
detection of tumor through diagnosis and genetic testing of the
primary tumor are methods of preventing an increase in mortality
rate from metastasis.
[0007] Drugs developed for treating cancer to date are a systemic
injection or orally administered drug, and act non-specifically on
the whole body along the bloodstream and have low specificity for
cancer cells, and have a disadvantage in that many side effects
occur compared to surgery and radiation therapy because there are
many systemic side effects due to administration of the drug.
Meanwhile, no breakthrough drug has been developed, which can
prevent cancer cells from metastasizing to other organs without
showing cell toxicity.
[0008] Cancer pain is a pain caused by the cancer disease itself or
treatment, and is experienced by many patients who are currently
being treated and patients with advanced cancer.
[0009] Cancer pain depends on various factors including the type of
cancer, the stage of the disease, the site of the disease and the
patient's resistance to the pain, and cancer pain may be from the
primary cancer itself or from other sites of the body where the
cancer has spread (metastasized). As the tumor grows, the cancer
may exert pressure on nerves, bones, or other organs, which may
cause pain. Pain may also be caused by bone fracture,
disease-related infection or inflammation. Cancer pain may be
caused not only by the physical consequences of cancer at body
sites, but also by chemicals secreted from cancer cells and
tissues. The type of cancer pain may also be various. For example,
cancer pain may be acute, chronic, or breakthrough pain. Cancer
pain may also change during each pain period, and the severity and
frequency of pain may also vary.
[0010] Therefore, the control of pain in patients with cancer needs
to be performed in order for the patients to be able to carry out
their daily life.
[0011] The two main drug classes used to treat cancer pain are
opioid analgesics and non-steroidal anti-inflammatory drugs
(NSAIDs). These classes of drugs are typically administered
systemically. Systemic drug administration to reduce cancer pain is
often problematic. For example, systemic administration of opioids
for cancer pain may cause nausea, suppression of bowel function,
urine stagnation, suppression of lung functions, cardiovascular
effects and sedative action, and may cause undesired central
nervous system-mediated side effects, deterioration in respiratory
functions, sedative action, and drowsiness.
[0012] Therefore, there is a need for a composition free from side
effects even when the composition is systemically administered as
an effect capable of preventing the metastasis of cancer cells to
other organs.
PRIOR ART DOCUMENT
Patent Document
[0013] (Patent Document 1) KR 10-2015-0003111 A
SUMMARY OF THE INVENTION
[0014] The present invention has been made in an effort to provide
a composition for anti-cancer, reducing anti-cancer side effects
and suppressing cancer metastasis, including a cannabis extract as
an active ingredient.
[0015] The present invention has also been made in an effort to
provide a composition for anti-cancer, reducing anti-cancer side
effects and suppressing cancer metastasis, which shows effects of a
cannabis extract of suppressing terminal cancer metastasis and
reducing the viability of cancer cells.
[0016] The present invention has also been made in an effort to
provide a composition for anti-cancer, reducing anti-cancer side
effects and suppressing cancer metastasis, which is excellent in
effects of suppressing cancer metastasis and reducing the viability
of cancer cells, does not have side effects during the internal use
and administration of the composition, and does not cause cancer to
be resistant.
[0017] An exemplary embodiment of the present invention provides a
composition for anti-cancer, reducing anti-cancer side effects, and
suppressing cancer metastasis according to an exemplary embodiment
of the present invention includes a cannabis extract as an active
ingredient.
[0018] The cannabis extract includes cannabinoids and terpene.
[0019] The cancer includes those selected from the group consisting
of thyroid cancer, lung cancer, gastric cancer, liver cancer,
colorectal cancer, pancreatic cancer, prostate cancer, uterine
cancer, breast cancer, and skin cancer.
[0020] The composition shows effects of suppressing terminal cancer
metastasis and reducing the viability of cancer cells.
[0021] The cannabis extract includes those that suppress the
activity of MMP-2 and MMP-9 to decrease the rate of cancer
metastasis.
[0022] The extract includes those extracted using an extraction
solvent selected from the group consisting of water, C.sub.1 to
C.sub.6 lower alcohols, and a mixture thereof.
[0023] A functional food according to another exemplary embodiment
of the present invention is prepared using a composition for
anti-cancer, reducing anti-cancer side effects and suppressing
cancer metastasis, including a cannabis extract as an active
ingredient.
[0024] A skin external preparation according to still another
exemplary embodiment of the present invention is prepared using a
composition for anti-cancer, reducing anti-cancer side effects and
suppressing cancer metastasis, including a cannabis extract as an
active ingredient.
[0025] A medicament according to yet another exemplary embodiment
of the present invention is prepared using a composition for
anti-cancer, reducing anti-cancer side effects and suppressing
cancer metastasis, including a cannabis extract as an active
ingredient.
[0026] Hereinafter, the present invention will be described in more
detail.
