KR20200135187A - Composition comprising extract of Abeliophyllum distichum for prevention or treatment of bone diseases - Google Patents

Abstract

The present invention relates to a composition for preventing or treating bone diseases containing an Abeliophyllum distichum extract as an active component. More specifically, the present invention relates to a pharmaceutical composition and health functional food for preventing or treating bone diseases containing an Abeliophyllum distichum extract as an active component. The Abeliophyllum distichum extract according to the present invention has excellent activity to inhibit the differentiation or formation of osteoclasts, has no cytotoxicity, and has stability in the body by not causing side effects, thereby being able to be usefully used for manufacturing medicines and health functional food for preventing, treating, and alleviating various bone diseases caused by abnormal bone metabolism.

Description

Composition comprising extract of Abeliophyllum distichum for prevention or treatment of bone diseases}

The present invention relates to a composition for the prevention or treatment of bone disease, comprising the extract of Misun tree as an active ingredient.

Bone (bone) is a calcified connective tissue that is associated with a muscle, and its surface is a thick and hard calcified tissue that acts as a support to balance the body and protects organs. The inside of the bone is the bone marrow tissue, which is the center of calcium metabolism. Bone is composed of organic substances such as collagen, osteocalcin, and osteonectin, and inorganic substances such as calcium, phosphorus, and fluorine, and water. In the living body, bone formation and bone resorption (bone resorption) are always occurring. Bone formation is promoted by a small amount of parathyroid hormone, androgens, estrogen, fluorine, and phosphorus, and bone resorption is promoted by physical decompression, weightlessness, large amounts of parathyroid hormone, adrenal cortical steroids, and the like. Therefore, the balance between them is important for bone metabolism. Therefore, bone homeostasis is continuously controlled and maintained by bone resoprtion by osteoclast and bone remodeling by the equal action of bone formation by osteoblast. do.

It is known that two types of cells are largely involved in the process of bone remodeling, that is, remodeling. One of the two cells is an osteoblast that produces bone, and the other is an osteoclast that destroys bone. Osteoblasts produce RANKL (receptor activator of NF-κB ligand) and its decoy receptor, OPG (osteoprotegerin). When RANKL binds to RANK (receptor activator of NF-κB), a receptor on the surface of osteoclast progenitor cells, osteoclast progenitor cells differentiate into osteoclasts and bone resorption occurs. Specifically, the expression of nuclear factor of activated T cells (NFAT), which is known as a key transcription factor that regulates the differentiation of osteoclasts from osteoclast progenitor cells, is induced by transduction of intracellular calcium signals by RANKL stimulation, followed by extracellular signal regulation. Activation of extracellular signal-regulated kinase (ERK), NF-κB, and p38 MAP kinase induces autoamplification of NFAT and continues its activity. Therefore, the absorption or destruction of old bone is performed by osteoclasts through the above mechanism, which makes a hole in the bone and releases a small amount of calcium into the bloodstream, which is used to maintain body functions.

In addition, osteoblasts fill the pores with collagen and cover the calcium and phosphorus deposits (hydroxyapatite) to make new hard bones and rebuild the skeleton. In the case of adults, about 10-30% of the skeleton is reformed through this process every year, and the same bone density can be maintained only when the osteotomy speed and the osteoblast speed are the same. In normal adults, there is always a balance between the amount of bone resorption and the amount of bone formation. When the balance of such important bones is broken, many diseases can be caused, and these diseases are called bone diseases.

On the other hand, recently, in order to minimize the side effects of bone disease treatments, new bones that are less toxic and can minimize bone loss and promote bone formation by using natural materials such as foods and medicinal plants that can be eaten in daily life. Although research on disease prevention or treatment substances is being attempted in various ways, there have been no attempts on the possibility of use as a therapeutic agent for bone diseases in Misun trees until now.

Korean Patent Registration No. 10-1627705

Accordingly, the present inventors prepared extracts of Miseon tree and analyzed whether they inhibited osteoclast differentiation. As a result, as a result of confirming that Miseon tree extract had excellent inhibition of osteoclast differentiation, the possibility of use as a new therapeutic agent for bone disease was identified. Thus, the present invention was completed.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating bone diseases, comprising an extract of Misun tree as an active ingredient.

Another object of the present invention is to provide a health functional food for the prevention or improvement of bone disease, comprising the extract of Misun tree as an active ingredient.

