KR102641021B1 - A composition for prevention and treatment of osteoporosis comprising extract from wheat bran - Google Patents

Abstract

The present invention relates to a composition for preventing or treating osteoporosis containing a wheat bran extract, a method for preventing or treating osteoporosis comprising administering the pharmaceutical composition, and a food composition and feed composition for improving osteoporosis containing the extract. . The wheat bran extract of the present invention not only inhibits the differentiation of osteoclasts, which represent bone homeostasis disorders, but also promotes the differentiation of osteoblasts, so it can be used for the prevention, improvement or treatment of osteoporosis, or in food and medicine. You can.

Description

{A composition for prevention and treatment of osteoporosis comprising extract from wheat bran}

The present invention relates to a composition for preventing or treating osteoporosis containing a wheat bran extract. Specifically, a pharmaceutical composition containing a wheat bran extract for preventing or treating osteoporosis; It relates to a method for preventing or treating osteoporosis comprising administering the pharmaceutical composition, and a food composition and feed composition for improving osteoporosis containing the extract.

Osteoporosis is one of the skeletal diseases in which the amount of bone decreases and the strength of the bone becomes weak, making it easy to fracture. It is a problem because it limits activity, and is known to account for about 15% of deaths in the elderly.

Causes of osteoporosis include age, differences in basic bone mass, early menopause or low levels of estrogen, smoking, and medications such as steroids. In particular, in women, bone loss continues after the age of 30, and when they reach menopause, hormone levels decrease. Bone loss progresses rapidly due to the change. In other words, when menopause is reached, the concentration of estrogen rapidly decreases, and as a result, the activity of osteoclasts increases, the amount of calcium contained in the bone decreases, and the structure that maintains the shape of the bone weakens.

To treat such osteoporosis, hormones, alendronate, calcitonin, raloxifene, Na-F, calcitriol, or bisphosphonate preparations are administered. However, since the treatment of osteoporosis is a disease that requires a long-term treatment period, long-term use of conventional drugs increases the possibility of side effects such as urinary stones, endometrial cancer, and breast cancer.

Calcium supplements used as first-generation osteoporosis treatments have been reported to have minimal effectiveness, and hormone therapy using estrogen or calcitonin has been reported to be unsafe in terms of safety (Jang JS. Osteoporotic fracture-Medical treatment. Journal of the Korean Fracture Society. 2010;23(3):326-340). In particular, hormone therapy increases bone density, but side effects such as breast cancer, myocardial infarction, and venous thrombosis have been reported (Rossouw JE et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477). Bisphosphonate bone resorption inhibitors, which are currently widely used, may cause lesions in the upper respiratory tract if administered incorrectly (Jang JS. Osteoporotic fracture-Medical treatment. Journal of the Korean Fracture Society. 2010;23(3):326-340). Osteoporosis is a disease that requires long-term drug administration, so the development of new substances with guaranteed safety and efficacy is urgently needed.

Accordingly, there is an urgent need for the development of treatments with less toxicity and side effects. Recently, alternative therapy research and various extracts using active ingredients derived from natural products such as herbal medicine and food can promote bone formation while minimizing bone loss without other side effects. Manufacturing methods are being developed. However, the development of natural pharmaceutical compositions or their raw materials that have excellent effects on preventing and improving osteoporosis and have fewer side effects than existing synthetic pharmaceutical compositions is still insufficient.

Against this background, the present inventors have made intensive research efforts to develop a treatment for osteoporosis using ingredients derived from natural products, and as a result, wheat bran extract can be used as a preventive and treatment agent for osteoporosis by inhibiting the activity of osteoclasts and promoting differentiation into osteoblasts. It was confirmed that this was the case, and the present invention was completed.

One object of the present invention is to provide a pharmaceutical composition for preventing or treating osteoporosis containing wheat bran extract as an active ingredient.

Another object of the present invention is to provide a method for preventing or treating osteoporosis comprising administering the pharmaceutical composition to an entity other than a human.