[0027] As used herein, the term `extract` has a meaning commonly
used as a crude extract in the art as described above, but also
includes a fraction obtained by additionally fractionating an
extract in a broad sense. That is, an extract includes not only
those obtained using the above-described extraction solvent, but
also those obtained by additionally applying a purification
process. For example, a fraction obtained by allowing the extract
to pass through an ultrafiltration membrane having a predetermined
molecular weight cut-off value, and a fraction obtained through
various purification methods such as separation by means of various
chromatography methods (those manufactured for separation according
to the size, charge, and hydrophobicity or hydrophilicity)
additionally carried out are included in the extract of the present
invention.
[0028] To achieve the objects, a composition for anti-cancer,
reducing anti-cancer side effects, and suppressing cancer
metastasis according to an exemplary embodiment of the present
invention includes a cannabis extract as an active ingredient.
[0029] Cannabis is an annual plant of the Cannabaceae family, and
the subspecies thereof are classified into three subspecies such as
C. sativa subsp. sativa, C. sativa subsp. indica, and C. sativa
subsp. ruderalis. It is known that cannabis has been widely
cultivated for about 12,000 years, mainly in Central Asia, in
tropical and temperate regions, when legal regulations had not been
applied in the past, and cannabis was used for food in China around
6,000 BC. There is a record of using fiber obtained from cannabis
around 4,000 BC, and there is a document in the Chinese herbal book
that cannabis was first used for medical purposes in 2,727 BC.
However, in the twentieth century, cannabis has been strictly
regulated in cultivation and handling not only in Korea but also in
most countries due to side effects such as hallucinations. However,
the importance of cannabis for its excellent pharmacological action
has been increasingly recognized overseas, and there is an
increasing movement to permit the use of cannabis for therapeutic
purposes. In Korea, studies on cannabis are lacking due to strict
regulations on cannabis, and in particular, there have been almost
no studies on efficacy verification for medical cannabis and
problems on toxicity.
[0030] In the past, cannabis was used in various manners depending
on the site, and hemp or cannabis leaves as hemp leaves are said to
have an action of killing roundworms, and washing hair with water
boiled with cannabis leaves is said to causes hair to grow long and
shine. Further, cannabis has been used for asthma or prolonged
coughing, roundworm, analgesic action, anesthetic, and diuretic.
The root of cannabis refers to magen, and was believed to treat
difficult delivery and the absence of the placenta, relieve static
blood, and alleviate stone strangury, and it was said that as a
method of taking the root of cannabis, the root of cannabis was
decocted and the decocted water was taken. Mapi as the skin of
cannabis was said to treat bruise and heat strangury pain, and
mahua as the flower of cannabis was said to be used for treating
paralysis and itching. The flower spike of cannabis refers to
mafen, and has been utilized for difficult delivery, constipation,
gout, madness, insomnia, and the like.
[0031] The cannabis extract includes cannabinoids and terpene.
[0032] To date, about 400 compounds have been found in cannabis,
most of which are cannabinoids, terpenes, and phenolic compounds.
Among them, cannabinoids have been known as a representative active
ingredient of cannabis, but to date, about 90 kinds of cannabinoids
have been revealed, and many ingredients found only in cannabis are
also known. Cannabinol (CBN) was separated from cannabis in 1899,
but later it was known that cannabinol (CBN) was not a single
compound, and after cannabidiol (CBD) and tetrahydrocannabinol
(THC), which are pure compounds purified from cannabis, were
isolated in the 1930s, studies on ingredients of cannabis became
more active.
[0033] Efforts to develop drugs using specific ingredients of
cannabis have continued, and among them, THC and CBD, the main
compounds of medical cannabis have received the most attention for
therapeutic purposes. Studies have shown that CBD has no
psychotropic effects and is effective in reducing pain and
modulating epileptic seizures.
[0034] 100 or more terpene-based compounds that serve to produce
the aroma and taste of cannabis have been identified in cannabis,
and are present in the form of various monoterpenoids and
sesquiterpenoids. Although terpene has been shown to be associated
with various pharmacological effects such as anti-inflammatory
effects, studies on terpene compounds extracted from cannabis have
been insufficient compared to THC to date.
[0035] Terpene is known to exhibit a better effect when acting with
cannabinoids such as CBD and THC, and may improve absorption of
cannabinoids, overcome bacterial defense mechanisms and minimize
side effects.
[0036] The cancer includes those selected from the group consisting
of thyroid cancer, lung cancer, gastric cancer, liver cancer,
colorectal cancer, pancreatic cancer, prostate cancer, uterine
cancer, breast cancer, and skin cancer.
[0037] Thyroid cancer collectively refers to cancer that occurs in
the thyroid gland, and depending on the histological pattern,
progenitor cells of cancer and the degree of differentiation,
thyroid cancer is divided into papillary thyroid cancer, follicular
thyroid cancer, medullary thyroid cancer, undifferentiated thyroid
cancer, anaplastic cancer, metastatic thyroid cancer, and the like.
The thyroid gland is a butterfly-shaped organ located under the
thyroid cartilage and in front of the airway where air passes when
a person is breathing, and the thyroid gland functions to produce
and store thyroid hormones and deliver the hormones to the organs
that require the hormones.
