Composition for alleviating, preventing or treating bone diseases, containing aster pseudoglehnii extract or fraction thereof as active component

Abstract

The present invention relates to a composition having the purpose of preventing, alleviating or treating bone-related diseases, the composition comprising an extract of Aster pseudoglehnii. The composition has the effects of promoting osteoblast differentiation and increasing bone density, and can be used as a composition for preventing, alleviating or treating bone diseases such as osteoporosis.

Description

Composition for improving, preventing or treating bone disease comprising an extract of Aster japonica or a fraction thereof as an active ingredient

[0001] The present invention relates to a composition having an improving, preventing or treating effect on bone-related diseases, comprising an extract of Aster pseudoglehnii or a solvent fraction thereof.

[0002] Osteoporosis is a disease characterized by decreased bone density and quality, weakening bones and increasing the risk of fractures. It's common for bone strength to decline with age, and osteoporosis is particularly prevalent in those over 50, experiencing menopause. Osteoporosis progresses rapidly in postmenopausal women, affecting one in three women in their 50s. This prevalence is due to the close relationship between postmenopausal hormone decline and bone health. While the incidence is lower in men, the risk of developing osteoporosis increases with age, affecting one in five men over 50.

[0003] Osteoporosis has a variety of causes, with known causes including calcium malabsorption, vitamin D deficiency, menopause, side effects from various medications, lack of exercise, and a family history. While there are no specific symptoms in the early stages, as osteoporosis progresses, the vertebrae become weakened, deformed, or compressed, leading to decreased height and a spinal distortion as the spine becomes unable to support body weight. Once osteoporosis develops, bone strength decreases, increasing the risk of fracture. In severe cases, bones can easily break even during everyday activities like bending over or coughing.

[0004] Osteoporosis treatment demand is increasing due to the growing elderly population, their increased leisure activities, and improved well-being. Various osteoporosis treatments are being developed. Symptoms can be improved or alleviated through the use of various hormones and calcium supplements. However, excessive hormone intake can cause side effects such as breast cancer, venous thrombosis, stroke, and gastrointestinal problems. Therefore, there is a pressing need to develop substances that can prevent or treat bone diseases like osteoporosis while minimizing side effects.

[0005] Accordingly, the inventors of the present invention conducted research to develop a substance that has a preventive or therapeutic effect on bone diseases such as osteoporosis and has reduced side effects, and in particular, while conducting research to develop a therapeutic ingredient derived from natural products, they confirmed that an extract of Aster pseudoglehnii can have activity for the prevention or treatment of bone diseases, and thus completed the present invention.

[0006] Accordingly, the purpose of the present invention is to provide a pharmaceutical composition for preventing or treating bone-related diseases comprising an extract or fraction of Aster pseudoglehnii.

[0007] Another object of the present invention is to provide a health functional food for preventing or improving bone-related diseases, comprising an extract or fraction of Aster pseudoglehnii.

[0008] Another object of the present invention is to provide a feed or feed additive composition comprising an extract or fraction of Aster pseudoglehnii.

[0009] Another object of the present invention is to provide a method for producing an extract or fraction having a preventive or therapeutic effect on bone-related diseases from Aster pseudoglehnii.

[0010] Another object of the present invention is to provide a method for preventing or treating bone disease by administering an extract or fraction of Aster pseudoglehnii to a subject other than a human.

[0011] In order to achieve the above purpose, the present invention provides a pharmaceutical composition for preventing or treating bone-related diseases, comprising an extract or fraction of Aster pseudoglehnii.

[0012] In order to achieve another object of the present invention, the present invention provides a health functional food for preventing or improving bone-related diseases, which contains an extract or fraction of Aster pseudoglehnii.

[0013] In order to achieve another object of the present invention, the present invention provides a feed or feed additive composition comprising an extract or fraction of Aster pseudoglehnii.

[0014] In order to achieve another object of the present invention, the present invention provides a method for producing an extract or fraction having a preventive or therapeutic effect on bone-related diseases from Aster pseudoglehnii.

[0015] In order to achieve another object of the present invention, the present invention provides a method for preventing or treating bone disease by administering an extract or fraction of Aster pseudoglehnii to a subject other than a human.