Another object of the present invention is to provide a food composition for preventing or improving osteoporosis containing wheat bran extract as an active ingredient.

Another object of the present invention is to provide a feed composition for preventing or improving osteoporosis containing wheat bran extract as an active ingredient.

This is explained in detail as follows. Meanwhile, each description and embodiment disclosed in the present invention may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in the present invention fall within the scope of the present invention. Additionally, the scope of the present invention cannot be considered limited by the specific description described below.

In one aspect of the present invention, in order to achieve the above-mentioned object, the present invention provides a pharmaceutical composition for preventing or treating osteoporosis containing wheat bran extract as an active ingredient.

The term "wheat" in the present invention is an annual herb of the Triticum genus of the Gramineae family and is a crop cultivated worldwide. Among about 22 types of wheat, common wheat ( Triticum aestivum ) occupies 90% of the world's cultivated area, and all wheat grown in Korea is common wheat. The wheat grain is structurally composed of the germ, endosperm, and bran layers. In the present invention, "bran" refers to a by-product containing the outer skin and a slight aleurone layer that is removed during polishing or milling of grains, etc. It belongs to the bran layer of the structure of the wheat grain and accounts for about 14%.

In the present invention, the wheat may be purchased and used commercially, or may be used as wheat collected or cultivated in nature, but is not limited thereto. In the present invention, the variety of wheat used is “Ariheuk,” a colored wheat, which is one of the varieties currently being expanded, and was produced at the National Institute of Crop Science in 2019.

In the present invention, the wheat bran extract can be used to prevent, treat or improve osteoporosis.

As used herein, the term "extract" refers to a liquid component obtained by immersing the desired substance in various solvents and then extracting it at room temperature or at a heated state for a certain period of time, and a solid component obtained by removing the solvent from the liquid component. means. In addition, in addition to the above results, it can be comprehensively interpreted to include all dilutions of the results, concentrates thereof, crude preparations, purifications, etc. of the above results. Accordingly, the wheat bran extract provided by the present invention is an extract obtained by extracting the wheat bran, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a crude product or purified product of the extract, or a mixture thereof. It can be interpreted as including the extract itself and all formulations of extract that can be formed using the extract.

The extraction method for the wheat bran extract of the present invention is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, and reflux extraction, which may be performed alone or by combining two or more methods.

The type of solvent used for the extraction is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the extraction solvent include water, alcohol, or a mixed solvent thereof, and these may be used alone or in a mixture of one or more kinds, and specifically, water may be used. When alcohol is used as a solvent, alcohol having 1 to 4 carbon atoms can be specifically used.

Additionally, the extract may be prepared and used in dry powder form after extraction, but is not limited thereto.

As used herein, the term “osteoporosis” refers to a condition in which bone quantity decreases and bone strength weakens due to qualitative changes, making fractures more likely to occur.

The wheat bran extract provided by the present invention can be used to prevent or treat osteoporosis by inhibiting the activity of osteoclasts.

Additionally, the wheat bran extract provided by the present invention can be used to prevent or treat osteoporosis by promoting differentiation of osteoblasts.

As used herein, the term “prevention” refers to any action that inhibits or delays the onset of osteoporosis by administering a pharmaceutical composition containing the wheat bran extract of the present invention.

As used herein, the term “treatment” refers to any action in which the symptoms of an individual suspected or affected by osteoporosis are improved or beneficially altered by administration of the pharmaceutical composition.

The pharmaceutical composition of the present invention may contain 0.001 to 80% by weight of the wheat bran extract, specifically 0.001 to 70%, and more specifically 0.001 to 60% by weight based on the total weight of the composition, but is not limited thereto.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent commonly used in the preparation of pharmaceutical compositions, and the carrier may include a non-naturally occurring carrier. You can.

As used herein, the term “pharmaceutically acceptable” means that the pharmaceutical composition exhibits non-toxic properties to cells or humans exposed to it.

