KR102230498B1 - Composition containing h2-occluded calcium for the treatment of osteoporosis - Google Patents

Abstract

Hydrogenstoring calcium composition for osteoporosis according to the present invention is calcium carbonate (CaCO _3), or calcium hydrogen (H ₂₎ is storing a combined calcium baking is water hydrogenstoring potassium carbonate (CaO) oxide (CaCO ₃ · H ₂₎ fired product Or hydrogen-occluded calcium oxide (CaO·H ₂ ) contains calcined material, and has a remarkable effect on the fundamental treatment of osteoporosis, and in particular, has the effect of curing osteoporosis induced in patients with ovarian hypofunction.

Description

Composition containing hydrogen-occluded calcium for osteoporosis treatment {COMPOSITION CONTAINING H2-OCCLUDED CALCIUM FOR THE TREATMENT OF OSTEOPOROSIS}

The present invention relates to a hydrogen-occluded calcium-containing composition for the treatment of osteoporosis, and more specifically, hydrogen (H ₂ ) containing an occluded calcium calcined product to determine the bone density and cortical bone content of patients with osteoporosis when ingested. It increases and decreases the content of ALP, osteocalcin, PIN1, TRAP 5b and OPG in the blood, and particularly relates to a hydrogen-occluded calcium-containing composition for treating osteoporosis capable of treating osteoporosis in patients with osteoporosis caused by ovarian hypofunction. .

In relation to osteoporosis, in the past, research has been mainly focused on abnormalities in the metabolism of bone minerals, that is, calcium and phosphorus, and no progress has been made in the investigation of its pathogenesis. However, in recent years, the importance of research on the metabolism of bone matrix proteins as well as minerals important for bone formation is emerging.

Osteoporosis, rather than itself, is a variety of fractures that are easily caused by weakening of the bone, especially femur fractures or vertebral fractures, which limit long-term activities, making it impossible to lead a healthy life and consequently account for about 15% of the causes of death in the elderly. It is emerging as a serious problem in that it occupies.

Bone tissue is a dynamic tissue that is formed by osteoblasts and destroyed and absorbed by osteoclasts. There are many uncertainties in the mechanism of bone resorption and formation, but osteoporosis is a disease caused by an increase in bone resorption than bone formation. Osteoporosis is caused by a breakdown of the balance between bone resorption and bone formation.

On the other hand, the following Patent Document 1 contains an initial composition of at least 22.75% by weight extracted from a calcium-containing source or a synthetic calcium acetate-containing source, the initial composition is strengthened by magnesium and zinc to at least 4% by weight of calcium, at least 5% by weight. % Magnesium, at least 0.2% by weight of zinc, and at least 400 IU of vitamin D3. In particular, there is a limit to the treatment and improvement of osteoporosis in patients with osteoporosis caused by deterioration of the ovaries due to various ovarian diseases and the like.

On the other hand, it is reported that calcium adjuvants, which are widely applied as osteoporosis treatments, do not show any substantial effect on the fundamental treatment of osteoporosis.

Accordingly, there is an urgent need to develop a new composition that shows a substantial effect on the fundamental treatment of osteoporosis, and can effectively treat osteoporosis caused in particular in patients with ovarian hypofunction.

Patent Document 1: Republic of Korea Patent Publication No. 10-2010-0107468 (2010.10.05)

The present invention has been made to solve the above problems, and an object of the present invention is to provide a composition that shows a substantial effect on the fundamental treatment of osteoporosis, and in particular, can effectively treat osteoporosis induced in patients with ovarian hypofunction.

One osteoporosis hydrogenstoring calcium composition in accordance with an embodiment of the present invention is calcium carbonate (CaCO ₃₎ or hydrogen (H ₂₎ is storing a combined calcium baking is water hydrogenstoring calcium carbonate to calcium oxide (CaO) oxide (CaCO ₃ · H ₂ ) Fired products or hydrogen-occluded calcium oxide (CaO·H ₂ ) fired products are included.

The hydrogen-occluded calcium composition for treating osteoporosis according to an embodiment of the present invention is characterized in that it increases the bone density and the content of cortical bone in osteoporosis patients.