[0016]

[0017] Hereinafter, the present invention will be described in detail.

[0018] As one aspect of the present invention, the present invention relates to a composition for preventing, improving or treating bone-related diseases, comprising an extract or fraction of Aster pseudoglehnii.

[0019] The above island mugwort (Aster pseudoglehnii), also known as "bujiggaeng-inamul," is a perennial plant of the Asteraceae family, distributed in Ulleungdo Island and Pohang City in Gyeongsangbuk-do Province. The stem of the island mugwort grows to about 1 to 1.5 meters in height, and the leaves are oval or oblanceolate, 8 to 20 cm long, and have a pointed tip. The flowers bloom from August to September, are arranged in a single row in a tongue-like shape, and the corolla is white. The fruit is an achene with short hairs and a few glandular spots, and ripens in October to November. In oriental medicine, it is known to be effective for inflammation and asthma, and has been used as a medicinal herb, and is known to have effects such as anti-allergy and improving cognitive function.

[0020] In the present invention, the extract of Aster japonica may be extracted from the entire plant or from various organs contained in the plant, including above-ground or underground parts, such as roots, aerial roots, stems, leaves, and fruits. In one embodiment of the present invention, the extract was extracted by collecting the above-ground parts of Aster japonica, but is not limited thereto.

[0021] The island mugwort extract of the present invention can be extracted by any known extraction method, and is not limited thereto. The extraction method may be selected from any one or more extraction methods selected from the group consisting of reduced pressure high temperature extraction, hot water extraction, reflux extraction, hot water extraction, cold extraction, room temperature extraction, ultrasonic extraction, and steam extraction.

[0022] The above extract can use various solvents as extraction solvents, especially water, C 1-4 A lower alcohol or a mixed solvent thereof may be used, and specifically, water, ethanol, methanol, or a mixed solvent of water and ethanol may be selected and used, but is not limited thereto.

[0023] In addition, the extract of the present invention may include any one of an extract obtained by extraction treatment, a diluted or concentrated extract, a dried product obtained by drying the extract, or a controlled or purified product thereof.

[0024] Meanwhile, the Aster japonica fraction of the present invention can be obtained by fractionating from an Aster japonica extract, and more specifically, can be obtained by fractionating the Aster japonica extract using a solvent such as n-hexane, ethyl acetate, chloroform, or butanol. The fraction can be obtained by a method known in the art, for example, after suspending an Aster japonica ethanol extract in distilled water, adding a solvent such as n-hexane, ethyl acetate, chloroform, or butanol in an amount of about 1 to 100 times, specifically about 1 to 5 times, of the suspension, and extracting and separating the solvent-soluble layer 1 to 10 times, more specifically 2 to 5 times, to obtain a fraction.

[0025] In one embodiment of the present invention, the island mugwort extract is extracted with ethanol or a mixed solvent of water and ethanol, and the fraction may be a fraction obtained by fractionating the extract with n-hexane.

[0026] In the present invention, the Aster japonica extract or a fraction thereof has a preventive, therapeutic, or improving effect on bone-related diseases. The bone-related diseases are not limited in type, and may be, for example, one or more diseases selected from the group consisting of osteoporosis, fracture, periodontal disease, Paget disease, osteomalacia, osteopenia, bone atrophy, osteoarthritis, and metastatic bone cancers. The Aster japonica extract or fraction of the present invention promotes the differentiation of osteoblasts and has an effect of increasing bone density, thereby having a preventive, therapeutic, or improving effect on the above-mentioned bone diseases.

[0027] That is, the extract or fraction of the island mugwort of the present invention can be used for various purposes, such as pharmaceutical compositions, health functional food compositions, functional foods, animal feed, and cell culture compositions.

[0028] The term “prevention” in this specification means any action that can suppress or delay the onset of a bone-related disease by administering a pharmaceutical composition according to the present invention.

[0029] The term “treatment” as used herein refers to any action that improves or benefits the symptoms of a bone-related disease by administering the pharmaceutical composition according to the present invention.

[0030] The pharmaceutical composition of the present invention can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions according to conventional methods, and may additionally include carriers or excipients necessary for the formulation. Pharmaceutically acceptable carriers, excipients, and diluents that may be additionally included in the active ingredient include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, and mineral oil. When formulating, it is usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.