In order to achieve the object of the present invention as described above, the present invention provides a pharmaceutical composition for the prevention or treatment of bone disease, comprising the extract as an active ingredient.

In one embodiment of the present invention, the extract may be a leaf extract of Misun tree.

In one embodiment of the present invention, the extract is a solvent selected from the group consisting of water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane. It may be obtained by using.

In one embodiment of the present invention, the extract may be to inhibit the differentiation or formation of osteoclasts.

In one embodiment of the present invention, the bone disease is osteoporosis, facet bone disease, rickets, osteomalacia, renal bone dystrophy in patients with renal failure, rheumatic bone disease, degenerative bone disease, bone metastatic lesion, primary It may be selected from the group consisting of tumors, periodontal disease, inflammatory alveolar bone resorption disease, and inflammatory bone resorption disease.

In addition, the present invention provides a health functional food for the prevention or improvement of bone disease, comprising the extract of Misun tree as an active ingredient.

In one embodiment of the present invention, the extract may be a leaf extract of Misun tree.

In one embodiment of the present invention, the extract is a solvent selected from the group consisting of water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane. It may be obtained by using.

In one embodiment of the present invention, the extract may be to inhibit the differentiation or formation of osteoclasts.

In one embodiment of the present invention, the bone disease is osteoporosis, facet bone disease, rickets, osteomalacia, renal bone dystrophy in patients with renal failure, rheumatic bone disease, degenerative bone disease, bone metastatic lesion, primary It may be selected from the group consisting of tumors, periodontal disease, inflammatory alveolar bone resorption disease, and inflammatory bone resorption disease.

Miseon tree extract according to the present invention has excellent activity to inhibit the differentiation or formation of osteoclasts, has no cytotoxicity, and does not cause side effects, so it has stability in the body, thus preventing, treating and improving various bone diseases caused by abnormal bone metabolism. It can be usefully used in the manufacture of medicines and health functional foods for the purpose of.

1 is a schematic diagram showing a process of obtaining an extract by using each portion of the fruit, stem, and leaves of the Miseon tree in an embodiment of the present invention.
Figure 2 shows the results of analyzing the osteoclast differentiation inhibitory activity and cytotoxicity of the methanol extract for each portion of the misun tree in an embodiment of the present invention.
Figure 3 shows the osteoclast differentiation inhibitory activity for each type of solvent in an embodiment of the present invention on the leaf extract of Misun tree.

The present invention is characterized in that it has identified a new use of the Misun tree extract capable of preventing or treating bone diseases by effectively inhibiting the formation of osteoclasts.

The Miseon (Abeliophyllum distichum) is a plant that grows naturally in Korea, and is known for its anti-cancer activity, atopic treatment efficacy, and anti-hair loss, but many studies have not been conducted yet.

Therefore, research is needed to reveal the various efficacy of our resource, Misun trees, and to actively reproduce and utilize them.

Accordingly, the inventors of the present invention were studying the useful effects of the Miseon tree, for the first time, by identifying that the extract of Miseon tree has an activity of effectively inhibiting the differentiation of osteoclasts, thereby preventing or preventing bone diseases containing the Miseon tree extract as an active ingredient. It was confirmed that it can be used for therapeutic purposes.

In the present invention, the "osteoblast" refers to a cell that destroys a bone matrix and plays a role of decomposing bone minerals, thereby performing a tissue destruction and absorption function. It has been reported that the osteoclasts can cause bone disease when an imbalance with osteoblasts occurs in the bone.

The “osteoblasts” are cells that make bone cells of vertebrates, originating from mesenchymal stem cells, and mineralization such as calcium formation by differentiation of osteoblasts not only maintains the strength of the bone, but also maintains the body's calcium and It also plays a very important function in the homeostasis of hormone metabolism. Calcium formation by osteoblast differentiation is regulated by vitamin D and parathyroid hormone, and bone formation by osteoblast differentiation is bone morphogenetic protein (BMP), Wnt, MAP in cells. Alkaline phosphatase related to osteoblast differentiation by cross-talk of various signaling systems such as kinase, calcineurin-calmodulin kinase, NF-κB, AP-1, etc. It is known that phosphatase (ALP) is synthesized in the initial differentiation stage, and then mineralization-related osteopontin, osteocalcin, and type 1 collagen are synthesized. Therefore, when abnormalities in the differentiation and formation of osteoblasts occur, problems in bone formation occur and bone diseases are caused.

