KR20130113150A - Pharmaceutical composition and functional health food for prevention or treatment of diseases relating to bone mass loss including hs1792 or its pharmaceutically acceptable salts - Google Patents

Abstract

PURPOSE: A pharmaceutical composition and a health food containing HS1792 for preventing diseases related to bone mass loss are provided to suppress bone absorption and to reduce the expression of a gene related to osteoclast differentiation, thereby effectively preventing and treating osteoporosis. CONSTITUTION: A pharmaceutical composition for preventing or treating diseases related to bone mass loss contains a compound of chemical formula 1 or a pharmaceutically acceptable salt thereof. The pharmaceutical composition suppresses the expression of one or more selected among tartrate-resistant acid phosphatase (TRAP), a calcitonin receptor, and cathepsin K. The diseases related to bone mass loss are selected among age-related primary osteoporosis, menopause-related primary osteoporosis, and postoophorectomy osteoporosis. A health food for suppressing osteoporosis contains the compound of chemical formula 1.

Description

TECHNICAL FIELD The present invention relates to a pharmaceutical composition and a health functional food for preventing or treating bone loss-lowering diseases, including HS1792 or a pharmaceutically acceptable salt thereof, acceptable salts}

The present invention relates to a pharmaceutical composition for preventing or treating diseases associated with lowering of bone mass and a health functional food having osteoporosis-inhibiting ability.

The bone is repeatedly cycled from about 120 to 150 days, including osteoclast-induced bone resorption, osteoblast-induced osteogenesis and dormancy (called remodeling). In healthy adults, bone resorption and bone formation are strictly controlled, and the total bone mass remains almost unchanged. However, in diseases associated with lowering of bone mass, the balance between the two falls, resulting in lowering of bone mass and deterioration of bone tissue. The decrease in bone mass is 20 to 30%, which makes it easier to fracture, which can lead to sickness, deformity, or death depending on the fracture site such as hip fracture.

Osteoporosis is a typical bone disease-related disease. Osteoporosis is a systemic disease that is characterized by decreased bone mass and deterioration of bone tissue.

Osteoporosis is a condition in which the lime of the bony tissue is reduced and the density of the bone becomes thinner, thereby expanding the bone marrow cavity. As the condition progresses, the bones become weak, so that even a small impact is liable to fracture. The bone mass is affected by various factors such as genetic factors, nutritional intake, hormonal changes, exercise and lifestyle differences, and the causes of osteoporosis include age, lack of exercise, low birth weight, smoking, low calcium diet, Ovariectomy and the like are known. However, there are individual differences, but blacks have lower bone resorption levels than blacks, and bone mass is higher. In general, bone mass is highest at 14-18 years old and decreases about 1% per year at old age. Especially in women, bone reduction continues after 30 years of age, and bone turnover is rapidly progressed by hormonal changes in menopause.

Although osteoporosis is different in the degree of osteoporosis, it is an unavoidable symptom for the elderly, especially postmenopausal women. In developed countries, as the population ages, interest in osteoporosis and its therapeutic agent is gradually increasing. In addition, it is known that there is a market of about $ 130 billion related to the treatment of bone diseases around the world, and since it is expected to increase further in the future, each research institute and pharmaceutical company in the world invests heavily in the development of bone disease treatments .

Bones remain healthy through bone remodeling that replaces damaged or old bone with new bone. The bone reshaping process is performed by osteoblasts and osteoclasts. Osteoblasts are involved in bone formation that creates new bone, and osteoclasts are involved in bone resorption that destroys old bone. However, when female hormone deficiency is manifested by menopause, it directly or indirectly affects osteoblasts and osteoclasts involved in the remodeling process of bone, resulting in bone loss. That is, reshaping of post-menopausal bone becomes active and the degree of bone resorption becomes higher than the degree of bone formation, resulting in bone loss.