[0038] Lung cancer refers to a malignant tumor that arises in the
lungs, and originates in the lungs themselves (primary lung
cancer), or also occurs when cancer originating from other organs
metastasizes to the lungs. The types of primary lung cancer are
classified into non-small cell lung cancer and small cell lung
cancer based on the size and morphology of the cancer cells, and
non-small cell lung cancer accounts for 80 to 85% of lung cancer,
which is again divided into glandular cancer (adenocarcinoma),
squamous cell carcinoma, large cell carcinoma, and the like. The
remaining small cell lung cancers generally have a high grade, and
at the time of discovery, most of the small cell lung cancers have
already metastasized to other organs, the contralateral lung, and
the mediastinum (space between both the lungs where the heart,
trachea, esophagus, aorta, and the like are located) through
lymphatic vessels or blood vessels.
[0039] Gastric cancer is a term that collectively refers to all
cancers that originate in the stomach, and gastric adenocarcinoma,
which accounts for the majority of gastric cancer, originates from
gastric mucosal gland cells (gland cells), and may be further
classified into various types depending on how the cells are
observed under a microscope. In addition, gastric cancer includes
all of the lymphoma originating in lymphoid tissue, interstitial
tumor originating in nerves and muscle tissues of the stomach,
sarcoma (malignant tumor derived from a non-epithelial tissue),
neuroendocrine cancer secreting hormones, and the like.
[0040] Liver cancer refers to the tumor primarily originating from
the liver, that is, the primary malignant tumor, and the general
public commonly also calls cancer that has metastasized from other
organs to the liver as liver cancer, but strictly speaking, liver
cancer refers only to primary cancer. Pathologically
(histologically), there are various types of primary liver cancer
such as hepatocellular carcinoma, bile duct epithelial carcinoma,
hepatoblastoma, and angiosarcoma, and among them, hepatocellular
carcinoma and bile duct epithelial carcinoma make up the majority
of primary liver cancer.
[0041] The large intestine is divided into the vermiform appendix,
the cecum, the colon, the rectum, and the proctodaeum, and colon is
again divided into the ascending colon, the transverse colon, the
descending colon, and the sigmoid colon, and among them, malignant
tumors that occur in the cecum, colon and rectum are called
colorectal cancer. Most colorectal cancers refers to glandular
cancer (adenocarcinoma), that is, cancer occurring in glandular
cells of the mucous membranes, and other primary types such as
lymphoma, malignant carcinoid, and leiomyosarcoma may occur.
[0042] Pancreatic cancer is a mass (lump) composed of cancer cells
occurring in in the pancreas, and 90% or more of pancreatic cancer
is glandular cancer in which cancer occurs in glandular cells of
the pancreatic duct. There are many types of pancreatic tumors, the
most common of which are benign cystic tumors (cystoma), and
mesenchymal tumors such as serous and mucinous cystic tumors,
intraductal papillary mucinous tumor, solid pseudopapillary tumor,
lymphoepithelial cyst, and cystic teratoma belong to the benign
cystic tumors. Malignant tumors include neuroendocrine tumors in
addition to pancreatic ductal adenocarcinoma and acinar cell
carcinoma, which are exocrine tumors. Some cysts are malignant, and
those that were initially benign may become malignant.
[0043] Prostate cancer is a cancer that originates in the prostate
and is mostly adenocarcinoma that originates in prostate cells.
Prostate cancer cells continue to proliferate out of normal
control, invade other nearby tissues, or metastasize to distant
tissues through blood vessels and lymphatic vessels. The types are
classified according to the degree of differentiation of tumor
tissues and the characteristics of cells. The benign tumor that
originates in the prostate is prostatic hyperplasia, and the
malignant tumor is called prostate cancer.
[0044] Uterine cancer collectively refers to malignant tumor that
originates in the uterus, and is divided into cervical cancer and
endometrial cancer according to the site of occurrence Cervical
cancer and endometrial cancer are carcinomas that completely differ
not only in anatomical development site but also in disease causes,
symptoms and syndromes, progress aspect, histological
characteristics, treatment methods, and the like. Cervical cancer
is more common in Korean women, endometrial cancer is more common
in Western women, but the incidence rate of endometrial cancer in
Korean women is increasing.
[0045] Breast cancer is a type of malignant tumor that can spread
outside the breasts and be life-threatening, and is divided into
cancers that occur in parenchymal tissues such as lactiferous duct
and the lobule and cancers that occur in other stromal tissues,
depending on the site of occurrence. Lactiferous ductal and lobular
cancers are again divided into invasive and non-invasive breast
cancers, depending on the extent to which the cancer cells have
spread to surrounding tissues. Male breast cancers account for 1%
or less of female breast cancers, and invasive ductal carcinoma is
most commonly found.