The hydrogen-occluded calcium composition for osteoporosis treatment according to an embodiment of the present invention is calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin, and procollagen 1 in the blood of osteoporosis patients. N-terminal propeptide (procollagen 1 N-terminal propeptide, P1NP), tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteoprotegenin (OPG) It is characterized by that.

The hydrogen-occluded calcium composition for treating osteoporosis according to an embodiment of the present invention has a formulation of a tablet, a jelly, a powder having an average particle diameter of 10 to 200 μm, or a granule having an average particle diameter of 0.5 to 2 mm, and the powder Alternatively, the composition of the granule formulation may be embedded in ingestable soft capsules or hard capsules, or may be embedded in packaging materials other than capsules.

The hydrogen-occluded calcium composition for treating osteoporosis according to an embodiment of the present invention is characterized in treating osteoporosis in patients with osteoporosis caused by ovarian decline.

The hydrogen-occluded calcium composition for treating osteoporosis according to an embodiment of the present invention is a first calcined body by calcining at least one organic calcium carbonate selected from the group consisting of egg shell calcium, pearl calcium, shell calcium, and seaweed calcium. 1 firing step; And a second firing step of firing the first fired body under a hydrogen atmosphere to prepare a second fired body.

In the method for preparing a hydrogen-occluded calcium composition for treating osteoporosis according to an embodiment of the present invention, in the first firing step, the organic calcium carbonate is fired at 300 to 1,000° C. for 2 to 10 hours to obtain a first calcined body. It is performed as a process of manufacturing, and the second firing step is characterized in that it is carried out as a process of producing a second fired body by firing the first fired body at 300 to 1,000°C for 2 to 10 hours in a hydrogen atmosphere.

The hydrogen-occluded calcium composition for the treatment of osteoporosis according to the present invention has a substantial effect on the fundamental treatment of osteoporosis, and in particular, has an effect capable of treating osteoporosis induced in patients with ovarian hypofunction.

1 is a photograph observed under a microscope after performing H&E staining by tissue treatment of a femur having a reduced function for the histomorphological observation of the femur.

Before describing the present invention in more detail, terms or words used in the specification and claims are not to be limited to their usual or dictionary meanings, and the concept of terms is appropriate to describe the invention in the best way. It should be interpreted as a meaning and concept consistent with the technical idea of the present invention on the basis of the principle that it can be defined. Therefore, the configuration of the embodiment described in the present specification is only one preferred example of the present invention, and does not represent all the technical spirit of the present invention, and various equivalents and modifications that can replace them at the time of the present application It should be understood that there may be.

The present invention relates to a composition containing hydrogen-occluded calcium for the treatment of osteoporosis, and more specifically, to a patient having osteoporosis when administered in the body through ingestion or the like by containing a calcium calcined product in which _{hydrogen (H 2) is occluded.} For the treatment of osteoporosis, which can increase the bone mineral density and cortical bone content of, and at the same time reduce the content of ALP, osteocalcin, PIN1, TRAP 5b and OPG in the blood, and in particular treat osteoporosis in patients with osteoporosis caused by ovarian hypofunction. It relates to a hydrogen-occluding calcium-containing composition.

In the process of performing various experiments using the hydrogen-containing material registered in Patent No. 10-1405431, the present inventors have discovered a completely unexpected effect of the hydrogen-containing material registered in Patent No. 10-1405431.

That is, the present inventors accidentally discovered that the hydrogen-containing substance registered in Patent No. 10-1405431 is effective in improving bone metabolism in patients with osteoporosis, and in particular, has an excellent effect in improving osteoporosis caused by ovarian function decline. .

The calcium calcined product contained in the composition for treating osteoporosis of the present invention is completely different from the conventional calcium preparation, and is prepared through the following process.

That is, the calcium calcined product included in the composition for treating osteoporosis of the present invention is a first calcined body by calcining at least one organic calcium carbonate selected from the group consisting of egg shell calcium, pearl calcium, shell calcium, and seaweed calcium. 1 firing step; And a second firing step of firing the first fired body under a hydrogen atmosphere to prepare a second fired body.