[0031] For example, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing the extract or compound with at least one excipient, such as cotton, starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.

[0032] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, Tween 61, cacao butter, laurin, and glycerogelatin.

[0033] The pharmaceutical composition of the present invention can be administered orally or parenterally (intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method, and the dosage varies depending on the patient's condition and weight, the degree of the disease, the drug form, the route of administration, and the time of administration, and can be selected in an appropriate form by a person skilled in the art.

[0034] The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, the term "pharmaceutically effective amount" means a reasonable amount applicable to medical treatment and an amount sufficient to treat a disease, and the standard thereof may be determined according to the patient's disease, severity, drug activity, drug sensitivity, administration time, administration route and excretion rate, treatment period, concomitantly used ingredients, and other factors. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with conventional therapeutic agents. The dosage may be determined at a level that can minimize side effects by taking all of the above factors into consideration, and this can be easily determined by a person skilled in the art. Specifically, the dosage of the pharmaceutical composition may vary depending on the patient's age, weight, severity, sex, etc., and generally, 0.001 to 150 mg per 1 kg of body weight, more preferably 0.01 to 100 mg, may be administered once to three times a day, daily or every other day. However, this is an example and the dosage may be set differently as needed.

[0035] In addition, the island mugwort extract of the present invention can be included in a food or health functional food composition, and in particular, the "health functional food" means a food manufactured and processed using raw materials or ingredients having functionality useful to the human body according to Act No. 6727 on Health Functional Foods, and "functionality" means consuming for the purpose of obtaining a useful effect for health purposes such as regulating nutrients for the structure and function of the human body or physiological action.

[0036] The food or health functional food of the present invention can be manufactured and processed into pharmaceutical dosage forms such as powders, granules, tablets, capsules, pills, suspensions, emulsions, syrups, or health functional foods such as tea bags, infusions, beverages, candies, jellies, and gums for the purpose of preventing and improving bone-related diseases.

[0037] The food or health functional food composition of the present invention can be used as a food additive and can be manufactured into a product alone or in combination with other ingredients. In addition, nutrients, vitamins, electrolytes, flavoring agents, colorants and enhancers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. can be included. The above ingredients can be used alone or in combination, and can be combined in appropriate amounts.

[0038] As another embodiment of the present invention, the present invention relates to a feed or feed additive composition comprising an extract or fraction of Aster japonica.

[0039] In the present invention, 'feed' means a substance that supplies organic or inorganic nutrients necessary for sustaining the life of an animal. The feed includes nutrients such as energy, protein, lipid, vitamins, and minerals required by animals such as livestock, and may be plant-based feed such as grains, roots, fruits, food processing by-products, algae, fiber, oils, starches, meal, and grain by-products, or animal-based feed such as proteins, inorganic substances, oils, minerals, oils, and single-cell proteins, but is not limited thereto.

[0040] In the present invention, 'feed additive' means a substance added to feed to improve animal productivity or health, and may further include, but is not limited to, amino acids, vitamins, enzymes, flavoring agents, silicates, buffers, extractants, oligosaccharides, etc. for growth promotion, disease prevention, etc.

[0041] The content of the island mugwort extract included in the feed or feed additive of the present invention is not particularly limited thereto, but may be 0.001 to 1% (w / w), preferably 0.005 to 0.9% (w / w), and most preferably 0.01 to 0.5% (w / w).

[0042] In another aspect of the present invention, the present invention relates to a method for producing an extract or fraction having a preventive or therapeutic effect on bone-related diseases from Aster pseudoglehnii, comprising the following steps.

[0043] 1) Step of washing, drying and crushing the Aster pseudoglehnii plant;

[0044] 2) A step of extracting by adding an extraction solvent to the crushed plant body;

[0045] 3) A step of removing the solvent from the above extract and concentrating under reduced pressure; and

[0046] 4) A step of fractionating the concentrated extract by adding one or more solvents selected from n-hexane, ethyl acetate, chloroform, and butanol.

[0047] The above manufacturing method can be performed using the extraction method and solvent described above, and the extract or fraction manufactured according to the above method contains an effective ingredient for preventing, improving, or treating bone-related diseases.

