KR20200056237A - Pharmaceutical composition for preventing or treating osteoporosis containing azelaic acid as an active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating osteoporosis containing azelaic acid as an active component. The pharmaceutical composition according to the present invention increases the expression level of Dlx5, Runx2, and OC, which are osteoblast differentiation marker genes, to have an effect of promoting the differentiation of osteoblasts, thereby being able to be widely used as medicines or health food for preventing or treating osteoporosis. In addition, the pharmaceutical composition promotes bone formation by increasing the activity of osteoblasts rather tan targeting osteoclasts, thereby being able to fundamentally treat osteoporosis and exhibit a secondary fracture prevention effect.

Description

Pharmaceutical composition for preventing or treating osteoporosis containing azelaic acid as an active ingredient}

The present invention relates to a pharmaceutical composition for preventing or treating osteoporosis containing azelaic acid as an active ingredient.

Recently, as various industrial accidents and traffic accidents have increased and aging society has increased, diseases of the musculoskeletal system due to osteoporosis and fractures have increased. For the prevention and treatment of such bone diseases, various types of bone grafting agents for inducing bone regeneration ability and new types of related disease treatment agents for improving osteoclast activity and reducing osteoclast activity have been developed. In addition, various studies have been attempted using stem cells and osteoblasts to actively induce new bones that can fill in areas with severe bone tumors and bone defects.

The bone remodeling process is a process in which old bones are periodically converted into new bones, and this process proceeds through steps such as proliferation, differentiation, and induction of extracellular matrix calcification. In general, the process of bone formation and absorption in adults is balanced by the interaction of osteoblasts derived from mesenchymal stem cells and osteoclasts derived from hematopoietic stem cells, thereby maintaining bone health. When there is an imbalance in activity between osteoblasts and osteoclasts, such as increased osteoclast activity or increased bone resorption, there is no significant change in tissue chemical composition, but bone mass decreases, resulting in bone metabolic diseases such as osteoporosis. Can be.

Osteoporosis is a complex disease that is also affected by environmental factors such as genetic factors, diet, and lifestyle, especially in women, when menopause occurs, bone loss rapidly progresses due to hormonal changes.

There are vitamin D, female hormones, bisphosphonates, selective estrogen receptor modulators, and calcitonin preparations currently on the market for the treatment of osteoporosis. . However, because osteoporosis treatments through the suppression of osteoclast activity are basically not treatments for osteoporosis, there is a limit to cure and an increase in osteoblast activity that can actually increase bone density and strengthen bones is essential.

In addition, osteoporosis is a disease that cannot be treated only by short-term administration of a drug and long-term administration of the drug is essential, and thus there is a need to develop new substances having excellent medicinal properties without side effects even when the drug is administered for a long time.

Accordingly, in recent years, researches on alternative therapies using active ingredients derived from natural products such as herbal medicines and foods that can promote bone formation while minimizing side effects and bone loss of existing treatments have been actively conducted.

On the other hand, azelaic acid is a dicarboxylic aciid with two carboxyl groups (-COOH) in one molecule, found in wheat, rye and barley, as well as components of hair and skin conditioners. It is also a material used in various industrial products, including polymers and plasticizers.

Azelaic acid is already widely commercialized as an ointment for acne treatment, and as it is used as a main ingredient in cosmetics, studies related to skin treatment are mainly conducted. In Korean Patent No. 10-1326376, nanocapsules of azelaic acid and skim milk powder are used. There has been disclosed a method of manufacturing a cosmetic for acne treatment.

In addition, Korean Patent Registration No. 10-1593539 recently disclosed that azelaic acid can be used in the treatment of obesity because it shows an excellent effect in improving lipid accumulation and lipid metabolism in adipose tissue.

However, studies on the effect of azelaic acid on the proliferation and differentiation of osteoblasts have not been reported.

Korean Registered Patent No. 10-1326376 Korean Registered Patent No. 10-1593539

The present inventors tried to develop a new pharmaceutical composition that increases osteoblasts activity to substantially increase bone density and strengthen bone activity to treat osteoporosis, and has less side effects even when taken for a long time, while azelaic acid osteoblasts The present invention was completed by confirming that it promotes the proliferation and differentiation of.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition and a health functional food having excellent osteoporosis prevention and treatment efficacy and low side effects even when taken for a long time.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of osteoporosis containing the compound represented by the formula (1) as an active ingredient.