Meanwhile, the first firing step is performed by firing the organic calcium carbonate at 300 to 1,000°C for 2 to 10 hours to prepare a first fired body, and in the second firing step, the first fired body is converted to hydrogen. It is carried out in the process of producing a second fired body by firing for 2 to 10 hours at 300 to 1,000 ℃ in the atmosphere.

Through this high-temperature sintering process, hydrogen (H ₂ ) is inserted and bound (occluded) calcium sintered product is prepared, and the inventors of the present invention have thus obtained hydrogen (H ₂ ) occluded and bound (occluded) calcium sintered product through the following experiment. It was discovered by chance that this osteoporosis can be remarkably improved, and in particular, osteoporosis caused by a decrease in ovarian function can be effectively treated, and accordingly, the hydrogen content of Patent No. 10-1405431 can be used as an effective composition for treating osteoporosis. I found it.

Hydrogenstoring calcium composition for osteoporosis according to the present invention is calcium carbonate (CaCO ₃₎ or hydrogen in the calcium oxide (CaO) oxide (H ₂₎ the adsorption of calcium baking is water hydrogenstoring calcium binding (CaCO ₃ · H ₂₎ fired product or Contains hydrogen-occluded calcium oxide (CaO·H ₂ ) calcined material.

As described above, the calcium sintered product used in the present invention is manufactured through a high-temperature sintering process.

On the other hand, the hydrogen storage calcium composition for treating osteoporosis of the present invention is characterized in that it increases the bone density and the content of cortical bone in osteoporosis patients.

That is, when the composition of the present invention is administered to a patient with osteoporosis by a method such as oral administration, the bone density of the femur is remarkably improved and the content of the cortical bone of the femur is also remarkably increased.

On the other hand, the composition of the present invention is calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin, procollagen 1 N-terminal propeptide (procollagen 1 N) in the blood of osteoporosis patients. -terminal propeptide, P1NP), tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteoprotegenin (OPG) content.

In other words, these proteins are directly related to bone metabolism, and the higher the content of these substances in the blood, the worse the bone metabolism, resulting in symptoms of osteoporosis.

For example, the high content of calcium and phosphorus in the blood means that these components are dissolved in the bone and are introduced into the blood in large quantities, and in the end, these substances that contribute to the increase of bone density in the bone are insufficient in the bone. It is to do.

Meanwhile, the water-absorbing calcium composition of the present invention may be prepared as a tablet, jelly, powder having an average particle diameter of 10 to 200 μm, or granules having an average particle diameter of 0.5 to 2 mm, and the like, and the powder or granule It is also possible to prepare the composition of the formulation in a form that is embedded in ingestable soft capsules or hard capsules, or in packaging materials other than capsules.

The hydrogen-occluded calcium composition for treating osteoporosis according to the present invention comprises: a first firing step of firing at least one organic calcium carbonate selected from the group consisting of egg shell calcium, pearl calcium, shell calcium, and seaweed calcium to prepare a first fired body; And a second firing step of firing the first fired body in a hydrogen atmosphere to prepare a second fired body.

More specifically, the first firing step is performed by firing the organic calcium carbonate at 300 to 1,000°C for 2 to 10 hours to prepare a first fired body, and the second firing step is performed by the first firing body Is calcined at 300 to 1,000° C. for 2 to 10 hours in a hydrogen atmosphere to prepare a second calcined body.

The present inventors accidentally discovered that the composition of the present invention has a substantial therapeutic effect, particularly for osteoporosis caused by ovarian decline.

Hereinafter, an experiment performed to evaluate the effect of improving bone metabolism of the water-absorbing calcium composition of the present invention will be described in detail.

In order to evaluate the effect of improving bone metabolism of the hydrogen-occluded calcium composition according to the present invention, the present inventors conducted an experiment by using an animal model that caused osteoporosis by deteriorating ovaries.

More specifically, in order to evaluate the bone metabolism improvement effect of the hydrogen-occluded calcium calcined product (TA) according to the present invention in an in vivo (in vivo) system, the present inventors treated ICR mice that induce osteoporosis by degrading the ovary for 8 weeks. After oral administration of the test substance (ovarian decline at 6 weeks of age, oral administration of the test substance from 12 to 20 weeks of age), indices related to bone metabolism such as bone density were evaluated.

