KR101438255B1 - Composition comprising the curcumin for bone growth-promoting effects - Google Patents

Abstract

The present invention relates to a novel use of curcumin, and more particularly, to a composition for promoting bone growth comprising curcumin as an active ingredient. Curcumin according to the present invention inhibits bone resorption, increases bone formation as well as restores bone loss when administered to an animal model in which bone loss is induced, The composition of the present invention including curcumin is useful as a preventive and therapeutic agent for bone diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, degenerative arthritis, disc, osteogenesis, Paget's disease, rickets and fibrous dysplasia, There is an effect that the composition can be used as a pharmaceutical composition and a functional food composition for the purpose of treatment or improvement.

Description

[0001] The present invention relates to a composition for promoting bone growth comprising curcumin as an active ingredient,

The present invention relates to a composition containing curcumin as an active ingredient and having a bone growth promoting effect. More specifically, the present invention relates to a composition for promoting bone growth containing curcumin having an activity of inhibiting bone loss and promoting bone formation ≪ / RTI >

Bone tissue is a specially differentiated type of connective tissue that plays a supporting role in higher vertebrates and is a tissue that undergoes lifelong remodeling. During the growing phase, the amount of bone formation gradually increased and the bone mass reached its maximum value in the early 30s. Thereafter, the formation and loss of bone were balanced to a similar degree, so that the overall bone mass remained constant. And the bone mass is decreased.

Bone remodeling occurs over a period of time and occurs locally at narrow sites, which maintains the structure of the skeletal system. The structure and function of the skeletal system is regulated by the complex interactions between systemic hormones and local factors.

Bone tissue is a connective tissue composed of various kinds of cells such as mesenchymal cells, cartilage cells, osteoblasts, osteoclasts, macrophages, mononuclear cells, endothelial cells and bone marrow cells, all of which are not only circulating endocrine materials, It is known to respond to growth regulators.

However, when the metabolic process of the bone regeneration is lost by the regulatory factors, various bone diseases may occur. When excessive bone resorption occurs, osteoporosis, Paget disease and rheumatoid arthritis occur in the bone tissue.

Osteoporosis is especially frequent in postmenopausal women, which is a disease in which bone mass is markedly decreased by the decrease of estrogen secretion. The decrease in bone mass is due to individual differences or various other causes, but if the bone mass is reduced excessively to a certain value, the fracture easily occurs even in case of mild impact.

Therefore, in addition to endogenous regulators, various substances have been studied for the purpose of treating or preventing osteoporosis caused by excessive osteoclast activity. Drugs currently used for this purpose exhibit a certain pharmacological action but are known to have various side effects and difficulties in taking the drug. Therefore, there is a desperate need for the development of a new therapeutic agent having excellent toxicity and side effects and excellent prevention or treatment of osteoporosis In particular, efforts are being actively made to discover new therapeutic agents from natural sources to reduce side effects.

Also, in the case of active inhibition substance of osteoclast. However, it is necessary to develop an anabolic reagent that promotes bone formation in order to maintain desirable bone density when bone loss progresses considerably.

However, the effect of curcumin, which is extracted from natural ingredients, to prevent or treat bone diseases by promoting bone growth is not yet known.

Accordingly, the inventors of the present invention first confirmed that curcumin has an effect of promoting bone growth, confirming that curcumin can be used as a composition for promoting bone growth, and completed the present invention.

Accordingly, an object of the present invention is to provide a composition for promoting bone growth containing curcumin as an active ingredient.

Another object of the present invention is to provide a composition for preventing or treating bone diseases containing curcumin as an active ingredient.

It is still another object of the present invention to provide a health food for preventing or ameliorating bone diseases containing curcumin as an active ingredient.

In order to achieve the object of the present invention, the present invention provides a composition for promoting bone growth comprising curcumin as an active ingredient.

In one embodiment of the present invention, the curcumin may be obtained by adding water or an organic solvent to turmeric.

In one embodiment of the present invention, the organic solvent may be a lower alcohol having 1 to 4 carbon atoms.

In one embodiment of the present invention, the curcum may have an effect of promoting growth of bone length, promoting bone strengthening, suppressing bone resorption, promoting differentiation and proliferation of osteoblast, or increasing bone mass

The present invention also provides a composition for preventing or treating bone diseases containing curcumin as an active ingredient.