The pharmaceutical composition may be characterized by promoting osteoblast differentiation.

The compound represented by Chemical Formula 1 may be characterized by increasing the expression level of any one or more osteoblast differentiation marker genes among Runx2 (runt-related transcription factor 2), Dlx5 (distal-less homeobox 5) and OC (osteocalcin). Can be.

The concentration of the compound represented by Formula 1 may be characterized in that it is 0.0001 to 5 mM.

In addition, the present invention provides a health functional food for preventing or improving osteoporosis containing the compound represented by the following formula (1) as an active ingredient.

[Formula 1]

The pharmaceutical composition according to the present invention has the effect of promoting the differentiation of osteoblasts by increasing the expression level of the osteoblast differentiation marker genes Dlx5, Runx2, OC, and thus is widely used as a pharmaceutical or health food for the prevention or treatment of osteoporosis. Can be.

In addition, rather than targeting osteoclasts, by increasing the activity of osteoblasts, bone formation can be promoted to fundamentally treat osteoporosis, and there is an advantage of showing a secondary fracture prevention effect.

1 is a result of MTT experiment confirming the survival rate of cells according to the concentration of azelaic acid.
Figure 2 is a result of confirming the osteoblast differentiation gene expression in MC3T3-E1 cells cultured for 0, 1, 2, 4 days after treating azelaic acid at a concentration of 1 mM.
Figure 3 is a result of comparing osteoblast differentiation gene expression in MC3T3-E1 cells treated with azelaic acid, ascorbic acid, and beta-glycerophosphate mixtures, and MC3T3-E1 cells mixed with them.

Hereinafter, the present invention will be described in detail. Terms or words used in the present specification and claims should not be interpreted as being limited to a conventional or dictionary meaning, and the inventor may appropriately define the concept of terms to describe his or her invention in the best way. Based on the principle of being present, it should be interpreted as a concept of meaning ™™ consistent with the technical idea of the present invention.

The present invention relates to a pharmaceutical composition and a health functional food for the prevention or treatment of osteoporosis.

As used herein, the term osteoporosis refers to a condition in which the amount of bone is reduced and the strength of bone is weakened due to qualitative changes, and the prevention, improvement and treatment of osteoporosis includes all diseases caused by bone density reduction and bone loss. It is interpreted as.

The present invention provides a pharmaceutical composition for the prevention or treatment of osteoporosis containing the compound represented by the formula (1) as an active ingredient.

[Formula 1]

The compound represented by Chemical Formula 1 may be designated as azelaic acid or nonanedioic acid, and has a molecular formula of C ₉ H ₁₆ O ₄ and a molecular weight of 188.22 g / mol.

The compound represented by Formula 1 may be used in the form of a pharmaceutically acceptable salt, and an acid addition salt formed by a pharmaceutically acceptable free acid is useful as the salt. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes It is obtained from non-toxic organic acids such as dioate, aromatic acids, aliphatic and aromatic sulfonic acids, acetic acid, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid and the like. The types of pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and eye Odide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, sube Late, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, Glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate and the like.

The acid addition salt according to the present invention can be prepared by a conventional method, for example, a precipitate formed by dissolving a derivative of Formula 1 in an organic solvent such as methanol, ethanol, acetone, dichloromethane, acetonitrile, etc. and adding an organic acid or inorganic acid It can be prepared by filtration and drying, or by distilling the solvent and excess acid under reduced pressure and drying to crystallize under an organic solvent.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the inexpensive compound salt, and evaporating and drying the filtrate. At this time, it is suitable to manufacture sodium, potassium or calcium salts as metal salts. Further, the corresponding salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

Azelaic acid, which is a compound represented by Chemical Formula 1, may be one extracted from a natural product or a synthesized one by a known method, and the production method or origin is not limited.