As such, when the balance of the interaction between the osteoclasts and the osteoclasts is broken, a systemic or local bone disease is caused, and these diseases are known to be mostly due to an increase in the number and activity of osteoclasts.

Therefore, if the formation and differentiation of osteoclasts are inhibited, bone diseases caused by osteoclasts can be prevented or treated.

In addition, in another embodiment of the present invention, as a result of confirming the efficacy of the extract for each part of the Miseon tree with respect to the osteoclast differentiation inhibitory activity of the Miseon tree extract, the leaves of Miseon tree are superior to the stem and fruit extracts. It has been shown to have differentiation inhibitory activity.

Therefore, the present invention provides a pharmaceutical composition for the prevention or treatment of bone disease, comprising the extract of Misun tree as an active ingredient.

In the present invention, the bone disease to be prevented, improved or treated with the extract of Miseon trees is a disease that can be caused by an imbalance in the interaction between osteoblasts and osteoclasts, and any disease that can be caused by excessive differentiation and activity of osteoclasts. It may include, but is not limited to, osteoporosis, facet bone disease, rickets, osteomalacia, renal bone dystrophy, rheumatic bone disease, degenerative bone disease, bone metastatic lesion, primary bone It may include tumors, periodontal disease, inflammatory alveolar bone resorption disease, and inflammatory bone resorption disease.

In addition, the extract according to the present invention may be obtained by extracting and separating from nature using a method for extracting and separating known in the art, and the extract defined in the present invention may be used as a misun tree extract using an appropriate solvent. It is extracted from, and includes, for example, all of the crude extract, polar solvent-soluble extract, or non-polar solvent-soluble extract.

As a suitable solvent for obtaining the extract from Misun tree, any organic solvent may be used as long as it is a pharmaceutically acceptable organic solvent, and water or an organic solvent may be used, but is not limited thereto, for example, purified water, methanol (methanol), ethanol (ethanol), propanol (propanol), isopropanol (isopropanol), butanol (butanol), including alcohols having 1 to 4 carbon atoms, acetone, ether, benzene, chloroform Various solvents, such as (chloroform), ethyl acetate, methylene chloride, hexane, and cyclohexane, may be used alone or in combination. Methanol can be preferably used.

As the extraction method, any one of methods such as hot water extraction, cold precipitation extraction, reflux cooling extraction, solvent extraction, steam distillation method, ultrasonic extraction method, elution method, and compression method may be used. In addition, the desired extract may be further subjected to a conventional fractionation process, or may be purified using a conventional purification method.

In another embodiment of the present invention, in order to obtain an extract having the best osteoclast differentiation inhibitory activity in relation to the osteoclast differentiation inhibitory effect on the extract of Misen tree leaves, extracts were obtained using various solvents and the efficacy was analyzed. Was performed, and it was found that the use of methanol compared to other types of solvents had the best osteoclast differentiation inhibitory activity.

Therefore, through these results, the present inventors have obtained an extract obtained by adding methanol to the leaves of Miseon tree, that is, useful components derived from Miseon tree leaves contained in the extract can effectively inhibit the differentiation of osteoclasts. It was found that it can be most usefully used as a new treatment for disease.

The pharmaceutical composition of the present invention may be prepared by using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient of the present invention as a pharmaceutical composition comprising the extract of the present invention as an active ingredient, Excipients, disintegrants, sweeteners, binders, coating agents, expanding agents, lubricants, lubricants or flavoring agents may be used as the auxiliary agent.

For administration, the pharmaceutical composition may include one or more pharmaceutically acceptable carriers in addition to the active ingredient of the present invention, and may be preferably formulated into a pharmaceutical composition.

The formulation form of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, lacquercanth or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like. As acceptable pharmaceutical carriers for compositions formulated as liquid solutions, sterilization and biocompatible, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets. Further, it can be preferably formulated according to each disease or ingredient using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

Miseon tree extract of the present invention may be included in a concentration of 1 to 100 ㎍ / ㎖ in the composition of the present invention, and also the misun tree extract of the present invention may be included in 0.1 to 95% by weight based on the total weight of the composition.

In addition, the composition of the present invention may be a food composition, and the food composition may contain various flavoring agents or natural carbohydrates as an additional component, such as a conventional food composition, in addition to containing the active ingredient, Misun tree extract.

Examples of the above-described natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-described flavoring agents can be advantageously used as natural flavoring agents (taumatin), stevia extracts (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).