[0046] Skin cancer is a cancer that originates in the skin which is
the outermost layer of the human body, and skin cancer that
originates in the skin from the onset is called primary skin
cancer, and skin cancer that originates in other organs and has
metastasized to the skin is called metastatic skin cancer. In
general, skin cancer refers to only primary skin cancer that
originates in the skin from the outset, and refers to only the
three most commonly occurring squamous cell carcinoma, basal cell
carcinoma, and malignant melanoma in a strict sense. Skin cancers
may be broadly divided into malignant melanoma and non-melanoma
skin cancer.
[0047] The present invention is those that suppress the activity of
MMP-2 and MMP-9 to decrease the rate of cancer metastasis and can
be used for those that may show an anti-cancer effect, and is not
limited to the examples.
[0048] The composition shows effects of suppressing terminal cancer
metastasis and reducing the viability of cancer cells.
[0049] Cancer may be divided into early, advanced, and terminal
stages at diagnosis, and the early stage refers to a period when
cancer can be completely cured by appropriate treatment and the
advanced stage refers to a period when cancer cannot be completely
cured, but prolonging life can be expected through aggressive
anti-cancer treatment (surgery, radiation therapy, anti-cancer
chemotherapy (anti-cancer drug treatment)). In contrast, the
terminal stage is a period when such aggressive anti-cancer
treatment cannot contribute to the prolonging of life, but rather
increases only the risk of side effects, and even chemotherapy,
which plays an important role in the treatment of terminal cancer,
has been a major obstacle to treatment due to the resistance of
cancer to anti-cancer drugs, which occurs during chemotherapy.
[0050] In particular, the terminal stage is a step in which cancer
has grown beyond a certain size, and is a period when the
progression to cancer is promoted by contributing to the growth and
metastasis of cancer, evasion of immune mechanism, and the like,
and a patient suffers from various symptoms including pain from
advanced disease, and pain regulation, dyspnea regulation, and the
like using various analgesics are performed.
[0051] Thus, in the present invention, as the composition of the
present invention is used as a composition for anti-cancer,
reducing anti-cancer side effects and suppressing cancer metastasis
using a cannabis extract, it is possible to provide a composition
as an anti-cancer agent which lowers the occurrence of side effects
caused by internal use and administration and does not cause
resistance, unlike a chemotherapeutic agent.
[0052] More specifically, it is possible to provide a composition
which is excellent in effects of treating terminal cancer by
including a cannabis extract as an active ingredient to suppress
the metastasis of terminal cancer and reduce the viability of
cancer cells.
Preferably, the composition for anti-cancer, reducing anti-cancer
side effects and suppressing cancer metastasis may further include
an Erigeron annuus (L.) Pers extract, a Ceratonia siliqua (L.)
Taub. extract, and a Stellaria media extract.
[0053] The Erigeron annuus (L.) Pers is a native of North America,
a biennial grass growing in fields, plains and roadsides in various
parts of Korea, and a genus Chrysanthemum plant, and various
physiological activities thereof such as dyspepsia, malaria,
enteritis, hepatitis, diuretic action or hypoglycemic action are
known.
[0054] The Ceratonia siliqua (L.) Taub. is s an evergreen
broad-leaved shrub that grows about 10 m in height, and is well
tolerated by drought. The leaves contain resin. In the fall, small
faint green-brown flowers bloom and long green pods run. The pods,
when ripe, turn chocolate-colored and contain small, glossy, hard
beans therein. Carob gum, which softens the skin, is popular as a
skin pack and is also used to treat diarrhea.
[0055] The Stellaria media is a biennial herb of the family
Caryophyllaceae, grows mainly on a roadside or in an embankment
around the end of a field, is about 10 to 20 cm tall, and is rich
in minerals such as protein, calcium and iron. The Stellaria media
strengthens the stomach and intestines, cleanses the blood and
improves milk production. The Stellaria media may also treat
inflammation such as gum disease, tooth decay, appendicitis,
enteritis, and bowel ulcers.
[0056] However, no studies on the suppression of cancer metastasis
using these plants have been reported.
[0057] When the natural extracts are used in combination, the
effect of suppressing cancer metastasis is enhanced due to the
mixing action among the constituent ingredients.
[0058] As the Erigeron annuus (L.) Pers extract, the Ceratonia
siliqua (L.) Taub. extract and the Stellaria media extract are
additionally included, it is possible to provide a composition
having excellent preference by neutralizing the taste and aroma
peculiar to the cannabis extract.
[0059] Preferably, the composition of the present invention may
include 20 to 40 parts by weight of the Erigeron annuus (L.) Pers
extract, 20 to 40 parts by weight of the Ceratonia siliqua (L.)
Taub. extract, and 20 to 40 parts by weight of the Stellaria media
extract based on 100 parts by weight of the cannabis extract. When
the composition of the present invention is used as a complex
extract within the above-range, it is possible to exhibit excellent
cancer metastasis suppression and anti-cancer effects and
simultaneously provide the composition as a composition having
excellent preference.
[0060] The cannabis extract includes those that suppress the
activity of MMP-2 and MMP-9 to decrease the rate of cancer
metastasis.