Azelaic acid is known to be present in oxidized products of oxidized linseed oil, fungal spores, and keratin.It oxidizes ricinoleic acid to potassium permanganate and concentrated nitric acid, ozone decomposes oleic acid, or 9, 10-dihydrate It can be prepared by oxidizing hydroxystearic acid with dichromic acid and sulfuric acid.

The pharmaceutical composition may be characterized by promoting osteoblast differentiation.

Compounds that promote osteoblast differentiation can be used not only for the prevention or treatment of diseases and symptoms such as osteoporosis and fractures, but also for the treatment of periodontal disease for the purpose of strengthening bone (Zhang et al., ShanghaiKou Qiang Yi Xue 7 (2), pp99-103, 1998; Cahill et al, Biol Blood Marrow Transplant 10 (10), pp709-717, 2004), also reported that it may be useful in the treatment of burn-induced bone growth disorders. Bar (Klein et al., Osteoporos Int. 16 (6), pp631-635, 2005).

The pharmaceutical composition may be used without limitation to diseases having problems with bone formation due to lack of osteoblasts, and specifically bone destruction and inflammatory diseases caused by interleukin-1 (IL-1) due to lack of estrogen. Osteoporosis due to excessive bone resorption of osteoclasts, bone metastatic lesions, primary tumors in the bone, rheumatoid or degenerative arthritis, periodontal disease, inflammatory alveolar bone resorption disease, inflammatory bone resorption disease And pathological bone diseases such as Paget's disease, and the like, which may promote bone destruction.

The compound represented by Chemical Formula 1 may be characterized by increasing the expression level of any one or more osteoblast differentiation marker genes among Runx2 (runt-related transcription factor 2), Dlx5 (distal-less homeobox 5) and OC (osteocalcin). Can be.

Osteoblast differentiation includes hormones, cytokines such as Bone Morphogenetic Proteins (BMPs), Runx2 (runt-related transcription factor 2), Id1 (inhibitor of DNA binding 1), Dlx5 (distal-less homeobox 5), OC It is regulated by various transcription factors such as (osteocalcin) and ALP (alkaline phosphatase). Among them, Id1, Dlx5, and Runx2 are essential genes expressed early in osteoblast differentiation, and the expression of these genes means that osteoblast differentiation is accelerated.

Specifically, Runx2 (runt-related transcription factor 2) is widely known as an important regulator in osteoblast differentiation, and ALP (alkaline phosphatase), OC (osteocalcin), and bone sialoprotein (bone) in multipotent cells or osteoblast precursors sialoprotein) is a gene that promotes osteoblast differentiation by regulating genes.

Id1 (inhibitor of DNA binding 1) is a transcription factor that affects the balance between cell growth and differentiation in osteoblasts, and is known to play an important role in the early stages of osteoblast specific differentiation. In addition, differentiation is promoted by regulation of the expression of the inhibitor of DNA binding 1 (Id1) gene when the cells are converted from mesenchymal and mesenchymal stem cells to osteoblast differentiation.

Dlx5 (distal-less homeobox 5) is induced by bone and directly binds to a promoter of runx2 (runt-related transcription factor 2) to regulate transcription, and gene expression of osteocalcin (OC), a late marker for osteoblast differentiation Regulate osteoblast differentiation.

The concentration of the compound represented by Formula 1 may be characterized in that it is 0.0001 to 5 mM.

More specifically, the concentration of the compound represented by Formula 1 may be 0.0001 to 5 mM, preferably 0.0001 to 3 mM, and more preferably 0.0001 to 1 mM.

If, when the concentration of the compound represented by Formula 1 is less than the above-described range, the pharmaceutical effect may be insignificant, and if it exceeds the above-described range, there is a problem that cytotoxicity may appear.

The pharmaceutical composition may be administered orally or parenterally during clinical administration, and may be used in the form of a general pharmaceutical preparation.

The pharmaceutical composition may be characterized in that it is formulated in the form of powders, granules, tablets, hard capsules, soft capsules or injections.

More specifically, oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, sterile sterile injectable solutions, pre-filled injectable solutions, or lyophilized according to conventional methods, respectively. It may be formulated in a form, but is not limited thereto.