[0048] The present invention relates to a composition for the purpose of preventing, improving or treating bone-related diseases, comprising an extract of Aster pseudoglehnii, wherein the composition has the effect of promoting osteoblast differentiation and increasing bone density, and thus can be used for various purposes for the purpose of preventing, treating or improving various bone-related diseases such as osteoporosis.

[0049] Figure 1 shows the results of comparing the ALP activity of solvent-specific fractions of the island mugwort extract of the present invention.

[0050] Figure 2 shows the results of confirming the ALP activity of the n-hexane fraction of the island mugwort extract by concentration.

[0051] Figure 3 shows the results of comparing ALP activity of n-hexane fractions of various types of mugwort extracts.

[0052] Figure 4 shows the results of comparing the expression levels of osteoblast differentiation markers (RUNX2) in n-hexane fractions of various types of Artemisia princeps extracts.

[0053] Figure 5 shows the results of confirming the bone density increasing effect of the island mugwort extract of the present invention using a menopausal mouse model.

[0054]

[0055] In one aspect, the present invention relates to a pharmaceutical composition for preventing or treating bone-related diseases comprising an extract or fraction of Aster pseudoglehnii.

[0056] In another aspect, the present invention relates to a health functional food composition for preventing or improving bone-related diseases, comprising an extract or fraction of Aster pseudoglehnii.

[0057] The above bone-related disease may be one or more selected from the group consisting of osteoporosis, fracture, periodontal disease, Paget disease, osteomalacia, osteopenia, bone atrophy, osteoarthritis, and metastatic bone cancers.

[0058] In another aspect, the present invention relates to a feed or feed additive composition having a bone disease prevention or improvement effect, comprising an extract or fraction of Aster pseudoglehnii.

[0059] As an example, the island mugwort extract included in the composition includes one or more parts of the root, aerial root, stem, leaf or fruit of island mugwort.

[0060] As another example, the above-mentioned island mugwort extract may be extracted by an extraction method selected from the group consisting of reduced pressure high temperature extraction, hot water extraction, reflux extraction, hot water extraction, cold extraction, room temperature extraction, ultrasonic extraction, and steam extraction.

[0061] As another example, a composition wherein the above-mentioned island mugwort extract is extracted with water, a lower alcohol of C1-4, or a mixed solvent thereof.

[0062] As another example, the island mugwort extract may include any one of an extract, a diluted or concentrated extract, a dried product obtained by drying the extract, or a controlled or purified product thereof.

[0063] As another example, the island Aster fraction may be obtained by fractionating the island Aster extract with one or more solvents selected from n-hexane, ethyl acetate, chloroform, and butanol.

[0064] The island mugwort extract of the present invention may have an effect of promoting osteoblast differentiation or an effect of increasing bone density.

[0065] In another aspect, the present invention relates to a method for producing an Aster pseudoglehnii extract, comprising the steps of washing, drying, and crushing an Aster pseudoglehnii plant; extracting the crushed plant by adding an extraction solvent; removing the solvent from the extract and concentrating under reduced pressure; and fractionating the concentrated extract by adding at least one solvent selected from n-hexane, ethyl acetate, chloroform, and butanol.

[0066] In another aspect, the present invention relates to a method for preventing, improving or treating bone disease by administering an extract or fraction of Aster pseudoglehnii to a subject other than a human.

[0067]

[0068] Hereinafter, examples will be described in detail to specifically explain this specification. However, the embodiments according to this specification may be modified in various different forms, and the scope of this specification is not limited to the embodiments described below. The embodiments of this specification are provided to more fully explain this specification to those of average skill in the art.

[0069] Example 1. Preparation of island mugwort extract

[0070] The aerial parts (leaves, stems) of Aster pseudoglehnii were collected from Ulleungdo Island in May 2020, washed thoroughly with water, and dried in warm air (30°C) for 7 days to obtain dried plants.