Treatment of osteoporosis includes general and drug therapy. Common therapies require intake of calcium and vitamin D, changes in exercise and lifestyle, and hormone replacement therapy, alendronate, calcitonin, latoxifene, Na-F, calcitriol, and bisphosphonate. The treatment of osteoporosis requires a long term treatment period and it is necessary to develop a new therapeutic agent for osteoporosis which has side effects such as urinary stone, endometrial cancer and breast cancer when the conventional drug is taken for a long time and has no adverse effect on the human body.

Currently, substances used for the treatment of osteoporosis include estrogen, androgenic anabolic steroids, calcium preparations, phosphates, fluoride preparations, ipriflavone, and vitamin D3. In 1995, Merck Inc., USA, developed aminobisphosphonate, and in 1997, Rilley, USA, developed raloxifene, a selective estrogen receptor modulator, as a new drug for osteoporosis.

On the other hand, conventional osteoporosis medicines are mostly estrogenic substances, and estrogenic substances are known to exhibit side effects such as cancer, gallstones, and thrombosis when they are administered for a long period of time. However, since osteoporosis can not be treated only by short-term administration of the drug and long-term administration of the drug is essential, there is no such side effect when the drug is administered for a long period of time, and development of a new substance having a drug efficacy sufficient to replace estrogen is urgently required It is a situation.

Korean Patent Publication No. 1997-0705397 (published on October 10, 1997) discloses estrogen compounds and parathyroid hormone for the treatment of osteoporosis.

Korean Patent Publication No. 1997-0705397

The present invention aims to provide a pharmaceutical composition for preventing or treating bone loss-lowering-related diseases and a health functional food having osteoporosis-inhibiting ability.

1. A pharmaceutical composition for preventing or treating bone loss-lowering diseases comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:

[Formula 1]

2. The pharmaceutical composition according to 1 above, wherein said pharmaceutical composition inhibits the expression of at least one selected from the group consisting of tartrate-resistant acid phosphatase (TRAP), calcitonin receptor and cathepsin K, ≪ / RTI >

3. The pharmaceutical composition according to 1 or 2 above, wherein the disease associated with lowering of bone mass is at least one selected from the group consisting of primary osteoporosis due to aging, primary osteoporosis due to menopause, and primary osteoporosis due to oophorectomy.

4. The method according to claim 1 or 2, wherein the disease associated with lowering of bone mass is selected from the group consisting of glucocorticoid-induced osteoporosis, thyroid glandular osteoporosis, immobilization-induced osteoporosis, heparin-induced osteoporosis, immunosuppressive osteoporosis, osteoporosis due to renal failure, Osteoporosis according to Cushing's syndrome and rheumatoid osteoporosis.

5. The pharmaceutical composition according to 1 or 2, wherein the disease associated with lowering of bone mass is at least one selected from the group consisting of cancer bone cancer, hypercalcemia, vesicle disease, bone defect and osteonecrosis.

6. A health functional food having osteoporosis-inhibiting ability comprising a compound represented by the following formula 1:

[Formula 1]

.

.

7. In section 6 above, the following items are to be considered: dairy, confectionery, seasonings, beverages and drinks, snacks, candies, ice cream and frozen desserts, breakfast cereals, nutrition bars, snack bars, chocolate products, processed foods, And dressings, confectionery products, oil and fat products, dairy drinks and milk drinks, soy dairy-like products, frozen foods, cooked foods and alternative foods, meat products, cheese, yogurt, bread And at least one selected from the group consisting of buns, yeast products, cakes, cookies, and crackers.

8. The health functional food according to 6 above, wherein the formulation is selected from the group consisting of capsules, tablets, powders, liquid suspensions, pills and granules.

The HS1792 of the present invention inhibits bone resorption and reduces the expression of osteoclast target gene-related mRNA by about 2 to 5 times to inhibit osteoclast differentiation and does not show any toxic signal.

In addition, the histological findings of the skull showed that the degree of bone damage was markedly reduced as compared with the bone resorption model, and thus it was confirmed that the composition containing the same was effective for preventing or treating the bone loss-lowering-related diseases of the present invention. It can be useful as medicines and foods effective for treatment.

