Note: Descriptions are shown in the official language in which they were submitted.
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An agent for treating and/or preventing osteoporosis,
comprising oceanic mineral components.
TECHNICAL FIELD
The present invention relates to an agent for
treating and/or preventing osteoporosis, comprising
oceanic mineral components. More specifically, the
invention relates to an agent for treating and/or
preventing osteoporosis, comprising as active ingredient
an oceanic mineral complex obtained by removing sodium
chloride and toxic components from concentrated seawater.
BACKGROUND ART
Recently, relationship between micromineral
deficiencies and aging has been attracting attention. The
reported similarities between aging symptoms and
micromineral deficiencies are shown in Table 1 below.
Table 1: Similarities between aging symptoms and micromineral
deficiencies
Aging symptoms Mineral type
deficiency in which
causes the same
symptom
= Decline in physical All minerals
strength/Devitalization
= Skin atrophy/Balding Zinc
= Poor wound healing Zinc
= Hypogonadism Zinc
= Reduced sense of taste/Loss of Zinc
appetite
= cataractogenesis Zinc
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= Reduced immune function Zinc, Copper,
and selenium
= Onset of depression/dementia Zinc and Copper
= ischemic heart disease Copper, selenium,
zinc and silicon
= autoimmune disease Zinc, copper, and
Selenium
= Cancer Zinc and selenium
= Abnormal glucose Chromium and zinc
tolerance/diabetes
Pathophysiologic factors in aging include
increases in active oxygen and free radicals, immune
compromise, circulatory system diseases such as elevation
in blood pressure and hyperlipidemia, abnormal glucose
tolerance and carcinogenesis. Deficiencies in many kinds
of minerals cause same clinical conditions. Especially,
free radicals are generated metabolic process in vivo and
become a cell-inhibiting factor inhibiting. It has been
revealed that increase in such free radicals is involved
in mechanisms of aging, life-style-related diseases, and
cancers. Generally, an enzyme which can convert such
radicals (SOD: superoxide dismutase) works to control
toxic actions. In case of micromineral deficiencies in
an aged living body, the action of this enzyme is
inhibited. In such a case, it is said that natural
defense mechanism gets out of order and the living body is
devitalized to become more likely to develop lifestyle-
related diseases. This is supported by the facts that
decrease in SOD enzymes can be redressed by addition of
microminerals and that conditions of lifestyle-related
diseases such as high blood pressure, hyperlipidemia and
diabetes can be improved by addition of microminerals,
which is experimentally evidenced. Also, it has been
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conventionally reported in epidemiologic researches that
selenium deficiency or zinc deficiency increases cancer
incidence. Thus, micromineral deficiencies are closely
related to aging and diseases.
In line with the aging of the society and
increasing population of elderly people, the number of
patients with osteoporosis is increasing. Osteoporosis
afflicts patients by confining them to bed, developing
dementia or the like. In osteoporosis, bone
resorption(destruction) by osteoclastic cells outpaces
bone formation by osteoblast cells. As a result, bone
mass decreases and bone becomes fragile. Osteoporosis is
roughly categorized into primary osteoporosis and
secondary osteoporosis. There is no particular disease
causing primary osteoporosis. Primary osteoporosis is
caused by dysfunction in bone formation or bone
resorption. Secondary osteoporosis is caused by other
diseases. It is known that hormone-related diseases such
as chronic renal failure, chronic articular rheumatism,
hyperthyroidism, hypogonadism and Cushing's syndrome,
diabetes, alimentary diseases and the like cause secondary
osteoporosis.
Primary osteoporosis is roughly divided into
postmenopausal osteoporosis and senile osteoporosis. In
case of female patients, a rapidly decline in female
hormone estrogen takes place before menopause occurs.
With this, a large amount of cytokine which promotes none
resorption (destruction) is produced, causing a rapid
decline in bone density. Moreover, estrogen has an effect
of converting vitamin D into activated vitamin D. Since
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activated vitamin D has an effect of promoting calcium
absorption into the intestine, a decrease in estrogen
disturbs absorption of calcium through the intestine and
becomes a factor reducing bone mass. Further, the older
one is, the more likely osteoporosis is to develop. In
case of senile osteoporosis, bone mass decreases due to
bone aging and kidney activity declines, which leads to
decrease in ability of synthesizing activated vitamin D
and decrease in bone mass.