[0071] The dried plant body was crushed into 20 mm pieces, placed in an extraction container, and a 70% ethanol / water mixture was added. The extraction was repeated twice for 7 days while shaking and stirring at room temperature. The mixture was gravity filtered using a Whatman paper filter with a film thickness of 0.34 mm and a glass funnel to obtain a filtered extract. The filtered extract was transferred to a round flask, placed in a vacuum concentrator, and concentrated by completely evaporating the solvent under reduced pressure at 35°C to obtain an Aster japonica extract (hereinafter referred to as AP1).

[0072] The above-mentioned Aster japonica extract (AP1) was suspended in water, 4 L of n-hexane was added, and fractionation was performed three times for 2 hours each while shaking and stirring at room temperature to obtain n-hexane fractions (BPAPW00002, AP2). The water remaining after the fractionation was subjected to fractionation three times for 2 hours each while adding 4 L of saturated n-butanol and shaking and stirring at room temperature to obtain n-butanol fractions (BPAPW00003, AP3). The water remaining after the fractionation (BPAPW00004, AP4) was freeze-dried and stored.

[0073] Experimental Example 1. Confirmation of the effect of promoting osteoblast differentiation.

[0074] 1-1) Effect of extracts and fractions on osteoblast differentiation promotion

[0075] After treating MC3T3-E1 pre-osteoblast cells with 40 μg / ml of the above extracts and fractions for 6 days, the cells were washed with phosphate-buffered saline (PBS) solution, and the cell membrane was lysed using 0.2% Triton X-100. The cells were centrifuged at 2,500×g, 4℃ for 15 minutes, and the supernatant was collected. ALP activity was measured from the supernatant using a SensoLyte p-nitrophenyl phosphate (p-NPP) ALP activity assay kit (AnaSpec, Inc., Fremont, CA, USA). The positive control group was treated with 40 μM Silymarin. ALP activity was expressed by comparing the differentiated cells with those calculated as 100%.

[0076] As a result, among the extracts and fractions of Aster japonica, the hexane fraction (AP2) was the most effective (Fig. 1), and this effect was confirmed to increase in a concentration-dependent manner (10–40 μg / ml). (Fig. 2)

[0077] 1-2. Comparison of the effects of promoting differentiation by species

[0078] An experiment was conducted to compare the osteoblast differentiation effect (ALP activity, differentiation marker expression) of the Asteraceae fraction prepared in Example 1 and other species of Asteraceae fractions.

[0079] In the same manner as in Example 1, fractions of Aster altaicus var. uchiyamae, Aster incisus, Aster ageratoides, and Aster pilosus were prepared. 40 μg / ml of each fraction prepared above was treated on MC3T3-E1 pre-osteoblasts for 6 days. The cells were washed with phosphate buffered saline (PBS), the cell membrane was lysed using 0.2% Triton X-100, and the cells were centrifuged at 2,500×g, 4℃ for 15 minutes to obtain the supernatant. The ALP activity of the supernatant was measured using a SensoLyte p-nitrophenyl phosphate (p-NPP) ALP activity assay kit (AnaSpec, Inc., Fremont, CA, USA). The positive control group was treated with 40 μM of Silymarin. ALP activity was expressed by comparing differentiated cells with 100%.

[0080] As a result, as shown in Fig. 3, it was confirmed that Aster japonica showed high osteoblast differentiation ability compared to the positive control group, whereas other Aster japonica species did not have this activity.

[0081] In addition, in order to confirm the osteoblast differentiation promoting effect of the above fractions at the gene expression level, MC3T3-E1 pre-osteoblast cells were treated with 40 μg / ml of each fraction for 6 days, and the cells were washed with PBS (phosphate buffered saline) solution. RNA was obtained and cDNA was synthesized to compare the expression level of the RUNX2 gene, an osteoblast differentiation marker. As a result, as shown in Fig. 4, it was confirmed that only Aster japonica increased the expression of the RUNX2 gene, an osteoblast differentiation marker, compared to the positive control group.

[0082]

[0083] Experimental Example 2. Effect of increasing bone density

[0084] In order to confirm whether the Artemisia capillaris fraction prepared in Example 1 above increases bone density in an animal model of menopausal osteoporosis through ovariectomy, the following experiment was conducted.