FIG. 1 is a microphotograph showing the number of differentiated osteoclasts after culturing for 9 days by treatment with HS1792 in combination with osteoclast differentiation agents (M-CSF and RANKL) to macrophages obtained from mouse bone marrow by TRAP staining.
FIG. 2 is a graph showing the degree of differentiation into differentiated osteoclasts after culturing for 9 days with HS1792 treated with osteoclast differentiation agents (M-CSF and RANKL) in macrophages obtained from mouse bone marrow. A is the number of osteoclasts and B is a graph quantified by measuring TRAP activity.
FIG. 3 is a graph showing the results of bone morphogenesis after culturing in a hydroxyapatite-coated well plate for 9 days by treating HS 1792 with osteoclast differentiation agent (M-CSF and RANKL) It is the result of confirming the area. A is a microscope photograph, B is a pit area, and C is a graph showing the number of pits absorbed.
FIG. 4 is a graph showing the expression of osteoclast target gene-related mRNA expression in cells obtained after 9 days of HS 1792 treatment with osteoclast differentiation agents (M-CSF and RANKL) in macrophages obtained from mouse bone marrow . A is TRAP, B is calcitonin receptor, and C is cathepsin K-related mRNA expression.
FIG. 5 is a micro-computed tomography scan of a skull obtained after daily injections of HS1792 at 10 mg / kg for 6 days in an animal model of LPS-induced bone resorption and reconstructed in three dimensions.
FIG. 6 is a photograph (A) showing a cross section of a skull obtained by injecting HS1792 at 10 mg / kg daily for 6 days in an LPS-induced bone resorption animal model and a graph (B) quantifying the area of the osteoclast- to be.
FIG. 7 is a graph showing the bone analysis of the femur obtained after injecting HS1792 at a dose of 10 mg / kg into the abdominal cavity 24 times at 2-day intervals in an ovariectomized animal model. A is the holding bone mass, B is the holding bone thickness, C is the holding bone marrow, and D is the holding space area.

The present invention relates to a pharmaceutical composition for preventing or treating bone loss-lowering diseases comprising HS1792 or a pharmaceutically acceptable salt thereof, and a health functional food having osteoporosis-inhibiting ability, and more particularly, Related osteoclast differentiation-related genes, thereby inhibiting the development of osteoporosis. The present invention also relates to a pharmaceutical composition for preventing or treating osteoporosis-related diseases and a health functional food having osteoporosis-inhibiting ability.

Hereinafter, the present invention will be described in more detail.

In the present invention "HS1792" is a molecular formula is C ₁₆ H ₁₂ O ₂ to 6- (3-hydroxyphenyl) resveratrol derivative having the formula 2-naphthol, molecular weight is 236.0837.

The chemical structure of this material is shown in Formula (1). "Resveratrol" is a natural substance found in herbs, grape skin, nuts and red wine.

The HS1792 of the present invention inhibits the expression of at least one selected from the group consisting of tartrate-resistant acid phosphatase (TRAP), calcitonin receptor and cathepsin K, inhibits osteoclast formation or proliferation, reduces osteoclast numbers , Effectively alleviating the disease in various osteoporosis animal models.

[Formula 1]

The disease associated with lowering of bone mass as referred to in the present invention refers to a disease in which a decrease in bone mass accompanies symptoms such as lowering of bone density and deterioration of bone tissue. Examples of diseases associated with lowering of bone mass include,

1) primary osteoporosis (e.g., primary osteoporosis due to aging, primary osteoporosis due to menopause, primary osteoporosis due to oophorectomy)

2) secondary osteoporosis such as glucocorticoid-induced osteoporosis, thyroid glandular osteoporosis, fixed-induced osteoporosis, heparin-induced osteoporosis, immunosuppressive osteoporosis, osteoporosis due to renal failure, inflammatory osteoporosis, osteoporosis due to Cushing's syndrome, Rheumatoid osteoporosis, etc.),

3) bone diseases such as cancer bone cancer, hypercalcemia, vesicle disease, bone defects (alveolar bone defect, mandible defect, childhood abnormal bone defect, etc.), osteonecrosis and the like.