[0061] Matrix metalloproteinase (MMP) is an extracellular matrix
degrading enzyme, acts as a regeneration, embryo development, and
neovascularization factor in vivo or is used as a protein to
suppress the tumor cell apoptosis or activate the growth factors,
and is a key enzyme involved in extracellular matrix degradation
and cell migration.
[0062] Among such MMPs, particularly, MMP-2 and MMP-9 are known to
act specifically to type IV collagen and play an important role in
cancer invasion and metastasis.
[0063] Cancer metastasis and invasion are fundamental
characteristics of malignant cancer cells. Cancer invades the blood
vessels as well as metastases in the early stage. Cancer cells go
through several important steps in the processes of invasion and
metastasis. In these processes, the degradation of the
extracellular matrix that makes up the basement membrane is an
essential early step, because the extracellular matrix surrounding
the cancer tissue and the basement membrane are regarded as walls
in the invasion of cancer. Various proteolytic enzymes participate
in this process and reach the final step through degradation of the
extracellular matrix and basement membrane, which are external
environmental barriers. However, a proteolytic enzyme secreted from
cells is an inactive form of pro-MMP-9, which is activated through
a series of enzyme activations, including the production of an
active form of plasminogen (plasmin) by a urokinase-type
plasminogen activator (uPA). Activated MMP-9 enhances the ability
to invade cancer cells.
[0064] Thus, the present invention may provide a composition for
anti-cancer, reducing anti-cancer side effects and suppressing
cancer metastasis, which delays the rate of invasion and metastasis
of cancer cells through effects of suppressing the enzymatic
activity of MMP-2 and MMP-9 enzymes of a cannabis extract.
[0065] The extract includes those extracted using an extraction
solvent selected from the group consisting of water, C.sub.1 to
C.sub.6 lower alcohols, and a mixture thereof.
[0066] Specifically, in order to prepare a cannabis extract, a
natural extract may be obtained by including: grinding a natural
product; leaching the ground product by using an organic solvent;
leaching a sample, and then drying the sample; re-leaching the
dried sample by using an organic solvent; leaching the sample, and
then drying the sample; leaching the sample by using water; and
leaching the resulting product.
[0067] The method of obtaining the natural extract may further
include performing fractionation on the natural extract extracted
by using the organic solvent by using an organic solvent.
[0068] The extraction solvent may be used 2 to 50 times, more
specifically 2 to 20 times, based on the weight of the sample. For
extraction, the sample may be left to stand in the extraction
solvent for leaching for 1 to 72 hour, more specifically, 24 to 48
hours.
[0069] The extract may be prepared in a powder state by additional
processes such as distillation under reduced pressure and freeze
drying or spray drying, and the method include obtaining an extract
by an extraction method selected from the group consisting of a
solvent extraction method, an ultrasonic extraction method, a
reflux extraction method, a leaching method, a fermentation method
and a processing method.
[0070] The ultrasonic extraction method performs the reaction at 30
to 50.degree. C. for 0.5 to 2.5 hours, and the extraction solvent
is obtained from water or a 50 to 100% alcohol having 1 to 6 carbon
atoms. Specifically, the extract is extracted at 40 to 50.degree.
C. for 1 to 2.5 hours, and an extraction solvent is obtained from
water or a 70 to 80% alcohol having 1 to 6 carbon atoms.
[0071] The reflux extraction method is performed by 10 to 30 g of a
ground material of the natural product based on water and 100 mL of
an alcohol having 1 to 6 carbon atoms, a reflux time of 1 to 3
hours, and a 50 to 100% alcohol having 1 to 6 carbon atoms or
water. More specifically, the method is performed by 10 to 20 g of
a ground material of the natural product based on 100 mL of an
alcohol having 1 to 6 carbon atoms or 100 mL of water, 10 to 20 g
of a ground material of a natural product, a reflux time of 1 to 2
hours, and a 70 to 90% alcohol having 1 to 4 carbon atoms, or
water.
[0072] The leaching method is performed at 15 to 30.degree. C. for
24 to 72 hours, and as an extraction solvent, water or a 50 to 100%
alcohol having 1 to 6 carbon atoms is used. More specifically, the
leaching method is performed at 20 to 25.degree. C. for 30 to 54
hours, and the extraction solvent is obtained by water or a 70 to
80% alcohol having 1 to 6 carbon atoms.
[0073] After extraction, the extract may be fractionated by
sequentially applying new fractionation solvents. For a
fractionation solvent used during the fractionation, the solvent is
one or more selected from the group consisting of water, hexane,
butanol, ethyl acetic acid, ethyl acetate, methylene chloride, and
a mixture thereof, preferably, ethyl acetate or methylene
chloride.
[0074] A functional food according to another exemplary embodiment
of the present invention is prepared using a composition for
anti-cancer, reducing anti-cancer side effects and suppressing
cancer metastasis, including a cannabis extract as an active
ingredient.
