KR101306876B1 - Composition for prevention and treatment of bone diseases comprising extract of hovenia dulcis thunb. - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of bone diseases, which contains the extract as an active ingredient. The extract of the present invention is a natural product, has no side effects, promotes formation rather than suppression of bone degradation, and is effective in treating osteoporosis and related diseases by supplementing disadvantages of existing bone degradation inhibitors.

Description

COMPOSITION FOR PREVENTION AND TREATMENT OF BONE DISEASES COMPRISING EXTRACT OF HOVENIA DULCIS THUNB.}

The present invention relates to a composition for the prevention and treatment of bone diseases, which contains the extract as an active ingredient.

Osteoporosis is a disease in which there is no change in the chemical composition of the bone and a decrease in bone mass in the unit volume, which can easily cause fracture even in a slight impact. Currently, the majority of osteoporosis treatment drugs to alleviate the symptoms or prevent the progression of the goal is mainly antiresorptive drug (antiresorptive drug) to delay the action of bone loss. Currently, osteoporosis treatment drugs are bisphosphonates, which inhibit bone loss by weakening the functions of osteoclasts (bone resorption-related cells). Merck's Fosamax, Procter Gamble, And "Actonel". However, these treatments do not promote the formation of bones, but as a decomposition inhibitor, it is necessary to replace the bone because it can induce additional fractures in continuous use.

Recently, as the functions of various proteins and genes related to bone formation have been revealed, various attempts at the development of 'bone formation promoters' targeting these proteins and genes have been made in multinational pharmaceutical companies or in Korea. / β-catenin signaling system has been shown to regulate bone growth and bone density since it has been reported that co-receptor co-receptor LRP5 is responsible for osteoporosis pseudoglioma syndrome (OPPG), a representative genetic disease caused by bone mineral density. Relevant research has been actively studied, and it is known that activation of the Wnt / β-catenin signaling system induces an increase in bone volume, and has been highlighted as an effective and safe drug treatment target in the treatment of osteoporosis (Boyden et al. N Engl. J. Med. 2002; Little et al. Am. J. Hum. Genet. 2002; Einhorn et al., Science Translational Medicine, 2010; Yavropoulous e t al., Exepert Review of Endocrinology and Metabolism, 2010; Wagner et al. Current Molecular Pharmacology, 2011). At present, no safe osteoporosis medication to treat bone formation has been developed, except for expensive and inapplicable Paratyroidhormone (PTH) . Therefore, the inventors of the present invention are able to activate the Wnt / β-catenin signaling system using Hoveniadulcis Thunb. To the present invention.

An object of the present invention to provide a composition for the prevention and treatment of bone disease using a natural earth, which can greatly help the osteoporosis and related diseases without side effects by supplementing the disadvantages of the existing bone breakdown inhibitors that make the bone loose will be.

In one embodiment, to achieve the above object, it provides a pharmaceutical composition for the prevention and treatment of bone diseases containing Hoveniadulcis Thunb. Extract as an active ingredient. In another embodiment, the bone disease is any one selected from the group consisting of, but not limited to, osteoporosis (osteoporosis), osteomalacia, rickets, fibrosis, aplastic bone disease and metabolic bone disease It provides a pharmaceutical composition for the prevention and treatment of. In another embodiment, the extract provides a pharmaceutical composition for the prevention and treatment of bone diseases, characterized in that to promote the activity of the Wnt / β-catenin signaling system. In another embodiment, the extract provides a pharmaceutical composition for the prevention and treatment of bone diseases, characterized in that to promote bone formation by Wnt / β-catenin signaling system activity. In another embodiment, the bone disease provides a pharmaceutical composition for the prevention and treatment of bone diseases, characterized in that osteoporosis (osteoporosis). In another embodiment, the dosage amount is 0.1 to 10g / kg provides a pharmaceutical composition for the prevention and treatment of bone diseases. In another embodiment, there is provided a pharmaceutical composition for the prevention and treatment of bone diseases, characterized in that oral, parenteral, intraarterial, intradermal, transdermal, intramuscular, intraperitoneal, intravenous, subcutaneous and intranasal administration.

In one embodiment, the present invention provides a food composition for improving and alleviating bone disease, containing the extract as an active ingredient. In another embodiment, the bone disease is any one selected from the group consisting of, but not limited to, osteoporosis (osteoporosis), osteomalacia, rickets, fibrosis, aplastic bone disease and metabolic bone disease It provides a food composition for improving and alleviating. In another embodiment, the extract provides a food composition for improving and alleviating bone disease, characterized in that to promote the activity of the Wnt / β-catenin signaling system. In another embodiment, the extract provides a food composition for improving and alleviating bone diseases, characterized in that to promote bone formation by Wnt / β-catenin signaling system activity. In another embodiment, the bone disease provides osteoporosis (osteoporosis), and provides a food composition for improving and alleviating bone diseases.