As described above, in osteoporosis, bone mass
per volume, i.e. bone density, decreases, and bone becomes
light in weight and weak, which leads to easy fractures of
bones. That is, bone density increases until the age
around 30 when bone formation is more active than bone
resorption. After that, when bone formation in vivo
becomes insufficient, bone resorption outpaces bone
formation and bone density continues to decrease. In case
of female bodies, bone density peaks at the age of around
30, and then begins to gradually decrease. It is known
that from the age of around 50 when one reaches menopause,
decrease in density is accelerated.
It is easier to prevent bone density from
decreasing than to recover lost bone density. Therefore,
in osteoporosis, generally, prevention is more effective
than treatment. Methods for prevention or treatment
include appropriate intake of calcium or vitamin D,
weight-bearing exercise, and administration of drugs.
Among theses, prevention or treatment using drugs, which
is useful in maintaining bone density or retarding
decrease in bone density, is used in practice
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appropriately. Examples of drugs used for preventing or
treating osteoporosis include calcium agent, estrogen
agent, activated vitamin D3 agent, vitamin K2 agent,
bisphosphonate agent, phosphonate agent, ipriflavone
agent, protein anabolic hormone agent, and calcitonin
agent.
Calcium agent is expected to have effects in
those who lack calcium or in elderly people who do not eat
much. Practically, calcium agent is used in combination
with activated vitamin D3 agent, estrogen agent or the
like. When calcium agent is used, however, side-effects
such as gastrointestinal distress and astriction are often
observed. In cases where calcium agent is administered to
patients with hyperparathyroidism, a certain type of
kidney failure or hypercalcinuria, hypercalcemia may be
caused. Estrogen can act directly or indirectly on bones,
suppressing bone resorption and maintaining bone density.
Estrogen, however, has a problem that it causes menstrual
bleeding. For preventing this, care is needed to ingest
the agent. Although activated vitamin D3 agent enhances
absorption of calcium through the intestine and suppresses
decrease in bone mass, it is known to cause hypercalcemia
as side-effect. Vitamin K2 agent has an effect of
preventing bone fractures, and bisphosphonate agent
suppresses decrease in bone density. These agents,
however, sometimes cause gastrointestinal distresses as
side-effects. Ipriflavone agent, which is said to have
both effects of accelerating bone formation and
suppressing bone resorption, often causes gastrointestinal
distress. Protein anabolic hormone agent is recognized as
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having an effect of increasing bone density. Since it is
hormone-based agent, it has many side effects and care
must be taken in using the agent and patient types which
the agent may be used for are limited. Calcitonin agent
has an effect of suppressing bone resorption by
osteoclastic cells, to thereby suppress decrease in bone
density. Since the agent is administered intramuscularly,
the burden on the patient becomes too much if it is used
for a long term. Moreover, it is known that effects of
calcitonin are lessened if it is used for a long time.
DISCLOSURE OF INVENTION
PROBLEMS TO BE SOLVED BY INVENTION
As described above, there are often unignorable
side-effects or risks or heavy burdens on patients in
cases using conventional drugs for preventing or treating
osteoporosis. Moreover, even if one agent is necessary
for treating symptoms or clinical conditions of one
patient, the agent cannot be used for the patient in some
cases. The objective of the present invention is to
provide an agent for treating and/or preventing
osteoporosis effectively by using oceanic mineral
components which components contain essential trace
elements, which agent can solve or alleviate one or more
of the above problems in conventional agents.
MEANS FOR SOLVING THE PROBLEM
Generally, when one enters his middle-life, the
balance between microminerals in the body collapses due to
decreases in amounts of intake and absorption or disorders
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in metabolism or excretion process, which leads to chronic
deficiency in microminerals. Accordingly, intakes of
microminerals play an important role in maintaining health
and preventing diseases for people entering middle-age
generation.
