KR102415187B1 - Composition for preventing or treating bone disease comprising a extract mixture of ulmus bark and cornus officinalis - Google Patents

Abstract

The present invention relates to a composition for preventing or treating bone diseases containing a mixed extract of milkweed and cornus oil as an active ingredient. As it was confirmed, the composition comprising the mixed extract of milkweed pyranthiaceae of the present invention as an active ingredient can prevent two diseases, osteoporosis and osteoarthritis, and effectively relieve symptoms to treat osteoporosis or osteoarthritis by a pharmaceutical preparation or health function It may be provided as food.

Description

A composition for preventing or treating bone disease comprising a complex extract of milk white skin and cornus oil as an active ingredient {Composition for preventing or treating bone disease comprising a extract mixture of ulmus bark and cornus officinalis}

The present invention relates to a composition for preventing, improving, or treating osteoporosis or osteoarthritis, comprising a mixed extract of milkweed and cornus oil as an active ingredient.

Bone tissue is a dense connective tissue surrounded by bone cells and hard calcium tissue around them, and has a mechanical function of support and muscle attachment. In addition, it is responsible for protecting living organs and bone marrow and preserving calcium and phosphorus ions to maintain homeostasis. Such bone tissue is composed of a cell matrix such as collagen and glycoprotein and various types of cells such as osteoblasts, osteoclasts, and osteocytes. Osteoblasts derived from bone marrow stromal cells play a major role in bone formation, and osteoclasts derived from hematopoietic stem cells are destroyed and are responsible for resorption of aged bone. Through the balanced action of bone formation and bone resorption, bone remodeling is maintained.

Bone metabolic disease occurs when the balance between osteoblasts and osteoclasts, which play a major role in maintaining bone remodeling, is abnormal. As a representative example of bone metabolic disease, there is osteoporosis, in which the bone resorption activity of osteoclasts increases compared to bone formation by osteoblasts, and as a result, total bone mass decreases, resulting in fractures even with a slight impact. say disease. To date, there is no effective treatment for osteoporosis, and prevention is emphasized. Currently, there are drugs such as bisphosphonates as the most widely used osteoporosis treatment in the world, but there are many side effects, so long-term administration is difficult, and there are disadvantages in that they do not play a big role in increasing bone density due to new bone formation.

Osteoarthritis (degenerative arthritis) is a degenerative disease that occurs gradually and irreversibly and reduces the quality of life. It is one of the most common degenerative diseases for elderly women. It is a representative degenerative disease that lowers the quality of life and consumes a lot of social costs such as treatment. Osteoarthritis treatments include analgesic anti-inflammatory drugs, hyaluronic acid treatments, autologous cell therapies, stem cell therapies, gene cell therapies, and artificial joints aimed at relieving pain, and there is no fundamental treatment other than artificial joint surgery.

Because of the nature of these two diseases, long-term use is required, so it is necessary to develop health functional foods and natural products derived from natural products rather than drugs with many side effects. In particular, there are many patients suffering from osteoporosis and osteoarthritis in the elderly, so it is necessary to develop health functional foods and natural medicines that can prevent, improve, and treat these two diseases at the same time.

Republic of Korea Patent Publication No. 10-2010-0004331 (published on Jan. 13, 2010)

An object of the present invention is to provide a mixed extract effective in preventing, improving and treating osteoporosis and osteoarthritis, which is a common problem in elderly women, at the same time, and a composition comprising the same as an active ingredient.

The present invention provides a pharmaceutical composition for the prevention or treatment of bone disease containing a complex extract of milkweed and Cornus officinalis as active ingredients.

In addition, the present invention provides a health food for the prevention or improvement of bone disease containing the complex extract of milkweed and Cornus officinalis as active ingredients.

According to the present disease, as it was confirmed that the mixed extract of Yubaekpisansuyu and Cornus officinalis has a great effect on the improvement of osteoporosis and osteoarthritis in cell experiments and animal experiments, the composition comprising the Yubaekpisansuyu mixed extract of the present invention as an active ingredient is osteoporosis and osteoarthritis It can prevent two diseases, and it can be provided as a pharmaceutical preparation or health functional food for treating osteoporosis or osteoarthritis by effectively alleviating symptoms.