In the case of formulation, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc., which are commonly used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the active ingredient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be prepared by mixing. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients.

Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions, syrups, etc. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like.

The preferred dosage of the pharmaceutical composition of the present invention may be appropriately selected depending on the patient's condition and body weight, severity of symptoms, drug form, route and duration of administration.

In addition, the present invention provides a health functional food for preventing or improving osteoporosis containing the compound represented by the following formula (1) as an active ingredient.

[Formula 1]

The compound represented by Chemical Formula 1 may be designated as azelaic acid or nonanedioic acid, and has a molecular formula of C ₉ H ₁₆ O ₄ and a molecular weight of 188.22 g / mol.

The health functional food may be characterized by promoting osteoblast differentiation.

The compound represented by Chemical Formula 1 may be characterized by increasing the expression level of any one or more osteoblast differentiation marker genes among Runx2 (runt-related transcription factor 2), Dlx5 (distal-less homeobox 5) and OC (osteocalcin). Can be.

The concentration of the compound represented by Formula 1 may be characterized in that it is 0.0001 to 5 mM.

The concentration of the compound represented by Formula 1 may be 0.0001 to 5 mM, preferably 0.0001 to 3 mM, and more preferably 0.0001 to 1 mM.

If, when the concentration of the compound represented by Formula 1 is less than the above-described range, the pharmaceutical effect may be insignificant, and if it exceeds the above-described range, there is a problem that cytotoxicity may appear.

The health functional food may be manufactured in the form of, but not limited to, various beverages, gum, tea, sweets, vitamin complexes, health supplements, and the like.

In addition, the health functional food is also included in the case of being added to health food for the purpose of improving osteoporosis, there is no particular limitation on the type of food. Examples of foods to which the above substances can be added are meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other dairy products including noodles, gums, ice cream, various soups, beverages, teas, drinks, Alcoholic beverages and vitamin complexes, and all of the health foods in the ordinary sense.

The preferred intake amount of the dietary supplement varies depending on the intaker's condition and weight, the degree of symptoms, food type, and intake period, and may be appropriately selected.

In the process of bone formation, the differentiation of osteoblasts is regulated by the expression of genotypes and has unique characteristics depending on the culture method. Important signaling systems involved in bone cell differentiation and bone formation are typically transforming growth factor-β (TGF-β), bone morphogenetic protein (BMP), and wind / beta-catenin (Wnt / β-catenin), fibroblast growth factor (FGF), hedgehog, notch, and the like are known.

This signal transduction system induces expression and activation of various transcription factors related to bone formation, such as Runx2 (Runt-related transcription factor 2) and Dlx5 (Distalless-related homeobox 5) during bone cell differentiation, and ALP (alkaline phosphatase) , Id1 (inhibitor of DNA binding 1), OC (Osteocalcin) and expresses genes related to bone differentiation. As an inducer of differentiation in osteoblasts, ascorbic acid (AA), beta-glycerophosphate (β-GP), dexamethasone (dexamethasone), and the like are known.

In the present invention, experiments were conducted to investigate the effect of azelaic acid on the proliferation and differentiation of osteoblasts using MC3T3-E1 preosteoblasts, which are similar to osteoblasts present in bone tissue. It was confirmed that it showed a positive effect on cell proliferation and differentiation.

Hereinafter, the present invention will be described in detail, and examples and experimental examples will be described in detail. However, the embodiments according to the present invention can be modified in many different forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

<Experimental Example 1> MTT cytotoxicity experiment

(1) Cell culture

Cell line MC3T3-E1 (pre-osteoblast) is added with 1% penicillin-streptomycin (P / S, GIBGO) and 10% fetal bovine serum (FBS, ATLAS). (alpha-minimum essential medium, α-MEM, GIBGO).

In the experiments of the present invention MC3T3-E1 is a ^{2 × 10 4 cells / well,} 35% in the Petri dish ^{2 × 10 4 cells / well,} 3 × 10 4 cells / well in 24-well plates to 48-well plate (well plate) After dispensing, the cells were cultured in a 37 ° C, 5% CO ₂ incubator.