[Test substance]

Test substances (TA, TB) were prepared as follows.

TA: hydrogen storage calcium according to the present invention

TB: calcined calcium oxide

Hydrogen to calcium carbonate (CaCO ₃₎ or calcium oxide (CaO) contained in the treatment of osteoporosis hydrogenstoring calcium composition of the invention (H ₂₎ is occluded combined (occluded) calcium baking is water hydrogenstoring calcium carbonate (CaCO ₃ · H ₂ ) The calcined product and hydrogen-occluding calcium oxide (CaO·H ₂ ) The calcined product is the first calcined material by calcining at least one organic calcium carbonate selected from the group consisting of egg shell calcium, pearl calcium, shell calcium, and seaweed calcium. A first firing step of manufacturing; And a second firing step of firing the first fired body under a hydrogen atmosphere to prepare a second fired body, and the first firing step includes the organic calcium carbonate at 300 to 1,000° C. It is carried out as a process of producing a first fired body by firing for 10 hours, and the second firing step is to prepare a second fired body by firing the first fired body at 300 to 1,000°C for 2 to 10 hours in a hydrogen atmosphere It can be carried out as a process.

_{More specifically, hydrogen (H 2} ) is occluded and bonded to _{calcium carbonate (CaCO 3} ) or calcium oxide (CaO) contained in a hydrogen storage calcium-containing composition for relieving hangovers having a function of decomposing alcohol and acetaldehyde in the body according to the present invention. (occluded) Calcium calcined product, hydrogen-occluded calcium carbonate (CaCO ₃ · H ₂ ) calcined product and hydrogen-occluded calcium oxide (CaO·H ₂ ) calcined product can be prepared through the method disclosed in Patent No. 10-1405431.

Hydrogen storage calcium used in the experiments described later was prepared using oyster shells.

[Animal testing approval and ethics regulations]

All animal model experiments for evaluating the effect of improving bone metabolism of the hydrogen-occluded calcium composition of the present invention were performed according to the animal experiment regulations under the approval of the Animal Experimental Ethics Committee of Hallym University (Hallym 2018-50).

[Test animal and test substance administration]

Seven-week-old, ovarian hypofunction ICR mice without specific pathogen free were purchased and used from Dooyeol Biotech. After a one-week quarantine and adaptation process, healthy animals without weight loss were selected and used in the experiment. Experimental animals were reared in a breeding environment set with a temperature of 23 ± 3 ℃ relative humidity of 50 ± 10%, ventilation cycles 10-15 times/hour, lighting time 12 hours (08:00-20:00), and illumination 150-300Lux. During the acclimation period, the experimental animals were allowed to freely consume solid feed for experimental animals (Cargill Agripurina) and drinking water.

After a 1-week adaptation period, healthy animals without weight loss were selected, and healthy animals without weight loss were classified into 5 test groups based on the egg mass method. In other words, (G1) normal (sham-operation) control, (G2) ovariectomy control, (G3) ovarian hypofunction + 100 mg/kg body weight (BW) TA administration group, (G4) ovarian function Reduction + 300 mg / kg BW TA administration group, (G5) ovarian hypofunction + 300 mg / kg BW TB administration group were classified as shown in Table 1, respectively.

G1 G2 G3 G4 G5 Decreased ovarian function - + + + + Test substance - - 100mg/kgBW TA 300mg/kgBW TA 300mg/kgBW TB The number of experimental animals 10 10 10 10 10

Each test group used each of 10 experimental animals. In order to induce osteoporosis, they were reared for 4 weeks without administration of the test substance, and each test substance was then administered orally at a constant time every day for 8 weeks. During the test period, the diet was supplied with AIN-93G diet (Research Diets Inc.), and diet and drinking water were freely consumed.

The body weight of the experimental animals in each test group was measured at intervals of one week until the end of the test, using the test group classification date as one day.

[Blood collection and serum separation]

Experimental animals were fasted for 12 hours before sacrifice, and then tribromoethanol was anesthetized using an anesthetic prepared by diluting tribromoethanol with tertiary amylalcohol, and blood was collected from the orbit. Blood was placed in a serum separate tube (Becton Dickinson), left at room temperature for 30 minutes, centrifuged at 3,000 rpm for 20 minutes to separate the serum, and stored at -70°C until analysis.