In addition to the above-described active ingredient for administration, it may be prepared by including one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, antioxidants, buffers And other conventional additives such as bacteriostatic agents can be added. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by a suitable method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.

The compositions of the present invention can be administered to humans or animals by a variety of routes, including parenteral, intraarterial, intradermal, transdermal, intramuscular, intraperitoneal, intravenous, subcutaneous, oral and intranasal routes of administration. Dosage varies depending on the weight, age, sex, health status, diet, time of administration, method of administration, rate of excretion, and severity of disease of the patient. The daily dosage of the composition is about 10 ng / kg to 10 mg / kg, preferably about 80 to 400 ng / kg, and more preferably, administered once or several times a day.

In the present invention, "party district" means the fruit or seeds of trees with gwabyeong of heotgae rhamnaceae (Hoveniadulcis Thunb.).

In the present invention, "bone disease" is a result of the imbalance between osteoclasts and osteoblasts in bone, but is not limited thereto. Bone damage, osteoporosis, osteomalacia, rickets disease, fibrous osteoarthritis caused by bone metastasis of cancer cells , Aplastic bone disease and metabolic bone disease (see Korean Patent Nos. 10-0399374 and 10-0720026).

The extract of the present invention is a natural product, has no side effects, promotes formation rather than suppression of bone degradation, and is effective in treating osteoporosis and related diseases by supplementing disadvantages of existing bone degradation inhibitors.

1 is a natural screening result of activating the Wnt / β-catenin signaling system.
Figure 2 is a result of measuring the transcription by β-catenin at the HEK-TOP spermatozoon extract.
Figure 3 is a result showing the protein increase of β-catenin through the extract.
Figure 4 is a photograph confirming the increase of β-catenin through the immunohistostaining method.
Figure 5 is a photograph showing the increase in the thickness of the headcap bone of the group treated with the extract.
Figure 6 is a graph showing the increase in the thickness of the head cover bone of the group treated with the extract.

Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

Example

Example  One. Preparation of natural extracts and Screening

HEK-TOP is a stable cell line with Topflash capable of measuring β-catenin reporters in HEK293. The cells were treated with 300 kinds of natural products at a concentration of 1 ug / ml, and after 24 hours, transcription by β-catenin was measured through a reporter (FIG. 1). Hoveniadulcis Thunb. Was selected as a substance to increase β-catenin-induced transcription through screening, and the reporter value was increased by measuring β-catenin-induced transcription again in HEK-TOP. It was confirmed (FIG. 2). The earthworm extract was obtained from Korea Plant Extract Bank.

Example  2. Confirm the efficacy of the earth through animal experiments

The primary osteoblasts (POB) were isolated from the calfria of four-day-old rats fed from Orient Bio, and after 5 ug / ml of sperm treated for 24 hours, it was confirmed that the protein of β-catenin increased (FIG. 3). ).

Induced differentiation in Calvaria of 4 day-old rats, 5 ug / ml of Schisandra chinensis extract was treated for 1 week. Through immunohistochemistry, it was confirmed that β-catenin was increased in the group treated with the extract of Schisandra chinensis (Figure 4). In addition, as a result of measuring the thickness it was confirmed that the thickness of the head cover bone in the group treated with the earth globe compared to the control group (Figs. 5 to 6).

Example 3 In Vivo Administration of Extracts for the Treatment of Bone Disease

The acute toxicity test was carried out as described below using specific pathogen-free (SPF) SD rats of 6 weeks old supplied from the experimental supply center. After two oral administrations of the extract of Example 1 at a dose of 1 g / kg to two animals in each group, the mortality, clinical symptoms, and weight changes of the animals were observed, and hematological and blood biochemical tests were performed. The necropsy was performed to visually check the tonic and thoracic organ abnormalities. As a result of the experiment, there were no clinical symptoms or dead animals in all animals treated with the test substance, and no toxic change was observed in weight change, blood test, blood biochemical test, and autopsy findings. As a result, it was confirmed that the extract of the present invention did not exhibit any toxicity at 1 g / kg or more in rats, and that the oral LDL was at least 1 g / kg.