Minerals springing from thermal deposits
existing in the sea bed and minerals flowing in from land
for 3.6 billion years since the earth was born are
dissolved in seawater. All the trace elements related to
aging symptoms as above described are contained in
seawater. Components constituting the blood or body fluid
flowing in the human body are said to be closely similar
with components of primordial sea water. It has been
already assumed that microminerals are essential elements
for cellular-level metabolism which supports life activity
of the living body.
Recently, developments have been made on
methods required for analyzing elements which exist at
only a low concentration in human body. Further,
functions of various trace elements have been brought out
by biochemical studies. Thus, essentiality of trace
elements in human body has been confirmed.
Main elements constituting the living body as
proteins, nucleic acids or blood are hydrogen (H), oxygen
(0), carbon (C), and nitrogen (N), and a small amount of
phosphorus(P) and sulfur(S) is also contained. Moreover,
elements constituting bone and body fluid are calcium
(Ca), Sodium (Na), Potassium (K), magnesium (Mg), and
chloride (Cl). Together with these major elements, there
are essential trace elements in the living body, such as
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iron (Fe), zinc (Zn), copper (Cu), arsenic (As), chromium
(Cr), cobalt (Co), selenium (Se), manganese (Mn),
molybdenum, silicon (Si), fluorine (F), vanadium (V),
nickel (Ni), tin (Sn), and iodine (I).
All of these essential trace elements are
transition elements whose charge states easily change.
Many of them act as enzymes which catalyze oxidation
reduction reaction where electrons are given or received
or as components for coenzymes in the living body.
Recently, functions of theses trace elements have been
clarified by finding that deficiencies in essential trace
elements such as chromium and zinc cause disorders in
sugar metabolism which requires insulin or in metabolism
of protein and nucleic acid(Saishin-Igaku,45,
808, (1990) ) . Also, as for diabetes, effects of sea water
minerals on diabetic mice have been confirmed by
experiments (Japan Medical Journal, Vol.3675, 1-Oct-1994).
The present inventors have made extensive
studies on how oceanic minerals contained in sea water act
in the living body and have already proposed an agent for
treating allergies comprising as an active ingredient a
mineral complex (Marina Calcium Mineral; hereinafter
abbreviated as MCM: a product of Kaiyo Kagaku Kenkyukai)
containing major elements and trace elements, which
complex is obtained by removing sodium chloride from
concentrated seawater as much as possible and then
removing toxic components such as mercury, which agent is
effective for treating hepatitis, high blood pressure,
tumor, atopic dermatitis, nasal inflammation and the like
(Japanese Patent No. 3247620).
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As for osteoporosis, conventional drugs
currently used for treating and/or preventing osteoporosis
have problems of side-effects, risks, administration
methods, burdens on patients and poor potentiality of
applying to various types of patients, as above described.
Moreover, the most important effect of increasing bone
mass by these drugs is not so great as desired and is in a
level that the bone mass does not decrease. The present
inventors have made extensive studies with a view to using
the above-mentioned mineral complex (MCM) containing major
elements and trace elements in an agent for treating
and/or preventing osteoporosis free from side-effects and
burdens on patients and essentially applicable to any
patient, and have found out that MCM can be expected to
increase bone mass and can be an effective agent for
treating and/or preventing osteoporosis.
EFFECTS OF INVENTION
The oceanic mineral complex (MCM) according to
the present invention contains trace elements essentially
required in the living body in addition to major elements
of calcium (Ca), sodium (Na), potassium (K) and magnesium
(Mg), which consist of components obtained by removing
toxic components such as sodium chloride and organic
mercury from concentrated seawater. The present invention
is excellent in that the agent for treating and/or
preventing osteoporosis can be administered basically to
all types of patients to sufficiently increase bone mass
without problems of side-effects and burdens on patients
and thus be effectively used for treating, preventing and
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improving the symptoms of the disease.
DETAILED DESCRIPTION
Hereinafter, the present invention is described
in detail.