[Measurement of femur bone density]

After blood collection on the day of autopsy, the femur was deteriorated to remove muscles, ligaments and fat attached to the skeleton, and then bone mineral density (BMD) of the femur was measured using a bone density meter (PIXImusTM, GE LUVAR).

[Histological observation of femur]

The femur was immersed in 4% Paraform Aldehyde Solution (PFA, Biosesang Co.) and fixed for 24 hours. After fixation, it was immersed in Calci-Clear Rapid (national diagnostics, Inc.) for 24 hours to demineralize, and the tissue was treated according to the general tissue processing procedure, embedded in paraffin, and cut to a thickness of 10 μm to make a section. . Hematoxylin & eosin (H&E) (Sigma-Aldrich, Co.) staining was performed according to a general method, and histomorphological changes of the femur were observed with an optical microscope (Zeiss).

[Biochemical analysis of components contained in blood]

Use a blood biochemical analyzer (KoneLab 20 XT, Thermo Fisher Scientific) to measure the content of alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P) in the serum using a blood biochemical analyzer (KoneLab 20 XT, Thermo Fisher Scientific). It was measured.

[Analysis of protein levels related to bone metabolism in serum]

Serum osteocalcin, osteoprotegenin (OPG), cross-linked N-terminal telopeptide of type I collagen (NTX), tartrate-resistant acidic force The content of phatase 5b (tartrate-resistant acid phosphatase 5b, TRAP 5b) and procollagen 1 N-terminal propeptide (P1NP) was suggested by the manufacturer using an ELISA kit (Elabscience Biotechnology Inc.). It was measured according to one method.

[Statistics processing]

All analytical values are expressed as mean±SEM. The collected results were analyzed using the GraphPad Prism 5.0 (GraphPad software) program. To compare the difference between the test substance administration group and the control group, Student's t-test and one-way analysis variance (ANOVA) were used. It was judged to be statistically significant only when p<0.05 or more.

[Influence on the body weight of experimental animals]

The test group was classified as day 0, and the body weight (g) of the experimental animals was measured at 1 week intervals, and is shown in Table 2 below.

[Table 2]

(Values are expressed as mean±SEM.)

( ^* p <0.05, ^** p <0.01, ^*** p <0.001 significantly different from that of G1 group)

( ^# p <0.05, ^## p <0.01, ^### p <0.001 significantly different from that of G1 group)

As can be seen from the results of Table 2, the weight of all experimental animals during the pre-test period normally increased over time. The weight of the ovarian hypofunction control group (G2) significantly increased at 4 weeks, 5 weeks, and 6 weeks compared to the normal control group (G1) subjected to sham-operation, but tended to increase during other periods, but had a significant effect. I didn't see it. Compared to the other test groups, the individual difference between the ovarian hypofunction control group (G2) was large, and it was judged that there was no statistical significance from that of the normal control group (G1). After the 5th week of supplying the test substance, the body weight of the test substance administration group (G3, G4, G5) showed a tendency to decrease compared to the ovarian hypofunction control group (G2), but there was no significant difference (Table 2). This suggests that the test substance does not affect the body weight of the experimental animal.

[Bone density of the femur]

At the end of the test, animals were sacrificed to degrade the femur to measure the bone mineral density (BMD) of the femur, and the results are shown in Table 3 below.

[Table 3]

(Values are expressed as mean±SEM.)

( ^* p <0.05, ^** p <0.01, ^*** p <0.001 significantly different from that of G1 group)

( ^# p <0.05, ^## p <0.01, ^### p <0.001 significantly different from that of G1 group)

As can be seen from the results of Table 3, the bone density of the femur (left + right) of the normal control group (G1) subjected to sham-operation was 0.096 ± 0.002 g/cm ^2, and the femur of the ovarian hypofunction control group (G2) Bone mineral density was 0.085 ± 0.001 g/cm ^2, and the femur bone density of the ovarian hypofunction control group (G2) was significantly reduced compared to the normal control group (G1). This indicates that the decrease in bone density was induced by ovarian function decline. The test substance administration group showed a tendency to increase the bone density of the femur compared to the ovarian hypofunction control group (G2), and in particular, the femur bone density of the 300mg/kg BW TA administration group (G4) was significantly compared to the ovarian hypofunction control group (G2). Increased.