Pharmaceutically acceptable salts of 6- (3-hydroxyphenyl) -2-naphthol (HS1792) represented by the formula (1) include salts of acidic or basic groups which may be present in the compounds of formula (1) do. For example, pharmaceutically acceptable salts include the sodium, calcium, and potassium salts of the hydroxy groups and can be prepared through the preparation or manufacturing processes of salts known in the art.

The 6- (3-hydroxyphenyl) -2-naphthol may be contained in the total pharmaceutical composition in an amount of 0.001 to 50% by weight, preferably 0.01 to 20% by weight. In addition, the 6- (3-hydroxyphenyl) -2-naphthol may be adjusted so that an appropriate amount per kg of the individual to which the pharmaceutical composition is administered in the whole pharmaceutical composition can be administered. For example, when the subject to be administered is a rat, the 6- (3-hydroxyphenyl) -2-naphthol has a content of 50 mg / kg to 150 mg / kg, preferably 80 mg / kg to 120 mg / kg The amount contained in the pharmaceutical composition can be adjusted. When the subject to be administered is a human, the 6- (3-hydroxyphenyl) -2-naphthol is used in an amount of 0.0001 to 500 mg / kg, preferably 0.001 to 500 mg / kg, more preferably 0.001 to 300 mg / kg The content contained in the pharmaceutical composition can be adjusted so that it can be administered in a dose amount.

The pharmaceutical composition of the present invention does not increase the drug efficacy, but may further contain ingredients that are commonly used in pharmaceutical compositions and can improve odor, taste, and visual appearance. The composition may further comprise inorganic or organic additives such as vitamins B1, B2, B6, C, E, niacin, carnitine, betaine, folic acid pantothenic acid, biotin, zinc, iron, calcium, chromium, magnesium, As shown in FIG. In addition, the composition may be used alone or may contain a substance having a prophylactic or therapeutic activity against previously used bone loss-related diseases.

The pharmaceutical compositions of the present invention comprise a pharmaceutically acceptable carrier and may be formulated for oral or parenteral administration for human or veterinary use. When the composition of the present invention is formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants can be used. Solid form preparations for oral administration include tablets, pills, powders, granules and capsules, which may contain at least one excipient such as starch, calcium carbonate ), Sucrose or lactose, and gelatin. In addition to simple excipients, lubricants such as magnesium, styrene, and talc may be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions and syrups, and various excipients such as wetting agents, sweetening agents, fragrances and preservatives in addition to commonly used simple diluents such as water and liquid paraffin . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of non-aqueous solvents and suspensions include vegetable oils such as propylene glycol, polyethylene glycol and olive oil, injectable esters such as ethyl oleate, and the like.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term " pharmaceutically effective amount " as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dosage level will vary depending on the sex, age, The activity of the compound, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. May be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art. The method of administering the composition comprising the compound produced by the production method of the present invention is preferably oral administration or intravenous administration. The dosage level for a particular patient may vary depending on the sex, age, health condition, diet, time of administration, method of administration, drug mix and severity of the disease.

The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the inhibition of diseases associated with lowering of bone mass.

In another embodiment of the present invention, the present invention may relate to a health functional food having osteoporosis-inhibiting ability, including HS1792.

There is no particular limitation on the kind of the health functional food. Examples include dairy products, confectionery, seasonings, beverages and drinks, snacks, candies, ice cream and frozen desserts, breakfast cereals, nutrition bars, snack bars, chocolate products, processed foods, cereal products and pasta, soups, sauces and dressings, Dairy products and dairy products, dairy drinks and milk drinks, soy dairy-like products, frozen foods, cooked foods and alternative foods, meat products, cheese, yogurt, bread and buns, yeast products , A cake, a cookie, and a cracker, but is not limited thereto, and includes all health foods in a conventional sense.