In one embodiment of the present invention, the bone disease may be selected from the group consisting of osteoporosis, rheumatoid arthritis, osteoarthritis, degenerative arthritis, disc, osteomalacia, Paget's disease, rickets and fibrous dysplasia.

The present invention also provides a health food for preventing or ameliorating bone diseases containing curcumin as an active ingredient.

In one embodiment of the present invention, the bone disease may be selected from the group consisting of osteoporosis, rheumatoid arthritis, osteoarthritis, degenerative arthritis, disc, osteomalacia, Paget's disease, rickets and fibrous dysplasia.

Curcumin according to the present invention has an effect of inhibiting bone resorption, increasing bone formation as well as restoring bone loss, and has an effect of increasing bone mass. Therefore, Curcumin The composition of the present invention includes a pharmaceutical composition and a functional food composition capable of preventing, treating or improving osteoporosis, rheumatoid arthritis, osteoarthritis, degenerative arthritis, disc, osteoarthritis, Paget's disease, rickets and fibrous dysplasia There is an effect that can be used.

FIG. 1 is a graph showing an X-ray photograph of a curcumin-treated group and a control group in an animal model. FIG.
FIG. 2 is a graph showing the relative bone density and relative bone length of the femur metaphysis of the curcumin-treated group and the control group in an ovariectomized animal model.
FIG. 3 is a graph showing the relative bone densities and relative bone lengths of the femoral epiphysis and metaphysis of the curcumin-treated group and the control group in an animal model.
FIG. 4 is a graph showing the relative activity of ALP by curcumin when bone marrow stromal cells were cultured under bone differentiation conditions. FIG.

The present invention is characterized by providing a composition for promoting bone growth containing curcumin as an active ingredient.

Curcumin, an active ingredient of the composition for promoting bone growth according to the present invention, is usually contained in a large amount of turmeric (or corn) and is well known as a causative component in turmeric.

In addition, curcumin, the main component of turmeric, is widely used in the treatment and prevention of active oxygen, pain relief and relief, prevention of hemorrhagic and skin diseases, prevention of dementia and aging, treatment of fever, improvement of detoxification enzyme activity, prevention of diabetes, hypertension and arteriosclerosis, , Anti-inflammation, hemorrhoids, hangovers, diabetes prevention and improvement. However, the use of such curcumin to promote bone growth has not yet been elucidated.

Therefore, in the present invention, it was firstly established that a composition containing curcumin as an active ingredient has excellent bone formation, that is, an activity of promoting bone growth. It is believed that this method restores bone loss and promotes the growth of bone length In fact, it has been shown that it not only inhibits bone resorption but also increases bone formation.

Therefore, the present invention can provide a composition for promoting bone growth containing curcumin as an active ingredient.

Curcumin contained in the composition of the present invention can be used as long as it is sold in the market, but it can be preferably extracted from natural sources. More preferably, it can be extracted and purified from turmeric using water or an organic solvent using a purification method known to a person skilled in the art to which the present invention belongs. Also, the portion of turmeric which can be used to obtain curcumin at this time may be the whole, but preferably roots of turmeric can be used.

The organic solvent may be a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropanol, isopropanol, and the like. Butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane, and cyclohexane. Can be used alone or in combination.

The curcumin of the present invention can be prepared from natural products according to a conventional method for producing an extract. Specific examples thereof include a cold extract extraction method, a hot extraction extraction method, a hot water extraction method, and the like. The extractant, Can be used.

In addition, the extract extracted with the solvent may be filtered, concentrated or dried to remove the solvent, and may be subjected to both filtration, concentration, and drying. Specifically, the filtration can be performed using a filter paper or a vacuum filter, and the concentration can be reduced by using a vacuum concentrator, for example, a rotary evaporator. The drying can be performed by, for example, freeze drying. Curcumin obtained from the natural product can be completely removed through concentration and hot air drying. Curcumin, which has completely removed the moisture, can be used in powder form, or the powder can be used in distilled water or a conventional solvent .

In one embodiment of the present invention, the turmeric was dried by hot air and then pulverized to prepare a powder. 95% ethanol was added to the powder to obtain a 95% ethanol extract, which was then concentrated by distillation at 40 ° C to obtain concentrated curcumin- Of ethanol extract.

As described above, Curcumin according to the present invention has an excellent effect of promoting bone growth, and is effective in preventing bone loss and promoting bone formation.