Formulation example  One: Sanje  Produce

Earth Extract of Example 1 ----------------------------- 300 mg

Lactose ------------------------------------------------- 100 mg

Talc ------------------------------------------------- -10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  2: Preparation of tablets

Earth extract of Example 1 ----------------------------- 50 mg

Corn Starch ------------------------------------------- 100 mg

Lactose ------------------------------------------------- 100 mg

Magnesium Stearate ------------------------------------ 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  3: Manufacture of capsule

Earth Extract of Example 1 ------------------------------ 50 mg

Corn Starch ------------------------------------------- 100 mg

Lactose ------------------------------------------------- 100 mg

Magnesium Stearate ------------------------------------ 2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  4: Preparation of injection

Earth extract of Example 1 ----------------------------- 50 mg

Sterile Distilled Water for Injection

pH regulator ---------------------------------------------

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation example  5: Liquid  Produce

Earth Extract of Example 1 ----------------------------- 100 mg

Isomerized sugar ---------------------------------------------- 10 g

Mannitol ------------------------------------------------- 5 g

Purified water------------------------------------------------- Quantity

According to the conventional method for preparing a liquid, each component is added and dissolved in purified water, lemon flavor is added, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by adding purified water, and then filled in a brown bottle. The solution is prepared by sterilization.

Formulation example  6: Manufacture of health food

Earth Extract of Example 1 ---------------------------- 1000 mg

Vitamin Mixture -------------------------------------------

Vitamin A Acetate ------------------------------------ 70 μg

Vitamin E ---------------------------------------------- 1.0 mg

Vitamin B ₁ -------------------------------------------- 0.13 mg

Vitamin B ₂ -------------------------------------------- 0.15 mg

Vitamin B ₆ --------------------------------------------- 0.5 mg

Vitamin B ₁₂ --------------------------------------------- 0.2 μg

Vitamin C ----------------------------------------------- 10 Mg

Biotin ------------------------------------------------- 10 μg

Nicotinic Acid Amide ---------------------------------------- 1.7 mg

Folic acid ------------------------------------------------- --50 μg

Calcium Pantothenate -------------------------- 0.5 mg

Mineral mixture -------------------------------------------

Ferrous Sulfate -------------------------------------------- 1.75 mg

Zinc Oxide --------------------------------------------- 0.82 mg

Magnesium Carbonate ----------------------------------------- 25.3 mg

Potassium monophosphate -------------------------------------------- 15 mg

Dibasic calcium phosphate -------------------------------------------- 55 mg

Potassium Citrate --------------------------------------------- 90 mg

Calcium Carbonate ---------------------------------------------- 100 mg

Magnesium Chloride ----------------------------------------- 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Formulation example  7: Manufacture of health drinks

Earth Extract of Example 1 ------------------------------ 1000 mg

Citric Acid ------------------------------------------------ 1000 Mg

Oligosaccharide ------------------------------------------------ 100 g

Plum Concentrate 2 g

Taurine ------------------------------------------------- --- 1 g

Add purified water to the whole

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated for about 1 hour at 85 DEG C with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

While the present invention has been described with reference to exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. You will know. In addition, many modifications may be made to adapt a particular situation and material to the teachings of the invention without departing from the essential scope thereof. Accordingly, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention be construed as including all embodiments falling within the scope of the appended claims.

Claims (12)

Pharmaceutical composition for promoting bone formation containing Hoveniadulcis Thunb. Extract as an active ingredient. The method of claim 1,
A pharmaceutical composition for promoting bone formation, characterized in that to prevent or treat osteomalacia, rickets, fractures, fibrous osteoarthritis, aplastic bone disease or metabolic bone disease through promoting bone formation. The method of claim 1,
The extract is a pharmaceutical composition for promoting bone formation, characterized in that to promote the activity of the Wnt / β-catenin signaling system. delete delete The method of claim 1,
The dosage is 0.1 to 10g / kg pharmaceutical composition for promoting bone formation, characterized in that. The method of claim 1,
Oral, parenteral, intraarterial, intradermal, transdermal, intramuscular, intraperitoneal, intravenous, subcutaneous or intranasal administration pharmaceutical composition for promoting bone formation. Food composition for promoting bone formation containing the extract extract as an active ingredient. The method of claim 8,
Food composition for promoting bone formation, characterized in that to improve or alleviate osteomalacia, rickets, fractures, fibrous osteoarthritis, aplastic bone disease and metabolic bone disease through promoting bone formation. The method of claim 8,
The extract is a food composition for promoting bone formation, characterized in that to promote the activity of Wnt / β-catenin signaling system.
delete delete

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