[0075] "Functional food" as defined herein means a food
manufactured and processed using raw materials or ingredients that
have functional properties that are useful for the human body
according to Act No. 6727 on functional foods, and "functional" is
meant to be taken for the purpose of regulating nutrients to the
structure and function of the human body, or obtaining effects
useful for public health use, such as physiological effects.
[0076] A skin external preparation according to still another
exemplary embodiment of the present invention is prepared using a
composition for anti-cancer, reducing anti-cancer side effects and
suppressing cancer metastasis, including a cannabis extract as an
active ingredient.
[0077] A medicament according to yet another exemplary embodiment
of the present invention is prepared using a composition for
anti-cancer, reducing anti-cancer side effects and suppressing
cancer metastasis, including a cannabis extract as an active
ingredient.
[0078] A dosage form of the medicament of the present invention may
be in a preferred form according to the use method, and in
particular, the medicament of the present invention may be
formulated using a method publicly known in the art so as to
provide a rapid, sustained, or delayed release of an active
ingredient after being administered to mammals. Specific examples
of the dosage form include granules, powders, syrups, solutions,
suspensions, pills, infuses, tablets, suppositories, injections,
spirits, capsules, pills, soft or hard gelatin capsules, and the
like.
[0079] The preferred dose for the medicament of the present
invention depends on the condition and body weight, the degree of
the disease, the form of drug, the administration route and the
duration, but may be appropriately selected by a person having
ordinary skill in the art to which the present invention
pertains.
[0080] According to the composition for anti-cancer, reducing
anti-cancer side effects and suppressing cancer metastasis,
including the cannabis extract of the present invention as an
active ingredient, it is possible to provide a composition for
anti-cancer, reducing anti-cancer side effects and suppressing
cancer metastasis, which is excellent in an effect of suppressing
cancer metastasis, exhibits an effect of reducing the viability of
cancer cells, does not have the occurrence of side effects during
internal use and administration, and does not cause resistance by
suppressing the activity of MMP-2 and MMP-9 enzymes.
BRIEF DESCRIPTION OF THE DRAWINGS
[0081] FIG. 1 is an experimental result for the viability of cancer
cells of a composition according to an exemplary embodiment of the
present invention.
[0082] FIG. 2 is an experimental result for the resistance of a
cancer cell line SNU38M.RTM. to the composition according to an
exemplary embodiment of the present invention.
[0083] FIG. 3 is an experimental result for the resistance of a
cancer cell line AGS.RTM. to the composition according to an
exemplary embodiment of the present invention.
[0084] FIG. 4 is an experimental result showing the activity of
MMP-2 and MMP-9 enzymes of the composition according to an
exemplary embodiment of the present invention.
DETAILED DESCRIPTION
[0085] Hereinafter, the Examples of the present invention will be
described in detail such that a person skilled in the art to which
the present invention pertains can easily carry out the present
invention. However, the present invention can be implemented in
various different forms, and is not limited to the Examples
described herein.
Preparation Example: Preparation of Extract
[0086] Preparation of Cannabis Extract
[0087] Cannabis including leaves and flowers was washed thoroughly
with running water and then air-dried completely. The dried
cannabis was pulverized with a mixer and then prepared as a powder.
After 50% ethanol as an extraction solvent was added to the powder
sample at a ratio of 1:10 (w:v) and then the powder sample was
completely immersed, extraction was performed repeatedly three
times at 80.degree. C. under reflux for each 3 hours. The liquid
extract was filtered with a Whatman No. 2 filter paper. A cannabis
extract (CE) was prepared by concentrating the filtrate at
60.degree. C. under reduced pressure.
[0088] 2. Preparation of Other Natural Extracts
[0089] An Erigeron annuus (L.) Pers extract (EE), a Ceratonia
siliqua (L.) Taub. extract (IE), and a Stellaria media extract (SE)
were prepared using a method which is the same as the preparation
method of the cannabis extract (CE).
[0090] 3. Preparation of Complex Extract
[0091] A complex extract was formed by mixing the cannabis extract
(CE), the Erigeron annuus (L.) Pers extract (EE), the Ceratonia
siliqua (L.) Taub. extract (IE), and the Stellaria media extract
(SE) as shown in the following Table 1.
TABLE-US-00001 TABLE 1 MX1 MX2 MX3 MX4 MX5 MX6 CE 100 100 100 100
100 100 EE -- 10 20 30 40 50 IE -- 10 20 30 40 50 SE -- 10 50 30 40
50 (Unit: parts by weight)
Experimental Example 1: Cytotoxicity Experiments
[0092] Toxicity Experiments
[0093] In order to test the toxicity of cannabis extract (CE) and
complex extracts (MX2 to MX6), differences in toxicity and side
effects during the administration of the complex extracts were
confirmed in a rat repetitive dose toxicity experiment.
[0094] Six-week-old SD male and female rats were divided into 10
per group (5 males and 5 females), and the complex extracts MX1 to
MX6 were administered to the groups, and after each drug was
dissolved in a 0.5% MC solution, oral administration once daily at
the same morning time was repeated for 13 weeks.