(2) MTT analysis

To evaluate the viability and toxicity of the cells, MTT analysis using absorbance was performed. Viable cells become yellow to purple by reducing 3- (4,5-dimethyl-thiazol-2-yl) -2,5-diphenyltetrazolium-bromide (MTT) to Formazan, and MTT The analysis is to determine the color change and measure the viability of the cells.

In this experiment, the MTT was treated with MC3T3-E1 cells, incubated for 1 hour in a CO ₂ incubator, and then treated with dimethyl sulfoxide (DMSO) after suction to confirm color change.

First, MC3T3-E1 was dispensed at 2 × 10 ⁴ cells / well in a 48 well plate, and the stock solution prepared with 1 mM by diluting azelaic acid with DMSO was 0, 0.0001, 0.001, 0.01, 0.1, Each well was treated at 1, 10 mM concentration.

Subsequently, after treating the MTT at a concentration of 100 uM, the cells were incubated for 1 hour at 37 ° C in a 5% CO ₂ incubator, and the reacted cells were dissolved in 400 μL of DMSO.

After dispensing 200 μL of the solution in each well into 96 wells, absorbance was measured at 540-570 mM using an Infinite M200PRO (Tecan) device.

(3) Experiment result

The MTT analysis results are shown in FIG. 1. As shown, it was confirmed that cells were killed when azelaic acid was treated at a concentration of 10 mM. Accordingly, in the experiments to be performed in the future, the experiment was conducted using 1 mM azelaic acid, which does not show toxicity.

<Experimental Example 2> Expression analysis of osteoblast differentiation marker according to azelaic acid treatment

(1) Experiment method

1) RNA extraction and cDNA synthesis

After treating azelaic acid at a concentration of 1 mM and culturing the media of each culture dish incubated for 0, 1, 2, 4 days, it was washed with 1 mL of Phosphate Buffer Salin (PBS). Thereafter, 300 μL of Trizol was lysed to lyse the cells, and each sample was recovered.

After each sample was reacted for 5 minutes at RT, 60 μL of chloroform was treated and reacted for 5 minutes at RT, and then added to a centrifuge (13,000 rpm, 4 ° C., 15 minutes).

After centrifugation, 150 μL of the supernatant was transferred to a new tube, and 150 μL of isopropyl alcohol was added and then inverted and stored at -20 ° C.

After centrifugation (13,000 rpm, 4 ° C, 15 min), the supernatant was removed, washed with 170 μL of ethanol (70%), and centrifuged again (13,000 rpm, 4 ° C, 15 min) to remove the supernatant. Dry for 5 minutes.

Finally, after dissolving pellets (RNA) in 20 μL of tertiary distilled water, RNA was quantified using an Infinite M200PRO (Tecan) device.

Subsequently, RNA samples quantified using TOPscript RT DryMIX (enzynomics), a cDNA synthesis kit, were added, and then reacted at 50 ° C. for 1 hour at 95 ° C. for 5 minutes at 95 ° C., and maintained at 4 ° C. to synthesize cDNA.

2) Real-time polymerase chain reaction (RT-PCR)

19 μL of a mixture of Forward, Revers primer, 2x kit (emerald) and distilled water (D.W) was added to 1 μL of cDNA, and the total volume was adjusted to 20 μL.

Genes that can confirm osteoblast differentiation, β-actin, Dlx5, Runx2, and OC primers (Sigma Aldrich Korea) were used, and the base sequences and experimental conditions of each primer are shown in Tables 1 and 2.

gene Primer Sequence Forward Reverse β-actin 5'-TTC TTT GCA GCT CCT TCG TTG CCG-3 ' 5'-TGG ATG GCT ACG TAC ATG GCT GGG-3 ' Runx2 5'-CCG CAC GAC AAC CGC ACC AT-3 ' 5'-CGC TCC GGC CCA CAA ATC TC-3 ' Dlx5 5'-CAG AAG AGT CCC AAG CAT CC-3 ' 5'-GAG CGC TTT GCC ATA AGA AG-3 ' OC 5'-GCA AAT AAG GTA GTG AAC AGA CTC C-3 ' 5'-GTT TGT AGG CGG TCT TCA AGC-3 '