The health functional food of the present invention may be formulated into capsules, tablets, powders, liquid suspensions, pills and granules, but is not limited thereto.

The health functional food in the form of tablets can be prepared as it is, or it can be prepared by putting an excipient, binder, disintegrant or other additives into the granules in an appropriate manner and then compressing them by putting in a lubricant or the like, It may be prepared by direct compression molding of an even mixture of excipients, binders, disintegrants, or other suitable additives, or by mixing the preformed granules with the appropriate health food or by adding appropriate additives, followed by compression molding, A binder or another suitable additive is added to wet the powder evenly mixed with a solvent, the wet powder is molded into a mold at a low pressure, and dried by a suitable method. In addition, a mating agent or the like may be added to the health functional food in the form of tablets, if necessary.

Hard capsules in capsular health functional foods are prepared by uniformly mixing capsules with an excipient suitable for a health functional food or a health functional food, or by granulating the mixture into a granular form by a suitable method or by granulating it into a granular form suitable for a granular form, The soft capsules are usually capsules filled with a suitable functional food or an excipient suitable for a health functional food, and then encapsulated with a capsular base agent having increased firing by adding glycerin or sorbitol to a suitable capsule base such as gelatin, , And if necessary, a coloring agent preservative or the like may be added to the capsule base.

The health functional food of the ring form is usually prepared by mixing an excipient, a binder and a disintegrant in an ordinary healthy functional food, shaping it into a spherical form by an appropriate method, and then adding a gelatin to starch or other suitable skin agent, It may also be an objectionable substance.

The health functional food of the granular formulation is usually prepared by mixing the health functional food as it is or the excipient, binder, disintegrant etc. into the health functional food, and then making it into a granular form by a proper method and evenly grinding the particles as much as possible. , A mating agent, and the like.

The health functional food of the beverage formulation may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates are sugar saccharides such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. Functional materials such as folic acid extracts, fructooligosaccharides that help defecation and absorption of calcium, acacia honey, complex gold extract as a natural preservative, and gellan gum as a precipitation improving agent may be added, but not limited thereto, Suitable components may be suitably used. The ratio of the natural carbohydrate is generally about 0.001 to 0.4 g, preferably about 0.002 to 0.03 g per 100 ml of the food composition of the present invention.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. It will be apparent to those skilled in the art that various modifications and variations are possible within the scope and spirit of the present invention, and such variations and modifications are obvious to those of skill in the art .

Manufacturing example . For intraperitoneal administration of mouse HS1792  Injection preparation

The injectable solution for the treatment of diseases associated with lowering of bone mass according to the present invention is prepared by weighing HS1792 as necessary by using an electronic balance, dissolving in DMSO, and diluting in sterilized PBS to 10% DMSO. The injections were injected at a dose of 10 mg / kg once daily for 6 days in a total of 6 injections on the head of the lid of the LPS-induced bone destruction animal model, and once per 2 days in the abdominal cavity of the ovariectomized animal model at 10 mg / kg Twenty-four injections were performed at intervals of 8 weeks.

Example  One. HS1792 Of osteoclast formation or proliferation inhibition

1) Bone marrow cell culture and osteoclast differentiation

Bone marrow cells were prepared by removing muscle tissue around the legs (femur, shin bone) of 6-8 week old Balb / c mice, transferring them to a clean bench, cutting both ends of the femur, inserting a needle, And then washed with the medium. The bone marrows were collected and centrifuged at 2000 rpm for 5 minutes to obtain cells. The cells were resuspended in α-MEM medium containing 10% FBS, and the cells were dispensed into a culture dish and cultured at 37 ° C. in a wet condition with 5% CO 2 ₂ incubator. After 24 hours, the unattached cells were harvested and centrifuged at 2000 rpm for 5 minutes to collect the cells. The cells were cultured in an alpha-M medium containing M-CSF (50 ng / ml) and 10% FBS for 3 days, ≪ / RTI > After 3 days, adherent cells were collected and cultured in α-M medium containing M-CSF (50 ng / ml), RANKL (50 ng / ml) and 10% FBS to induce osteoclast differentiation.