[Histological observation of femur]

For histomorphological observation of the femur, the functionally degraded femur was subjected to H&E staining by tissue treatment, and the results are shown in FIG. 1. Compared to the normal control group (G1), the ovarian hypofunction control group (G2) had a decreased cortical bone and an increase in cancellous bone, and the overall tissue showed a porous, non-dense structure. Although the histomorphological difference of the femur according to the test substance was not large, an increase in cortical bone was observed in the 300mg/kg BW TA administration group (G4) compared to the ovarian hypofunction control group (G2) (FIG. 1).

[Ca and P content in serum]

In order to investigate the effect of the test substance on the mineral homeostasis in the body, the content of Ca and P in the blood was measured, and the results are shown in Table 4 below.

[Table 4]

(Values are expressed as mean±SEM.)

( ^* p <0.05, ^** p <0.01, ^*** p <0.001 significantly different from that of G1 group)

( ^# p <0.05, ^## p <0.01, ^### p <0.001 significantly different from that of G1 group)

As can be seen from the results of Table 4, the Ca content in the serum was significantly increased in the ovarian hypofunction control group (G2) compared to the normal control group (G1), and that of the test substance administration groups (G3, G4, G5). The Ca content in serum showed a tendency to decrease compared to that of the ovarian hypofunction control group (G2), but there was no significant difference. The P content in serum was significantly increased in the ovarian hypofunction control group (G2) compared to the normal control group (G1). Serum P content of the 100 mg/kg BW TA administration group (G3) and the 300 mg/kg BW TA administration group (G4) was significantly decreased compared to that of the ovarian hypofunction control group (G2) (Table 4).

[ALP activity in serum]

The ALP activity in the serum of G1 to G5 was measured, and the results are shown in Table 5 below.

[Table 5]

(Values are expressed as mean±SEM.)

( ^* p <0.05, ^** p <0.01, ^*** p <0.001 significantly different from that of G1 group)

( ^# p <0.05, ^## p <0.01, ^### p <0.001 significantly different from that of G1 group)

ALP is an enzyme secreted by osteoblasts and is an important indicator of bone formation by reflecting the activity of osteoblasts. It has been reported that when osteoporosis is induced due to ovarian decline, bone replacement increases and the activity of osteoblasts increases, leading to an increase in serum ALP.

As can be seen from the results of Table 5, serum ALP activity was significantly increased in the ovarian hypofunction control (G2) compared to the normal control (G1). Serum ALP activity in the test substance administration group (G3, G4, G5) showed a tendency to decrease compared to the ovarian hypofunction control group (G2), and in the 300 mg/kg BW TA administration group (G4), in the ovarian hypofunction control group (G2). It was significantly reduced compared to (Table 5).

[Bone metabolism related protein content in serum]

First, as a protein having specificity for bone and dentin, the content in the serum of osteocalcin and P1NP, which are important indicators of bone formation, was measured by reflecting the activity of osteoblasts and was made in osteoblasts, and is shown in Table 6 below.

[Table 6]

(Values are expressed as mean±SEM.)

( ^* p <0.05, ^** p <0.01, ^*** p <0.001 significantly different from that of G1 group)

( ^# p <0.05, ^## p <0.01, ^### p <0.001 significantly different from that of G1 group)

As can be seen from the results of Table 6, the contents of osteocalcin and P1NP were significantly reduced in the ovarian hypofunction control (G2) compared to the normal control (G1). The content of osteocalcin in serum was significantly increased in the test substance 300 mg/kg BW TA administration group (G4) compared to the ovarian hypofunction control group (G2) (Table 6).

Next, the serum contents of NTX and TRAP 5b, which are representative markers of bone resorption, were measured and shown in Table 7.

[Table 7]

(Values are expressed as mean±SEM.)