Figure 1 is the result of confirming the osteoblast differentiation promoting effect of the raw material standardized cornus oil and milkweed extract and 5:5, 7:3 or 8:2 ratio of cornus and milkweed complex extract, Control: No differentiation induction, Mock: Induction of osteoblast differentiation.
Figure 2 is the result of confirming the osteoclast differentiation inhibitory effect of the standardized raw material standardized cornus oil and milkweed extract and 5:5, 7:3 or 8:2 ratio of cornus and milkweed complex extract, Control: No differentiation induction, Mock: Induction of osteoclast differentiation.
Figure 3 is the result of confirming the expression inhibitory effect of COX-2, MMP-3 and MMP-13, which are osteoarticular inflammatory factors of the cornus oil and milk white skin complex extract, Control: no inflammation, Mock: inflammation-inducing-negative control group.
Figure 4 is the result of confirming the bone density of the osteoporosis animal model administered with cornus oil and milk white skin complex extract, Sham: non-ovarian resection group, Control: ovariectomized group-OVX.
5 is a result of photographing the bone microstructure of an animal model of osteoporosis administered with cornus oil and milk white skin complex extract, Sham: non-ovarian resection group, Control: ovarian resection group-OVX.
Figure 6 is a graph analyzing the bone microstructure of an animal model of osteoporosis administered with cornus oil and milk white skin complex extract, Sham: non-ovarian group, Control: ovariectomized group-OVX.
Figure 7 is the result of analyzing the ICRS grade, Safranin O staining and bone microstructure of the osteoporosis animal model administered with cornus oil and milk white skin complex extract, Sham: no medial meniscus destabilization induction, Control: medial meniscus destabilization induction-MSM.

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

Various menopausal symptoms appear due to the rapid decrease of estrogen, a female hormone that appears after menopause, and in particular, osteoporosis and osteoarthritis are diseases that require continuous treatment and are therefore directly related to quality of life. Due to the recent rapid progress in Koreanization, the number of patients with these degenerative diseases is also greatly increasing. There is a treatment for osteoporosis, but it has the disadvantage that it cannot be used for a long time due to side effects, and there is no fundamental treatment for osteoarthritis other than pain control. Therefore, the inventors of the present invention have completed the present invention in order to provide a health functional food and natural medicine derived from a natural product that can be taken for a long time for both diseases.

The present invention can provide a pharmaceutical composition for the prevention or treatment of bone disease containing the complex extract of milkweed and Cornus officinalis as an active ingredient.

The Yubaekpi and Cornus officinalis complex extract may be mixed with Yubaekpi and Cornus oil in a weight ratio of 2:8 to 8:2, and more specifically, 5:5, 7:3 or 8:2 by weight, More preferably, it may be a complex extract mixed in a 5:5 weight ratio, but is not limited thereto.

The milkweed and cornus oil complex extract may be extracted with water, C1 to C4 alcohol, or a mixed solvent thereof.

The bone disease may be one or more selected from the group consisting of osteoporosis and osteoarthritis.

The milkweed extract and Cornus officinalis complex extract promotes the differentiation of osteoblasts and may inhibit the differentiation of osteoclasts. In addition, the milkweed and Cornus officinalis complex extract is an inflammatory factor COX-2, MMP-3 and MMP-13 It may be to inhibit expression.

In one embodiment of the present invention, the pharmaceutical composition for the prevention or treatment of bone disease containing the milkweed extract and Cornus officinalis complex extract as an active ingredient is prepared by injection, granules, powders, tablets, pills, capsules, suppositories, Any one formulation selected from the group consisting of gels, suspensions, emulsions, drops or liquids may be used.

In another embodiment of the present invention, the pharmaceutical composition for the prevention or treatment of bone disease containing milkweed and cornus extract as an active ingredient is an appropriate carrier, excipient, disintegrant, sweetener, coating agent commonly used in the manufacture of pharmaceutical compositions. , a swelling agent, a lubricant, a flavoring agent, an antioxidant, a buffer, a bacteriostatic agent, a diluent, a dispersant, a surfactant, a binder, and one or more additives selected from the group consisting of lubricants may be further included.

Specifically, carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil can be used, and solid preparations for oral administration include tablets, pills, powders, granules, and capsules. agent, and the like, and the solid preparation may be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, and the like in the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral use include suspensions, solutions, emulsions, syrups, and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included in addition to commonly used simple diluents such as water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base material for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

According to an embodiment of the present invention, the pharmaceutical composition is administered in a conventional manner via intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, intranasal, inhalational, topical, rectal, oral, intraocular or intradermal routes. can be administered to the subject.

Preferred dosages of the milkweed extract and Cornus officinalis complex extract may vary depending on the subject's condition and weight, the type and extent of disease, drug form, administration route and period, and may be appropriately selected by those skilled in the art. According to an embodiment of the present invention, although not limited thereto, the daily dose may be 0.01 to 200 mg/kg, specifically 0.1 to 200 mg/kg, and more specifically 0.1 to 100 mg/kg. Administration may be administered once a day or may be administered in several divided doses, thereby not limiting the scope of the present invention.

In the present invention, the 'subject' may be a mammal including a human, but is not limited to these examples.