2) Confirm the effect on osteoclast formation

The macrophages obtained by the above culture method were inoculated into a 48-well plate, and HS1792 was added to the wells for each concentration and cultured for 9 days. Cells were stained with 10% formaldehyde and stained with tacrolate - resistant acid phosphatase (TRAP), a cytochemical labeling enzyme capable of identifying osteoclasts. The number of osteoclasts was determined by counting the number of multicellular cells expressing TRAP (see Fig. 1). A commercially available kit (Sigma, USA) was used for the staining, and TRAP-positive cells and TRAP activity were measured in the same nucleus as above (see FIG. 2).

Experimental results As shown in Fig. 1 and Fig. 2, it was confirmed that osteoclast formation was reduced in a concentration-dependent manner by treatment with HS1792.

3) In bone resorption (pit formation)  Identify the impact

The macrophages obtained by the above culture method were inoculated on a well plate (Biologic, BD) coated with hydroxyapatite (hydroxyapatite), and HS1792 was added to the wells for each concentration and cultured for 9 days. The pit area formed on the hydroxyapatite slide was measured and compared with the control group.

As a result of the experiment, it was confirmed that the resorbed area differs by about 3 times and the number of pits is about 10 times that of HS1792 (see FIG. 3).

4) osteoclast target gene related mRNA Decreased expression of

RNA was extracted from the cells obtained by the above culture method to observe the expression of osteoclast target gene-related mRNA which expresses TRAP, calcitonin receptor and cathepsin K, by reverse transcriptase PCR.

As a result, the expression of TRAP mRNA was about 4 to 5 times, the expression of calcitonin receptor mRNA was about 2 to 3 times, and the expression of cathepsin K-related mRNA was suppressed about 5 times. Thus, expression of osteoclast differentiation- (See FIG. 4).

Example  2. LPS -Judo Bone resorption  Experiment on osteoporosis treatment using mouse model

For the LPS-induced bone resorption animal model, C57BL / 6 female 20-25g mice were purchased from Hyochang Science Co. and used for the experiment. The experiment was carried out at the Animal Husbandry Department, College of Pharmacy, Pusan National University, where the temperature was set at 18 ~ 22 ℃, 40 ~ 60% relative humidity and 12 hours of illumination time (day and night cycle).

The LPS-induced bone resorption mouse model is an osteoporosis model with similar characteristics of human osteoporosis and was prepared as follows.

LPS (lipopolysaccharide) was dissolved in PBS and injected into mice at two doses at 12.5 mg / kg to prepare a bone resorption mouse model. HS1792 was dissolved in PBS at 10 mg / kg and injected into mice twice a day for 6 days in total for 6 times. On the other hand, in the vehicle-treated group, only PBS was injected into the two mice. After 6 injections, the mouse skull was extracted and 3-dimensionally analyzed. The extracted skull was photographed with a micro-computed tomography scan device and reconstructed with a software program.

Experimental results showed typical osteoporosis findings in which bone loss was observed in the skull of a vehicle-injected mouse, HS1792-treated mice showed similar findings to normal mice, and the therapeutic effect of osteoporosis was visually confirmed (see FIG. 5) .

Each mouse skull was separated and fixed in 10% neutral buffered formalin (NBF) fixative, decalcified with 10% EDTA solution, and embedded in paraffin. Then, a tissue slice of 4 μm was prepared and TRAP staining was performed.

As a result, the HS1792-treated group showed a bone area of about 2 to 3 times that of the LPS-treated control group, indicating that bone resorption was suppressed (see FIG. 6). HS1792 also showed no toxicity and no mortality.