The food composition of the present invention can be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements, etc. There is this.

In addition, the food composition includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring and natural flavoring agents, coloring agents and thickeners (cheese, chocolate, etc.), pectic acid and its Salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like may be contained. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juice and fruit juice beverages and vegetable beverages.

As the active ingredient of the present invention, Misun tree extract is a substance extracted from natural materials and has almost no side effects, it can be safely used even when taken for a long time.

In addition, the present invention provides a health functional food for the prevention or improvement of bone disease comprising the extract as an active ingredient.

The health functional food of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and pills.

In the present invention, the term "health functional food" refers to a food manufactured and processed using raw materials or ingredients having useful functions for the human body according to the Health Functional Food Act No.6727, and nutrients for the structure and function of the human body It refers to ingestion for the purpose of controlling or obtaining beneficial effects for health purposes such as physiological effects.

The health functional food of the present invention may contain ordinary food additives, and whether it is suitable as a food additive is determined according to the general rules and general test methods for food additives approved by the Food and Drug Administration, unless otherwise specified. It is judged according to standards and standards.

Items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as reduced pigment, licorice extract, crystalline cellulose, high color pigment, and guar gum; Mixed preparations, such as a sodium L-glutamate preparation, an alkali additive for noodles, a preservative preparation, and a tar color preparation, etc. are mentioned.

For example, in the health functional food in the form of a tablet, a mixture of the active ingredient of the present invention, Misun tree extract, mixed with an excipient, a binder, a disintegrant, and other additives, is granulated by a conventional method, and then a lubricant is added. Compression molding, or the mixture may be directly compression molded. In addition, the health functional food in the form of a tablet may contain a mating agent or the like, if necessary.

Among the health functional foods in the form of capsules, hard capsules can be prepared by filling a conventional hard capsule with a mixture of the active ingredient of the present invention, which is the active ingredient of the present invention, mixed with additives such as excipients. It can be prepared by filling a mixture mixed with an additive such as an excipient in a capsule base such as gelatin. The soft capsules may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.

Ring-shaped health functional foods can be prepared by molding a mixture of the active ingredient of the present invention, excipients, binders, disintegrants, etc. by conventionally known methods, and can be coated with white sugar or other coating agents if necessary, Alternatively, the surface may be coated with a material such as starch or talc.

The health functional food in the form of granules can be prepared in granular form by a mixture of the active ingredient of the present invention, excipients, binders, disintegrants, etc., by a known method, and may contain flavoring agents, flavoring agents, etc. have.

The health functional food comprising the extract of Misun tree of the present invention as an active ingredient has excellent activity of inhibiting differentiation and formation of osteoclasts, and is effective in preventing or improving bone diseases.

The health functional food may be beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements.

Hereinafter, the present invention will be described in more detail through examples. These examples are for explaining the present invention more specifically, and the scope of the present invention is not limited to these examples.

<Example 1>

Preparation of extracts for each part of Misun tree

In order to obtain the extract for each part of the Miseon tree, the leaves, stems and fruits of the freeze-dried Miseon tree (50 g for each part) were extracted three times at room temperature for 6 hours each using methanol. Thereafter, the methanol extract for each site was filtered using Whatman filter paper, and the remaining solids were separated, and the filtered extract was concentrated under reduced pressure using a vacuum concentrator at 40°C to obtain a methanol extract for each site. A schematic diagram of the process is shown in FIG. 1.

<Example 2>

Analysis of the inhibitory effect of osteoclasts on the extracts of each part of Misun tree

The present inventors analyzed the effect of inhibiting osteoclasts on the extracts of each part of the Misun tree obtained in Example 1, that is, the methanol extract of leaves, stems and fruits.

For this purpose, 6-week-old male C57BL/6 mice were euthanized using 100% CO ₂ gas, and then the femur and tibia were separated. After cutting both ends of the separated tibia and femur, cells in the bone marrow cavity were collected with a 1 mL syringe, and red blood cells were dissolved and removed using a red blood cell lysis buffer (RBCL). Subsequently, the obtained bone marrow cells were cultured for 3 days in α-MEM medium containing 10% FBS and M-CSF (30 ng/mL). After 3 days of culture, the attached cells were used in the experiment as bone marrow-derived macrophages (BMMs). Specifically, after dispensing BMMs cells into a 48-well plate, RANKL (100 ng/ml) was added to induce differentiation into osteoclasts. In this process, the methanol extract of each portion of the present invention was treated at each concentration (0.1, 1, 10 μg/ml), and TRAP staining analysis was performed after 3 days.