That is, according to one embodiment of the present invention, in order to investigate whether curcumin has an activity of promoting bone growth, an animal model in which bone loss is induced is prepared, curcumin is administered to the animal model, Femur analysis, bone density analysis, and relative activity of ALP as a marker of osteoblast differentiation showed that bone resorption was restored in the curcumin-treated group and bone length was promoted in the animal model in which bone loss was induced The bone mass of the epiphysis was also significantly increased, and the distal metaphysis was also noticeably restored. In addition, the activity of ALP, which is a differentiation marker of osteoblast, was highly dependent on curcumin concentration. Therefore, the inventors of the present invention found that the curcumin of the present invention can be used as an anabolic reagent capable of preventing bone loss and promoting bone formation (see Example 2).

Therefore, the present invention can provide a composition for promoting bone growth containing curcumin as an active ingredient, and also provide a composition for preventing or treating bone diseases containing curcumin as an active ingredient.

The bone diseases to which the composition according to the present invention can be prevented or treated include, but are not limited to, general bone diseases, preferably osteoporosis, rheumatoid arthritis, osteoarthritis, degenerative arthritis, disc, osteomalacia, Paget's disease, Fibrous dysplasia, and more preferably osteoporosis.

In addition, the composition containing the curcumin as an active ingredient according to the present invention may contain a pharmaceutically effective amount of Curcumin alone or may include one or more pharmaceutically acceptable carriers, excipients or diluents. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to prevent, ameliorate, and treat bone diseases.

The pharmaceutically effective amount of curcumin according to the present invention is 0.5 to 100 mg / day / kg body weight, preferably 5 to 10 mg / day / kg body weight. However, the pharmaceutically effective amount may be appropriately changed according to the degree of the bone disease symptoms, the age, body weight, health condition, sex, administration route and treatment period of the patient.

The term "pharmaceutically acceptable" as used herein refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction such as gastrointestinal disorder, dizziness, or the like when administered to humans. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. Further, it may further include a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent and an antiseptic agent.

In addition, the compositions of the present invention may be formulated using methods known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatine capsules, sterile injectable solutions, sterile powders.

The composition for promoting bone growth according to the present invention may be administered through various routes including oral, transdermal, subcutaneous, intravenous, or muscular, and the dose of the active ingredient may be varied depending on the administration route, age, sex, And the like. In addition, the composition for promoting bone growth of the present invention may be administered in combination with a known compound having an effect of preventing, ameliorating or treating bone diseases.

Accordingly, the present invention can provide a drug for bone diseases, which comprises a composition containing curcumin as an active ingredient.

Furthermore, since the composition for promoting bone growth of the present invention can be added to a food for the purpose of prevention and improvement of bone disease, the composition of the present invention can be used as a food composition for prevention and improvement of bone diseases.

Therefore, the composition of the present invention can be easily utilized as a food which is effective for prevention and improvement of symptoms of bone disease, for example, as a raw material, additives, food additives, functional foods or beverages of foods.

As used herein, the term "food" means a natural product or a processed product containing one or more nutrients, preferably a state capable of being directly eaten through a certain degree of processing, , Food, food additives, functional foods and beverages.

Foods to which the composition according to the present invention can be added include, for example, various foods, beverages, gums, tea, vitamin complexes, and functional foods. In addition, in the present invention, the food may include special nutritive foods (e.g., crude oil, spirits, baby food, etc.), meat products, fish meat products, tofu, mackerel, noodles (Such as soy sauce, soybean paste, kochujang, mixed potatoes), sauces, confectionery (eg, snacks), candies, chocolate, gums, ice cream, milk products (eg, fermented milk, cheese, But are not limited to, pickled foods (various kinds of kimchi, pickles, etc.), beverages (e.g., fruit drinks, vegetable beverages, beverages, fermented beverages and the like) and natural seasonings (e.g. The food, beverage or food additive may be prepared by a conventional production method.

The above-mentioned "functional food" refers to a food group which is imparted with added value to function and express the function of the food by physical, biochemical or biotechnological techniques, or to control the bio-defense rhythm of the food composition, Refers to a food prepared by processing a body so as to sufficiently express the body's control function on the body, such as recovery, and the like. Specifically, it may be a health functional food. The functional food may include a food-acceptable food-aid additive, and may further comprise suitable carriers, excipients and diluents conventionally used in the production of functional foods.

In the present invention, the term "beverage " means a general term for drinking or enjoying a taste, and includes a functional beverage. The beverage is not particularly limited as long as it contains the composition for promoting bone growth according to the present invention as an essential ingredient and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages.