[0095] As a single dose, the solution was administered in an amount
of 3.75 mg/kg to 5 mg/kg. Thereafter, the mortality rate, general
symptoms, weight change, and food and water intake were
observed.
[0096] As a result, no dead individuals occurred during the
experimental period. In view of the experimental results, it was
confirmed that the cannabis extract (CE), the Erigeron annuus (L.)
Pers extract (EE), the Ceratonia siliqua (L.) Taub. extract (IE),
the Stellaria media extract (SE), and a mixture thereof had no
toxicity problems.
[0097] Cancer Cell Viability Experiment
[0098] 2-1. Cannabis Extract (CE)
[0099] The cell viability of HCT116 cells and HT-29 cells as human
colorectal cancer cells to which the cannabis extract (CE) was
administered was measured.
[0100] First, HCT116 cells and HT-29 cells were cultured in a
humidified incubator under conditions of an RPMI 1640 (Sigma
Chemical CO.) medium including 10% fetal bovine serum (GIBCO), a
temperature of 37.degree. C., and 5% CO2/95% air. In this case, the
culture medium was replaced once every other day. After confluent
growth, the cells were subcultured by trypsin treatment with a
0.25% trypsin-EDTA solution. After the cells were cultured for 4 to
5 days, the cells were aliquoted at a density of 5.times.10.sup.4
cells/well in a 24-well plate, and the medium volume of each well
was adjusted to 1 ml.
[0101] Thereafter, after the cells were treated with the cannabis
extract (CE) prepared in the Preparation Example at concentrations
of 0 .mu.m, 10 .mu.m, 20 .mu.m, 30 .mu.m, 40 .mu.m, 50 .mu.m, and
100 .mu.m, respectively and cultured for 24 hours, 100 .mu.l of
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
(MTT); 5 g MTT/l in H2O] was added thereto, and then the cells were
further cultured for 4 hours, and 200 .mu.l of dimethyl sulfoxide
(DMSO) was added to the wells containing each cell and mixed with a
pipette in order to dissolve the reduced MTT crystals. The relative
cell viability was determined by scanning with a microplate reader
(Molecular Devices, Menlo Park, Calif.) with a 540 nm filter.
[0102] The results thereof are illustrated in FIG. 1, and it was
confirmed that the viability of HCT116 cells and HT-29 cells, which
are human colorectal cancer cells to which cannabis extract (CE)
was administered, was decreased.
[0103] In view of the experimental results, it was confirmed that
the cannabis extract (CE) was effective for reducing the survival
of cancer cells.
[0104] 2-2. Composite Extract
[0105] In order to examine the cancer cell viability of the complex
extracts (MX2 to MX6), the same experiment as the cell viability
experiment of the cannabis extract (CE) was performed, and the
results thereof are shown in comparison with the relative effect on
the cannabis extract (CE).
[0106] For the viability of cancer cells compared to the cannabis
extract (CE), the CE was set at an index of 5, and the cancer cell
viability of MX2 to MX6 was evaluated as an index of 1 to 10. It
can be said to mean that the higher the index is, the smaller the
viability of cancer cells is.
TABLE-US-00002 TABLE 2 CE MX2 MX3 MX4 MX5 MX6 Suppression of
survival of 5 6 7 8 7 6 HCT116 cells Suppression of survival 5 5 6
6 6 5 of HT-29 cells (Unit: Index)
[0107] As shown in Table 2 above, it was confirmed that the complex
extracts MX2 to MX6 reduced the viability of cancer cells
equivalent to or higher than that of the cannabis extract (CE).
This can be said to mean that when the complex extract is used as a
natural complex extract, the effect of reducing the viability of
cancer cells is excellent due to the complex action of each
ingredient, compared to when only the cannabis extract (CE) is
used.
Experimental Example 2: Resistance Experiment
[0108] Cannabis Extract (CE)
[0109] After the cannabis extract (CE) was injected at a
concentration of 0 .mu.m, 10 .mu.m, 20 .mu.m, 30 .mu.m, 40 .mu.m,
50 .mu.m, and 100 .mu.m, respectively into liver cancer and gastric
cancer cell lines (SNU38M.RTM., AGS.RTM.) showing resistance to
celastrol which is an ingredient with anti-cancer action,
resistance was analyzed by MTT assay. As a result, as illustrated
in FIGS. 2 and 3, it was found that the cannabis extract (CE)
suppressed the resistance of each cancer cell line.
[0110] Complex Extract
[0111] In order to see whether complex extracts (MX2 to MX6) also
cause resistance of the cancer cell lines, the same experiment as
the resistance experiment of the cannabis extract (CE) was
performed, and the results thereof are shown in comparison with the
relative effect on cannabis extract (CE).
[0112] For the resistance of cancer cell lines compared to the
cannabis extract (CE), the CE was set at an index of 5, and the
cancer cell line resistance to MX2 to MX6 was evaluated as an index
of 1 to 10. It can be said to mean that the larger the index is,
the less resistant the cancer cell line is.