As a result, as shown in Fig. 2, it was found that the fruit extract of Misun tree did not affect the differentiation of osteoclasts compared to the extracts of other parts, and leaves and stems were found to have an effect on the differentiation of osteoclasts. However, in the case of stem extract, it was found that cytotoxicity was induced and cells were killed.

On the other hand, it was found that only leaf extract of Misun tree can effectively inhibit osteoclasts without causing cytotoxicity.

Therefore, through these results, the inventors of the present invention believe that the fruit and stem extracts do not have osteoclast differentiation inhibitory activity in the case of the stem, and the stem may cause a problem of toxicity, so that the fruit and stem extracts are difficult to use as a material for treating bone diseases. It was confirmed that there is.

On the other hand, it was confirmed that the leaf extract of Misun tree could effectively inhibit the differentiation of osteoclasts without cytotoxicity, so that only the leaf extract of Misun tree could be safely used as a material for a new therapeutic agent for bone disease.

<Example 3>

Analysis of the Inhibitory Effect of Osteoclasts on the Extracts of Different Solvents from Leaves of Sunflower Tree

Through the results of Example 2, the present inventors found that the use of the leaves of the Miseon tree as a treatment for bone diseases using Miseon trees is most useful. Accordingly, the present inventors analyzed the osteoclast differentiation inhibitory activity of the extract obtained by changing the solvent in the process of obtaining the extract for the leaves of the Misen tree.

Specifically, in the process of Example 1, using ethylacetate, hexane, and butanol, which are other solvents in addition to methanol, for the leaves of Miseon tree to obtain a leaf extract of Miseon tree for each solvent. In the same manner as in the experiment of Example 2, an experiment for inhibiting osteoclast differentiation was performed.

As a result, as shown in FIG. 3, it was found that the methanol extract of the misen tree leaf had the best osteoclast differentiation inhibitory activity compared to the misun tree leaf extract obtained using ethanol, ethyl acetate, hexane and butanol.

Therefore, it was found that it is very important to select and use methanol as an extraction solvent to effectively inhibit the differentiation of osteoclasts.

So far, the present invention has been looked at around its preferred embodiments. Those of ordinary skill in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative point of view rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope equivalent thereto should be construed as being included in the present invention.

Claims (10)

A pharmaceutical composition for the prevention or treatment of bone disease, comprising an extract of Misun tree as an active ingredient. The method of claim 1,
The extract is a pharmaceutical composition for the prevention or treatment of bone disease, characterized in that the leaf extract of the Miseon tree. The method of claim 1,
The extract is characterized in that it is obtained using a solvent selected from the group consisting of water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane, A pharmaceutical composition for preventing or treating bone diseases. The method of claim 1,
The extract is characterized in that to inhibit the differentiation or formation of osteoclasts, a pharmaceutical composition for preventing or treating bone diseases. The method of claim 1,
The bone diseases are osteoporosis, facet bone disease, rickets, osteomalacia, renal bone dystrophy in patients with renal failure, rheumatic bone disease, degenerative bone disease, bone metastatic lesions, primary tumors in the bone, periodontal disease , Inflammatory alveolar bone resorption disease and inflammatory bone resorption disease, characterized in that selected from the group consisting of, a pharmaceutical composition for the prevention or treatment of bone disease. Health functional food for the prevention or improvement of bone disease, comprising the extract of Misun tree as an active ingredient. The method of claim 6,
The extract is a health functional food for the prevention or improvement of bone disease, characterized in that the leaf extract of Miseon tree. The method of claim 6,
The extract is characterized in that it is obtained using a solvent selected from the group consisting of water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane, Health functional food for preventing or improving bone disease. The method of claim 6,
The extract is a health functional food for preventing or improving bone disease, characterized in that it inhibits the differentiation or formation of osteoclasts. The method of claim 6,
The bone diseases are osteoporosis, facet bone disease, rickets, osteomalacia, renal bone dystrophy in patients with renal failure, rheumatic bone disease, degenerative bone disease, bone metastatic lesions, primary tumors in the bone, periodontal disease , Health functional food for preventing or improving bone disease, characterized in that selected from the group consisting of inflammatory alveolar bone resorption disease and inflammatory bone resorption disease.

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