In addition, the present invention can provide a health food for preventing or improving bone disease containing a complex extract of milkweed and cornflower as an active ingredient.

The health food is used together with other foods or food additives in addition to the milkweed and cornus oil complex extract, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be suitably determined according to the purpose of its use, for example, prophylactic, health or therapeutic treatment.

The effective dose of the compound contained in the health food may be used according to the effective dose of the therapeutic agent, but in the case of long-term intake for health and hygiene or health control, it may be less than or equal to the above range, It is clear that the ingredient can be used in an amount beyond the above range because there is no problem in terms of safety.

The type of health food is not particularly limited, and examples include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes.

Hereinafter, examples will be described in detail to help the understanding of the present invention. However, the following examples are merely illustrative of the content of the present invention, and the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.

<Example 1> Preparation of milk white skin and cornus oil complex extract

Milkweed skin and Cornus officinalis were extracted with 30% ethanol aqueous solution at 80° C. for 4 hours, left for about 20 hours, and then filtered with a filter paper. Each extract powder was prepared by freeze-drying the filtrate. The mixed extract of Yubaekpi and Cornus officinalis was prepared by mixing Yubaekpi extract powder and Cornushu oil extract powder in a weight ratio of 5:5.

<Example 2> Confirmation of osteoporosis and osteoarthritis improvement effect of milk white skin and cornflower oil complex extract in vitro

1. Confirmation of efficacy of milk baekpi and cornus oil complex extract for osteoporosis and osteoarthritis

In order to confirm the differentiation effect of milky white and Cornus officinalis complex extracts on the differentiation capacity (ALP activity) of osteoblasts (MC3T3-E1), the origin of osteoblasts, into osteoblasts, standardized raw material standardized cornus oil and milkweed alone or by ratio The complex extract (5:5, 7:3, 8:2) was treated in the osteoblast cell line MC3T3-E1 at a concentration of 10 μg/ml, respectively, and ALP activity analysis was performed 3 days later to confirm the change in osteoblast differentiation degree.

As a result, as shown in FIG. 1 , it was confirmed that in the cell group treated with the MC3T3-E1 cells, which are osteoblast progenitor cells, the complex extracts of milk baekpi and cornusflower improved differentiation promotion of osteoblasts compared to the control group treated with the single extract.

In addition, in order to confirm the osteoclast differentiation effect of the milk white skin and cornflower complex extract on the differentiation ability of monocytes, the origin cells of osteoclasts, into osteoclasts, primary monocytes, the source cells of osteoclasts, from the bone marrow of 6-week-old mice. After separation and culture, M-CSF (30 ng/ml) and RANKL (50 ng/ml) were treated for 3 days to induce osteoclast differentiation.

After that, TRAP activity analysis was performed after 6 days by treating primary monocytes induced by differentiation at a concentration of 10 μg/ml with single or ratio complex extracts (5:5, 7:3, 8:2) of standardized raw milk white skin and cornus oil. Thus, the inhibitory effect on osteoclast differentiation was confirmed.

As a result, as shown in FIG. 2 , an improved osteoclast differentiation inhibitory effect was confirmed in the primary monocyte cell group treated with the milk white skin and cornflower complex extract compared to the control group treated with the single extract.

2. Confirmation of efficacy of milk white blood and cornus oil complex extract in chondrocytes isolated from osteoarthritis model

In order to confirm the osteoarthritis improvement effect, primary chondrocytes were isolated from the cartilage of 5-day-old mice, and cells were cultured and then treated with interleukin-1β (Interlukin-1β, IL-1β) to prepare an osteoarthritis cell model.

Changes in the expression level of chondrocyte inflammatory factors COX-2, MMP-3, and MMP-13 by treatment with a complex extract (5:5) of milkweed and cornflower oil in an osteoarthritis cell model at concentrations of 2, 10 and 50 μg/ml was quantified by real-time RT-PCR method to confirm the osteoarthritis improvement effect of milk baekpi and cornus oil complex extract.

As a result, it was confirmed that the expression level of the osteoarthritis inflammatory factor was remarkably suppressed as shown in FIG. 3 .

From the above results, it was confirmed that the milky white extract and Cornus officinalis complex extract has an effect on improving osteoporosis by promoting osteoblast differentiation and inhibiting osteoclast differentiation, and suppressing the expression level of inflammatory factors that cause osteoarthritis, thereby improving osteoarthritis. became

<Example 3> Confirmation of osteoporosis and osteoarthritis improvement effect of milk baekpi and Cornus officinalis complex extract in vivo

1. Confirmation of the effectiveness of milk baekpi and Cornus officinalis complex extract in osteoporosis mouse model

Osteoporosis animal model was obtained by extracting milkweed and cornus oil from female ovariectomized ddY mice (OVX: mouse with laparotomy and ovarian removal) and sham-operated ddY female mice (Sham: mouse without ovariectomy after laparotomy) (5:5). was mixed with feed at doses of 100 and 200 mg/kg/day, and Bone Balance (150 mg/kg/day), a health functional food for improving osteoporosis, was administered as a positive control group, and the amount of change in bone density (BMD) after 12 weeks of breeding was investigated.