gene Reaction conditions Cycle Number Pre-
Denaturation Denaturation Annealing Extention Post-
Extension hold β-actine 25 cycle 95 ℃ 5 minutes 95 ℃ 30 seconds 66 ℃ 30 seconds 72 ℃ 30 seconds 72 ℃ 5 minutes 4 ℃ Dlx5 30 cycle 95 ℃ 5 minutes 95 ℃ 30 seconds 63 ℃ 30 seconds 72 ℃ 30 seconds 72 ℃ 5 minutes 4 ℃ Runx2 30 cycle 95 ℃ 5 minutes 95 ℃ 30 seconds 62 ℃ 30 seconds 72 ℃ 30 seconds 72 ℃ 5 minutes 4 ℃ OC 30 cycle 95 ℃ 5 minutes 95 ℃ 30 seconds 60 ℃ 30 seconds 72 ℃ 30 seconds 72 ℃ 5 minutes 4 ℃

(2) Experiment result

1) Osteoblast differentiation gene expression according to the treatment time of azelaic acid

As a result of confirming gene expression through RT-PCR for each sample cultured for 0, 1, 2, 4 days at 1 mM concentration of azelaic acid, it was confirmed that osteoblast differentiation gene expression appears depending on the processing time of azelaic acid. Could (see Figure 2).

2) Osteoblast differentiation gene expression according to condition treatment

Ascorbic acid (AA) and beta-glycerophosphate (β-Glycerophosphate, β-GP) are used to induce osteoblast differentiation. The gene expression level of the treated and those mixed with each was compared.

At this time, after treating azelaic acid at a concentration of 1 mM, cells cultured for 4 days were used.

As a result of comparison, it was confirmed that the expression of the gene was increased when the mixture of all of them was mixed and treated than the mixture of ascorbic acid and beta-glycerophosphate and azelaic acid, respectively (see FIG. 3).

Meanwhile, the compound represented by Chemical Formula 1 according to the present invention may be formulated in various forms according to the purpose. The following are examples of some formulation methods in which the compound represented by Formula 1 according to the present invention is contained as an active ingredient, and the present invention is not limited thereto.

<Formulation Example>

1-1. Preparation of powder

500 mg of compound of formula 1

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight fabric to prepare a powder.

1-2. Preparation of tablets

500 mg of compound of formula 1

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2mg

After mixing the above components, tablets are prepared by tableting according to a conventional tablet manufacturing method.

1-3. Preparation of capsules

500 mg of compound of formula 1

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into a gelatin capsule to prepare a capsule.

1-4. Preparation of injection

500 mg of compound of formula 1

Suitable amount of sterile distilled water for injection

pH Adjuster

It is prepared with the above-mentioned ingredient content per ampoule (2 ml) according to the preparation method of a conventional injection.

1-5. Preparation of liquid

100 mg of compound of formula 1

Isomerized sugar 10 g

5 g mannitol

Purified water

Each component was added to the purified water to dissolve it according to the preparation method of a conventional liquid formulation, lemon scent was added in an appropriate amount, and then the above components were mixed, and then purified water was added to adjust the total to 100 ml, followed by filling into a brown bottle. Liquid is prepared by sterilization.

Claims (5)

A pharmaceutical composition for the prevention or treatment of osteoporosis containing the compound represented by the following formula (1) as an active ingredient.
[Formula 1]

According to claim 1,
The pharmaceutical composition is a pharmaceutical composition for the prevention or treatment of osteoporosis, characterized in that to promote osteoblast differentiation.
According to claim 1,
The compound represented by Formula 1 is characterized by increasing the expression level of any one or more osteoblast differentiation marker genes among Runx2 (runt-related transcription factor 2), Dlx5 (distal-less homeobox 5) and OC (osteocalcin) Pharmaceutical composition for the prevention or treatment of osteoporosis.
According to claim 1,
The pharmaceutical composition for preventing or treating osteoporosis, characterized in that the concentration of the compound represented by Formula 1 is 0.0001 to 5 mM.
A health functional food for preventing or improving osteoporosis containing the compound represented by the following formula (1) as an active ingredient.
[Formula 1]

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