Furthermore, the food containing the composition of the present invention in addition to the above-mentioned composition can be used as a food such as various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers (cheese, And carbonates used in alginic acid and its salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonated drinks, etc., and these components may be used independently or in combination Can be used.

In the food comprising the composition containing curcumin of the present invention, the amount of the composition according to the present invention may be 0.001% by weight to 90% by weight, preferably 0.1% by weight or less, And may be contained in an amount of 0.001 g to 2 g, preferably 0.01 g to 0.1 g, based on 100 ml of a beverage. However, for the purpose of health and hygiene or for the purpose of health control The active ingredient may be used in an amount in excess of the above range because there is no problem in terms of safety. Therefore, the scope of the present invention is not limited to the above range.

Therefore, the present invention can provide a health functional food containing Curcumin according to the present invention as an active ingredient for promoting bone growth or preventing and improving osteopathy, and the form of the food is not limited thereto, Powders, granules, tablets, capsules or beverages.

Hereinafter, the present invention will be described in more detail by way of examples. It will be apparent to those skilled in the art that these embodiments are merely illustrative of the present invention and that the scope of the present invention is not limited to these embodiments.

From turbulence Curcumin  detach

In order to obtain curcumin which is a component contained in a large amount of turmeric, the roots of the roasted pepper were first washed and finely pulverized. Then, the roots were dried in hot air at 80 ° C to have a water content of 10% or less, The process of immersing in ethanol for 24 hours was repeated three times to obtain an ethanol extract of a sulfurized root. Thereafter, the ethanol extraction filtrate was concentrated at 40 DEG C using a rotary evaporator to obtain an ethanol extract of turmeric containing curcumin.

Curcumin  Measurement of effect on bone growth

To determine if curcumin is effective in bone growth, a 6-week-old female C57BL / 6 mouse was prepared as an ovariectomy to make a postmenopausal model. The ovariectomy was divided into two groups, (9.5 μg / g of body weight / d) dissolved in PBS and 0.5 ml of PBS (Phosphate buffered saline) were intragastrically injected into the other group. As a control group, normal mice without ovariectomy were divided into two groups as described above, and groups in which curcumin and PBS were respectively injected were used. After 8 weeks, the femurs of each mouse were cut out and fixed in formalin for 1 week and analyzed by X-ray spectroscopy. Bone mineral density (BMD) was measured using a real-time image processing and measurement system (ZET-1).

In order to measure the activity of Alkaline phosphatase (ALP), which is an osteoblast differentiation marker, Mesenchymal Stem Cells (MSCs) isolated from bone marrow cells of ovariectomized mice were inoculated into osteogenic differentiation induction medium (10% FBS , Α-MEM medium containing 100 μg / ml penicillin, 100 μg / ml streptomycin, 12 μM L-glutamine, 50 μM ascorbic acid, and 10 mM β-glycerophosphate), and the medium was changed every three days. At this time, 2 [mu] M and 4 [mu] M of curcumin were added to the cells in the culturing step. After 12 days of culture, the cells were harvested, pulverized and centrifuged. The supernatant was collected and the ALP activity was measured by fluorimetric analysis using AtarBright Alkaline Phosphatase Detection kit (MT-1000, Sigma Aldrich).

As a result, as shown in FIG. 1 and FIG. 2, in the case of Curcumin-treated group in the mouse (OVX) induced osteoporosis by ovariectomy, not only the bone loss due to the estrogen hormone deficiency was restored, . As shown in FIG. 3, the bone mass of epiphysis was increased when curcumin was administered to both the mouse group (Sham) and the ovariectomized mouse group (OVX) without ovariectomy Distal metaphysis, which showed a significant difference in bone mass compared to the control group at ovariectomized period, was remarkably restored when curcumin was administered, and curcumin (curcumin ) Significantly increased the total bone length. Also, as shown in Fig. 4, since the relative activity of ALP is increased depending on the concentration of Curcumin, curcumin inhibits bone resorption and increases bone formation to prevent bone loss It can be seen that there is an effect that can be achieved.

The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (8)

A composition for promoting the differentiation of mesenchymal stem cells into osteoblasts in vitro containing curcumin as an active ingredient. The method according to claim 1,
Wherein the curcumin is extracted by adding water or an organic solvent to the turmeric. 3. The method of claim 2,
Wherein the organic solvent is a lower alcohol having 1 to 4 carbon atoms. delete delete delete delete delete

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