TABLE-US-00003 TABLE 3 CE MX2 MX3 MX4 MX5 MX6 SNU38M .RTM. 5 6 7 7
7 6 AGS .RTM. 5 5 5 6 7 6 (Unit: Index)
[0113] As shown in Table 3 above, it was confirmed that the complex
extracts MX2 to MX6 did not cause resistance of cancer cell lines
equivalent to or higher than that of the cannabis extract (CE).
This can be said to mean that when the natural complex extract is
used, the effect of suppressing the resistance of cancer cell lines
is excellent due to the complex action of each ingredient, compared
to when only the cannabis extract (CE) is used.
Experimental Example 3: Effect of Suppressing Cancer Metastasis
[0114] Cannabis Extract (CE)
[0115] In order to investigate the effects of the cannabis extract
(CE) on the enzymatic activity of MMP-2 and MMP-2 which are enzymes
essential for invasion and neovascularization of cancer cells
during cancer metastasis through gelatin degradation of the
extracellular matrix, the following experiment was performed.
[0116] First, for the activity of MMP-2 and MMP-9, the experiment
was performed by treating the colorectal cancer cells HCT116 cells
cultured in Experimental Example 1 with the cannabis extract (CE)
and treating the HCT116 cells with 1 ng/ml of PMA known to
stimulate the expression and activity of MMP-2 and MMP-9.
[0117] After HCT116 cells were treated with the cannabis extract
(CE), enzymatic activities of MMP-2 and MMP-9 were measured in the
supernatant cultured for 72 hours. As in FIG. 4, it was shown that
the cannabis extract (CE) reduced the activity of MMP-9 in a
concentration-dependent manner at 10 .mu.m or more compared to the
PMA-treated group. In addition, it was shown that the activity of
MMP-2, which is in an active form, was reduced at a concentration
of 30 .mu.m or more, and the activity was reduced by 50% compared
to the PMA-treated group at a maximum concentration of 100
.mu.m.
[0118] Complex Extract
[0119] In order to investigate the effect of suppressing the cancer
metastasis of the complex extracts (MX2 to MX6), the same
experiment as the experiment of the cannabis extract (CE) was
performed, and the results thereof are shown in comparison with the
relative effect on cannabis extract (CE).
[0120] For the effect of suppressing cancer metastasis compared to
the cannabis extract (CE), the CE was set at an index of 5, and the
effects of MX2 to MX6 on the suppression of the enzymatic
activities of MMP-2 and MMP-9 were evaluated as an index of 1 to
10. It can be said to mean that the higher the index is, the better
the effects of suppressing the cancer metastasis are.
TABLE-US-00004 TABLE 4 CE MX2 MX3 MX4 MX5 MX6 Suppression of
activity 5 6 7 8 7 6 of MMP-2 Suppression of activity 5 5 7 7 6 5
of MMP-9 (Unit: Index)
[0121] As shown in Table 4 above, it was confirmed that the complex
extracts MX2 to MX6 suppressed the enzymatic activities of MMP-2
and MMP-9 equivalent to or higher than that of the cannabis extract
(CE). This can be said to mean that when the natural complex
extract is used, the effect of suppressing the enzymatic activities
of MMP-2 and MMP-9 is excellent due to the complex action of each
ingredient, compared to when only the cannabis extract (CE) is
used.
Experimental Example 4: Preference Test
[0122] Sensory Evaluation Test
[0123] Tea beverages were prepared by diluting MX1 and the complex
extracts MX3 to MX6. The tea beverages were sampled by 10 tasters,
and the taste and aroma were expressed by an index of 1 to 10, and
the average values (applied to a rounding of 0.5) are shown in the
following Table 5. The higher the number of the index is, the
higher the preference is.
TABLE-US-00005 TABLE 5 MX1 MX2 MX3 MX4 MX5 MX6 Taste 6.0 6.0 6.5
7.0 7.0 6.0 Aroma 6.0 6.5 6.5 7.0 7.5 7.0 Overall preference 6.0
6.0 7.0 7.0 7.0 6.5 (average) (Unit: Index)
[0124] Referring to Table 5, it can be seen that in the case of
MX1, the unique taste and aroma reduced the preference using the
cannabis extract alone, and in the case of using the mixture of MX2
to MX6, the preference is enhanced while the taste and aroma
peculiar to the cannabis extract are neutralized by other natural
extracts. In particular, in the case of using MX3 to MX5, it was
confirmed that the aroma was highly evaluated and the preference
was also enhanced significantly.
[0125] Therefore, in the case of using the complex extracts MX3 to
MX5, it is possible to provide a functional food with higher aroma
and taste in terms of preference, which has excellent effects of
anti-cancer, reducing anti-cancer side effects, and suppressing
cancer metastasis.
[0126] While preferred embodiments of the present invention have
been described in detail hereinabove, it is to be understood that
the scope of the present invention is not limited thereto, and
various modifications and improvements made by those skilled in the
art using basic concepts of the present invention, which are
defined in the following claims also fall within the scope of the
present invention.
* * * * *