[0085] Seven-week-old C57BL / 6J female mice were purchased and acclimated for one week, after which bilateral ovariectomy was performed under anesthesia. In addition, the negative control group (Sham) underwent abdominal resection and suturing without ovarian removal, followed by a two-week recovery period. Both the experimental and control groups were orally administered 10 mg / kg or 40 mg / kg of Aster japonica fraction for 10 weeks, and the positive control group (E+P) was administered 0.1 mg / kg β-estradiol and 1 mg / kg progesterone to promote bone density changes through hormonal regulation. After 12 weeks, the femur bones of mice in each group were measured using Micro CT to confirm changes in bone density.

[0086] As a result, as shown in Fig. 5, bone density was significantly reduced in the ovariectomized group (OVX), and bone density in the positive control group was confirmed to have increased compared to the ovariectomized group. On the other hand, bone density was confirmed to have significantly increased in the group treated with the Aster japonica fraction compared to the ovariectomized group or the positive control group.

[0087] Through this, it was confirmed that the Artemisia princeps extract promotes differentiation of osteoblasts, inhibits bone density loss, and has the effect of treating osteoporosis, one of the representative diseases of menopausal syndrome.

[0088]

[0089] The present invention has been described above, focusing on preferred embodiments thereof. Those skilled in the art will appreciate that the present invention can be implemented in modified forms without departing from its essential characteristics. Therefore, the disclosed embodiments should be considered illustrative rather than restrictive. The scope of the present invention is set forth in the claims, not the foregoing description, and all differences within the scope equivalent thereto should be construed as being encompassed by the present invention.

Claims

1. A pharmaceutical composition for preventing or treating bone-related diseases containing an extract or fraction of Aster pseudoglehnii.

2. In paragraph 1, The above island mugwort extract is a pharmaceutical composition obtained by extracting one or more parts of the roots, aerial roots, stems, leaves or fruits of island mugwort using water, lower alcohol of C1-4 or a mixed solvent thereof.

3. In paragraph 1, A pharmaceutical composition, wherein the above-mentioned island mugwort fraction is obtained by fractionating an island mugwort extract with one or more solvents selected from n-hexane, ethyl acetate, chloroform, and butanol.

4. In paragraph 1, A pharmaceutical composition, wherein the bone-related disease is at least one disease selected from the group consisting of osteoporosis, fracture, periodontal disease, Paget disease, osteomalacia, osteopenia, bone atrophy, osteoarthritis, and metastatic bone cancers.

5. In paragraph 1, A pharmaceutical composition wherein the above-mentioned island mugwort extract has an effect of promoting osteoblast differentiation or increasing bone density.

6. A health functional food composition for preventing or improving bone-related diseases, comprising an extract or fraction of Aster pseudoglehnii.

7. In paragraph 6, The above island mugwort extract is a health functional food composition obtained by extracting one or more parts of the roots, aerial roots, stems, leaves or fruits of island mugwort using water, lower alcohol of C1-4 or a mixed solvent thereof.

8. In paragraph 6, A health functional food composition, wherein the above-mentioned island mugwort fraction is obtained by fractionating an island mugwort extract with one or more solvents selected from n-hexane, ethyl acetate, chloroform, and butanol.

9. In paragraph 6, A health functional food composition, wherein the bone-related disease is at least one disease selected from the group consisting of osteoporosis, fracture, periodontal disease, Paget disease, osteomalacia, osteopenia, bone atrophy, osteoarthritis, and metastatic bone cancers.

10. In paragraph 6, A health functional food composition in which the above-mentioned island mugwort extract has the effect of promoting osteoblast differentiation or increasing bone density.

11. An animal feed or composition for animal feed additive having a bone disease prevention or improvement effect, comprising an extract or fraction of Aster pseudoglehnii. 12.1) Step of washing, drying and crushing the Aster pseudoglehnii plant; 2) A step of extracting by adding an extraction solvent to the crushed plant body; 3) A step of removing the solvent from the above extract and concentrating under reduced pressure; and 4) A method for producing an extract or fraction of Aster japonica having a preventive, improving or therapeutic effect on bone disease, comprising a step of fractionating the concentrated extract by adding one or more solvents selected from n-hexane, ethyl acetate, chloroform and butanol.

13. A method for preventing, improving or treating bone disease by administering an extract or fraction of Aster pseudoglehnii to a non-human subject.

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