Example  3. Experimental and bone analysis of osteoporosis treatment using ovariectomized animal model

For ovariectomized animal model, 20-25g female C57BL / 6 female mice were purchased from the Central Laboratory Animals, and only healthy animals that showed adaptability after quarantine and purification for 2 weeks were used in the experiment. This experiment was carried out with a specific pathogen free (SPF) animal with an incubation environment set at 18-22 ° C, 40-60% relative humidity and 12 hours of illumination time (day and night cycle) It was carried out in the breeding room. All mice were fed ad libitum animal feed and sterile water (negative water) ad libitum.

An ovariectomized animal model is an osteoporosis model having similar characteristics to osteoporosis in humans and was prepared as follows.

For the ovariectomized model, the sham model, a normal control group, was purchased from the central experimental animal.

Bilateral ovariectomies were performed in PBS - treated group and HS1792 - treated group, except Sham group. The anesthetized mouse was removed from the abdomen of the lower abdomen, the surgical site was disinfected, and surgery was performed under sterile conditions. The skin, abdomen, and peritoneum were dissected and the ovaries were exposed with disinfected tweezers to ligate the fallopian tubes to the silk, and the left and right ovaries were removed. Antibiotics were injected into the peritoneal cavity to prevent infection, and peritoneal, abdominal, and skin were sealed with absorbable sutures.

The experimental procedures were as follows: ovariectomy, recovery procedure after extraction, sham mouse after HS1792 (10 mg / kg) 24 times peritoneal cavity, ovariectomized osteoporosis-induced mouse and osteoporotic osteoporosis induced HS1792- The analysis of bone (the amount of stratum bone, the thickness of stratum bone, the number of stratum margins, and the space of stratum space) was performed (see FIG. 7).

In the experimental group treated with HS1792, approximately 20% to 60% of all four indicators of the postural bone mass, the posterior bone thickness, the posterior bone marrow, and the footprint area were effective, and the effect of the HS1792- I could.

As a result of the above test, HS1792-treated group had decreased bone resorption and osteoclast number compared to osteoporosis mice. In addition, the histological findings of the skull showed that the degree of bone damage was significantly reduced as compared with the bone resorption model, and thus it was confirmed that the present invention is effective in suppressing or preventing the development of diseases associated with bone loss.

Claims (8)

A pharmaceutical composition for preventing or treating a disease related to bone loss, including a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof:
[Formula 1]

The method of claim 1, wherein the pharmaceutical composition is a pharmaceutical for preventing or treating bone loss-related diseases that inhibit the expression of one or more selected from the group consisting of tartrate-resistant acid phosphatase (TRAP), calcitonin receptor and cathepsin K Composition.
The pharmaceutical composition according to claim 1 or 2, wherein the disease related to bone loss is at least one selected from the group consisting of primary osteoporosis with age, primary osteoporosis with menopause, and primary osteoporosis with ovarian extraction.
The method according to claim 1 or 2, wherein the disease associated with bone loss is glucocorticoid-induced osteoporosis, hyperthyroidism osteoporosis, fixed-induced osteoporosis, heparin-induced osteoporosis, immunosuppressive osteoporosis, osteoporosis following renal failure, inflammatory osteoporosis, Cushing syndrome Pharmaceutical composition according to at least one selected from the group consisting of osteoporosis and rheumatoid osteoporosis.
The pharmaceutical composition according to claim 1 or 2, wherein the disease related to bone loss is at least one member selected from the group consisting of cancer metastasis, hypercalcemia, Bejet's disease, bone defect and bone necrosis.
A health functional food having osteoporosis-inhibiting ability comprising a compound of the following formula:
[Formula 1]

7. The method of claim 6, further comprising the steps of: preparing the dairy product, the confectionery, the seasoning, the beverage and the drink, the snack, the candy, the ice cream and the frozen dessert, the morning cereal, the nutrition bar, , Confectionery products, oil and fat products, dairy drink and milk beverage, soy dairy-like product, frozen food, cooked food and substitute food, meat products, cheese, yogurt, bread and bun , Yeast products, cakes, cookies, and crackers.
7. The health functional food according to claim 6, wherein the formulation is selected from the group consisting of capsules, tablets, powders, liquid suspensions, pills and granules.

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