[Production method of the mineral complex (MCM)
containing major elements and trace elements essentially
required in the living body]
The agent for treating and/or preventing
osteoporosis according to the present invention comprises
as the active ingredient the oceanic mineral complex (MCM)
consisting of residue containing chelated minerals
obtained by treating concentrated seawater containing
organic components derived from picoplanktons living in
seawater and mineral components chelated by the organic
components with acetic acid and removing sodium chloride
and toxic components therefrom. In the present invention,
the oceanic mineral complex can be prepared with calcium
which is required for bone formation contained in an
amount enhanced by adding calcium acetate to the
concentrated seawater containing the minerals to react
with each other. In a preferred embodiment, calcium
carbonate is calcined and then acetic acid is added
thereto to thereby convert it into calcium acetate. By
adding this to heated concentrated seawater, the oceanic
mineral complex can be prepared with an enhanced amount of
calcium required for bone formation. To concentrated
seawater containing the minerals, generally 10-30 %,
preferably 20 % of calcium carbonate is added in volume
ratio and the mixture is calcined generally at about 300-
500 C, preferably about 400 C. To this, generally 90-
100 %, preferably 98-99.9% grade acetic acid is added, to
convert it into calcium acetate. The resultant is added
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to the concentrated seawater heated generally at a heat
source temperature of about 100-200 C, preferably at
about 150 C. After reaction starts, the mixture is left
standing generally for about 24 to 120 hours, preferably
about 48 to 96 hours, more preferably about 72 hours, to
thereby complete the reaction calmly. It is preferable
that the amount of calcium required for bone formation
contained in the oceanic mineral complex be enhanced.
MCM, which is the active ingredient in the present
invention, is prepared, for example, by using as raw
material seawater pumped up from a clean seawater region
of about 80 to 120 meters deep under the sea. Table 2
shows main elements contained in 18 liters of sea water
which was pumped up from depth of about 100 meters under
the sea surface in a typical black current region (off
Oarai coast, Japan) and proportion.
Table 2 : Amount of each element contained in 18 L of
seawater sampled ( g)
Element Weight ( g )
Sodium (Na) 49,500,000
Magnesium (Mg) 6,125,000
Sulfur (S) 4,240,000
Potassium (K) 1,880,000
Calcium (Ca) 1,790,000
Carbon (C) 132,000
Silicon (Si) 14,130
Nitrogen (N) 2,350
Phosphorus (P) 330
Zinc (Zn) 150
Iron (Fe) 150
Chromium (Cr) 470
Selenium (Se) 14
This raw material seawater is heated under
normal pressure or reduced pressure, to thereby
concentrate it until the volume becomes reduced to about
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1/60 of the initial volume. Next, sodium chloride is
removed from this concentrated water as much as possible.
By adding 99 % grade acetic acid of the almost same volume
as the volume of the concentrated water and about 0.5 % by
weight of charcoal powder to the concentrated seawater,
heating the mixture to about 400 C and then cooling it to
-12 C, components containing sodium chloride mainly,
mercury and the like are solidified. This solid product
is filtered. To the obtained filtrate, the operations of
(1) adding acetic acid and charcoal powder, (2) heating
followed by cooling and (3) filtrating off solid matters,
in the same manner as described above, are repeated about
four times, to obtain a final filtrate. In the thus
obtained oceanic mineral complex (MCM) consisting of
residue solid product, components are chelated by
picoplanktons, which are organic components of seawater,
and MCM as is can be used in the agent for treating and/or
preventing osteoporosis.
Table 3 shows elements contained in 1 g of the
crystalline solid product (MCM) chelated by organic
substances present in seawater with sodium chloride and
toxic components having been removed therefrom. It is
preferred that in the agent for treating and/or preventing
osteoporosis, the crystalline solid powder (MCM)
containing minerals about 20 to 30 % by mass of organic
components derived from planktons, particularly preferably
about 25 % by mass.