As a result, as shown in FIG. 4 , the effect of inhibiting bone density loss due to osteoporosis induction was confirmed in the dry season bone balance, which is good for bone health, and the complex extract (200 mg/kg/day), which are test substances, milk white skin. .

In addition, to investigate the effect of functional raw materials on bone, bone mineral density was checked for the shin (Femur) and tibia (Tibia) of the mouse using the PIXI-mus bone densitometer device, and all mouse objects Group separation was performed so that there was no statistically significant difference in weight between groups by measuring the star weight.

As a result, as shown in FIGS. 5 and 6, the bone microstructure density of the femur (Femur) of the OVX mouse from which the ovary was removed compared to a normal Shame mouse without removal of the ovary as shown in FIGS. The bone volume ratio, cancellous bone trabecular thickness, and the number of cancellous bone trabeculae were also significantly lower, and the cancellous bone trabecular space was found to be high. On the other hand, in the experimental group administered at 200 mg/kg/day of milkweed and cornus extract (5:5) for 12 weeks, the decrease in bone density and density of bone microstructure caused by menopause was suppressed, and the volume ratio of bones and cancellous bone It was confirmed that both the decrease in the thickness of soju, the number of cancellous bone trabeculae, and the increase in the trabecular trabecular space were suppressed.

From the above results, compared to Bone Balance, which is a health functional food for improving osteoporosis currently on the market, it was confirmed that milk baekpi and Cornus officinalis complex extract (5:5) showed an excellent osteoporosis improvement effect.

2. Confirmation of effectiveness of milk baekpi and Cornus officinalis complex extract in osteoarthritis mouse model

The medial meniscus ligament was removed from the knee joint of 12-week-old medial meniscus-induced OA mice (DMM) by micro surgery to destabilize the cartilage and induce degenerative arthritis. A mouse model of osteoarthritis was prepared.

Milkweed and Cornus officinalis complex extract (5:5) was mixed and administered to feed at doses of 100 and 200 mg/kg/day, and as a positive control, MSM (150 mg/kg/day), which is currently marketed as a health food for improving osteoarthritis After 10 weeks of breeding, the degree of cartilage degeneration of the joints through micro-CT and Safranin O staining were used to confirm the degree of cartilage degeneration through ICRS grade analysis. In addition, positive and negative control experiments were performed identically on Sham mice.

As a result, as shown in FIG. 7, cartilage damage and destruction were confirmed in the micro-CT imaging results 10 weeks after the joint of a mouse (DMM induced OA mouse; DMM) induced in cartilage destabilization, The inhibitory effect of degenerative osteoarthritis was confirmed at 200 mg/kg/day of the test substances, milk baekpi and Cornus officinalis complex extract (5:5), at a level similar to that of MSM, a good health functional food.

From the above results, it was confirmed that the milk white skin and cornflower complex extract can provide a functional raw material that can protect bones and joints and improve osteoporosis and arthritis.

As described above in detail a specific part of the present invention, for those of ordinary skill in the art, it is clear that this specific description is only a preferred embodiment, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (7)

A pharmaceutical composition for the prevention or treatment of osteoporosis or osteoarthritis, comprising as an active ingredient a mixture of extract powder obtained by extracting milkweed and cornus oil with an aqueous ethanol solution in a weight ratio of 5:5. delete [Claim 2] The pharmaceutical composition for preventing or treating osteoporosis or osteoarthritis according to claim 1, wherein the milkweed and cornus oil complex extract is extracted with water, C1 to C4 alcohol, or a mixed solvent thereof. delete The pharmaceutical composition for preventing or treating osteoporosis or osteoarthritis according to claim 1, wherein the milk white skin and cornflower complex extract promotes the differentiation of osteoblasts and inhibits the differentiation of osteoclasts. [Claim 2] The pharmaceutical composition for preventing or treating osteoporosis or osteoarthritis according to claim 1, wherein the milkweed extract and Cornus officinalis complex extract inhibits the expression of inflammatory factors COX-2, MMP-3 and MMP-13. A health food for the prevention or improvement of osteoporosis or osteoarthritis, containing as an active ingredient a mixture of extract powders extracted from milkweed skin and cornus oil with an aqueous ethanol solution in a 5:5 weight ratio.

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