( ^* p <0.05, ^** p <0.01, ^*** p <0.001 significantly different from that of G1 group)

( ^# p <0.05, ^## p <0.01, ^### p <0.001 significantly different from that of G1 group)

As can be seen from the results of Table 7, NTX and TRAP 5b contents were significantly increased in the ovarian hypofunction control group (G2) compared to the normal control group (G1). The content of NTX in serum was significantly decreased in the 300 mg/kg BW TB administration group (G5). The content of TRAP 5b in serum was significantly decreased in all test groups (G3, G4, G5) compared to the ovarian hypofunction control group (G2) (Table 7).

On the other hand, OPG, a marker for inhibiting osteoclasts, was significantly decreased in the ovarian hypofunction control group (G2) compared to the normal control group (G1). The serum OPG content of the 300 mg/kg BW TA administration group (G4) was significantly decreased compared to the ovarian hypofunction control group (G2).

As a result of comprehensively evaluating the experimental results shown in Tables 2 to 7 and FIG. 1, the bone density of the femur was significantly reduced in the ovarian hypofunction control group (G2) compared to the sham-operated normal control group (G1). Serum Ca content, serum P content, serum ALP activity, serum NTX content, and serum TRAP 5b content of the ovarian hypofunction control group (G2) were significantly increased compared to the normal control group (G1), and the serum osteocalcin content and serum P1NP content were Compared to the normal control group (G1), it was significantly decreased in the ovarian hypofunction control group (G2). This indicates that the osteoporosis animal model is properly constructed by ovarian function decline.

On the other hand, administration of 100 mg/kg BW TA did not affect bone metabolism in the osteoporosis animal model of ovarian hypofunction. When 300 mg/kg BW TA was administered (G4), the bone mineral density, serum osteocalcin and serum osteoprotegenin content of the femur increased compared to the ovarian hypofunction control group (G2), and the serum P content, serum ALP activity, and serum TRAP 5b content were ovarian. It was significantly decreased in the 300 mg/kg BW TA administration group (G4) compared to the hypofunction control group (G2).

The above results indicate that administration of a high content (300 mg/kg BW) of hydrogen-containing calcium (TA) for a long time (8 weeks) has an effect on improving bone metabolism in an animal model of osteoporosis with ovarian hypofunction.

Claims (7)

As a hydrogen-occluded calcium composition for treating osteoporosis,
The composition is calcium carbonate (CaCO ₃ ) or calcium oxide (CaO) and hydrogen (H ₂ ) is a calcium calcined product in which hydrogen (H 2) is occluded and bonded to a hydrogen-occluded calcium carbonate (CaCO ₃ · H ₂ ) calcined product or hydrogen-occluded calcium oxide (CaO·H ₂ ) Including a fired product,
Calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin, procollagen 1 N-terminal propeptide (P1NP) in the blood of osteoporosis patients, It reduces the content of tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteoprotegenin (OPG),
The calcium calcined product is
A first firing step of firing at least one organic calcium carbonate selected from the group consisting of egg shell calcium, pearl calcium, shell calcium, and seaweed calcium to prepare a first fired body; And
It is produced through a second firing step of firing the first fired body in a hydrogen atmosphere to prepare a second fired body,
The first firing step is performed by firing the organic calcium carbonate at 300 to 1,000°C for 2 to 10 hours to prepare a first fired body,
The second firing step is performed by firing the first fired body at 300 to 1,000° C. for 2 to 10 hours in a hydrogen atmosphere to prepare a second fired body. The method according to claim 1,
The composition is a hydrogen-occluded calcium composition for treating osteoporosis, characterized in that to increase the bone mineral density and the content of cortical bone in osteoporosis patients. delete The method according to claim 1,
The composition has a formulation of tablet, jelly, powder having an average particle diameter of 10 to 200 μm, or granules having an average particle diameter of 0.5 to 2 mm,
The composition of the powder or granule formulation is a hydrogen-occluded calcium composition for treating osteoporosis that is embedded in ingestable soft capsules or hard capsules, or embedded in packaging materials other than capsules. The method according to claim 1,
The composition is a hydrogen-occluded calcium composition for treating osteoporosis, characterized in that it treats osteoporosis of a patient with osteoporosis caused by ovarian decline. delete delete

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