Table 3: Major elements and trace elements contained in 1 g of M
CM
Components weight ( g)
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Water (H2O) 242,700
Sodium (Na) 54,300
Potassium (K) 81,600
Calcium (Ca) 310,500
Magnesium (Mg) 1,700
Organic substances
(C,H,O,S,P,N) 253,400
Chloride (Cl) 35,300
Silicon (Si) 125
Iron (Fe) 125
Copper (Cu) 8
Chromium (Cr) 250
Manganese (Mn) 10
Zinc (Zn) 60
Selenium (Se) 16
Cadmium (Cd) Not detected
Lead (Pb) Not detected
Organic mercury (Hg) Not detected
[Toxicity]
It has been confirmed that toxicity of the
oceanic mineral complex (MCM) according to the present
invention is so sufficiently low that it can be safely
used for medical purposes.
[Application to medical products]
The agent for treating and/or preventing
osteoporosis according to the present invention comprises
an oceanic mineral complex, MCM, which is residue
containing chelated minerals, obtained by subjecting
concentrated seawater containing organic components
derived from picoplanktons present in seawater and
minerals chelated by the organic components to treatment
with acetic acid and removing sodium chloride and toxic
components therefrom. The oceanic mineral complex (MCM)
according to the present invention is, as already known,
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effective when used in treating diabetes, hepatitis, high
pressure, tumor, atopic dermatitis, nasal inflammation
and other allergic diseases, and also in treating and
preventing osteoporosis. The oceanic mineral complex
(MCM) according to the present invention is used generally
by oral administration, for the purpose of
treating/preventing osteoporosis. The dosage amount
depends on age, weight, symptoms, target in
treatment/prevention, administration method,
administration time and so forth. Generally, a single
dose for adult is within a range of 300 to 400 mg and the
number of doses per day is 1 to several times.
When the oceanic mineral complex (MCM)
according to the present invention is administered, it is
prepared into a solid composition, liquid composition or
other forms for oral administration. Examples of solid
forms for oral administration include tablet, pill,
capsule, powder, and granule. Examples of liquid forms
for oral administration include opalizer, solution, syrup,
and elixir and may further contain inactive diluent (for
example, purified water and ethanol). In this
composition, adjuvants such as moisturizer and suspension
agent, and sweetening agent, flavor, fragrance, and/or
antiseptic may be contained.
EXAMPLE
Hereinafter, effects of the agent for treating
and preventing osteoporosis are explained based on
Example. The present invention is, however, by no means
limited to Example.
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Preparation of MCM:
18 L of clean seawater was sampled out from a
black current region (off Oarai coast, Japan) about 100
meters deep under the sea surface. (Components are shown
in Table 2). This was concentrated by heating and then
treated with charcoal powder and acetic acid. Sodium
chloride and components such as organic mercury which are
harmful to the living body were removed. The operation of
heating and removing by freezing was repeated, so that the
oceanic minerals were condensed and crystallized, to
thereby obtain a powdery solid (MCM) as shown in Table 3.
The above prepared MCM was orally administered
to a 80-year-old (male) patient during his treatment
period. His bone density values before treatment and
after treatment were compared. The results are shown in
Table 4. Table 4 also shows treatment results of a 74-
year-old (female) patient and healthy people of a 70-year-
old (male) and 69-year-old (female) Here, the values
shown by percent (%) are percentage when compared with the
average bone density of each age. The measurement on bone
density was made by using an X-ray bone density measurer
DTX-200 (manufactured by TOYO MEDIC CO., LTD.) for the 80-
year-old patient and the healthy 70-year-old (male) and
69-year-old (female) and by bone mineral quantitation
using X-ray for the 74-year-old (female) patient.
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Table 4
Patient's
age and Before treatment After treatment
sex
80 70% 75%
Measurement date: Measurement date:
(male) August 5, 2004 January 20, 2006
86%
74 76~ Measurement date: Measurement date:
(female) November 19, 2004 January 26, 2006
70 100%
(male) Measurement date: February 22, 2006
69 103%
(female) Measurement date: February 22, 2006
As seen in Table 4, the bone density of the 80-
year-old patient (male) increased by 5 %, from 70 %
(compared with the average bone density of the age) before
treatment to 75 % after treatment. Also, with respect to
the 74-year-old (female), her bone density increased by 10
%, from 76 % (compared with the average bone density of
the age) before treatment to 86 % after treatment.
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