Specifically, the pharmaceutical composition may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods. You can. In the present invention, carriers, excipients, and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, and cal. Examples include calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient, such as starch, calcium carbonate, sucrose, or lactose. It is prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, and syrups, and may contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives in addition to the commonly used simple diluents such as water and liquid paraffin. there is. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurin, glycerogeratin, etc. can be used.

In the present invention, the prevention or treatment of osteoporosis may be achieved by the extract inhibiting the activity of osteoclasts and inducing differentiation into osteoblasts.

In one example of the present invention, it was confirmed that the water extract of wheat bran has excellent osteoclast activity inhibition ability (Figure 1).

Additionally, in one embodiment of the present invention, it was confirmed that the alcohol extract of wheat bran has the ability to form osteoblasts (Figure 2)

Therefore, the wheat bran extract provided by the present invention can be effectively used in the prevention or treatment of osteoporosis.

Another aspect of the present invention for achieving the above object provides a method for preventing or treating osteoporosis, including the step of administering the pharmaceutical composition to an individual other than a human who is suffering from or is likely to develop osteoporosis.

At this time, the definitions of the terms “wheat”, “bran”, “extract”, “prevention” and “treatment” are as described above.

As used herein, the term “administration” refers to the act of introducing a composition comprising the wheat bran extract into a subject by an appropriate method.

The term "individual" in the present invention refers to all animals such as rats, mice, and livestock, including humans, that have or may develop osteoporosis. As a specific example, it may be a mammal, including humans.

The method for preventing or treating osteoporosis of the present invention may specifically include administering a pharmaceutical composition for preventing or treating osteoporosis containing a wheat bran extract in a pharmaceutically effective amount to an entity other than a human.

As used herein, the term "pharmaceutically effective amount" refers to an amount that is sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is determined by the patient's gender. , factors including age, weight, health status, type and severity of the disease, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, drugs combined or used simultaneously, and other medical It can be easily determined by a person skilled in the art according to factors well known in the art. Specifically, the composition of the present invention can be administered at a dose of 0.0001 to 100 mg/kg, more specifically, 0.001 to 100 mg/kg per day, based on solid content, and the administration is administered once a day or divided several times. You may.

The pharmaceutical composition 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. And it can be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without side effects, and can be easily determined by a person skilled in the art.

In addition, the pharmaceutical composition can be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) depending on the desired method, and the dosage is determined by the patient's condition and weight, and the degree of the disease. , it varies depending on the drug form, administration route and time, but can be appropriately selected by a person skilled in the art.

Another aspect of the present invention for achieving the above object provides a food composition for preventing or improving osteoporosis containing a wheat bran extract.

At this time, the definitions of the terms “wheat,” “bran,” “extract,” and “prevention” are as described above.

As used herein, the term “improvement” refers to any action that results in at least a reduction in the severity of symptoms, for example, parameters associated with the condition being treated by administration of a composition comprising the wheat bran extract.

As used herein, “food” refers to meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, and alcoholic beverages. , vitamin complexes, health functional foods, and health foods, etc., and include all foods in the conventional sense.

Since the food composition of the present invention is derived from wheat, which can be consumed on a daily basis, it can be expected to have a high lung cancer improvement effect, so it can be very useful for health promotion purposes.

The above-mentioned health functional food (functional food) is the same term as food for special health use (FoSHU), and is a medicine processed to efficiently exhibit bioregulatory functions in addition to nutritional supply, with high medical effects. It means food. Here, ‘function’ means controlling nutrients for the structure and function of the human body or obtaining useful effects for health purposes, such as physiological effects. The food of the present invention can be manufactured by methods commonly used in the industry, and can be manufactured by adding raw materials and ingredients commonly added in the industry. Additionally, the food formulation can be manufactured without limitation as long as it is a formulation recognized as a food.

The food composition of the present invention can be manufactured in various types of formulations, and unlike general drugs, it is made from natural products and has the advantage of not having side effects that may occur when taking the drug for a long period of time, and is excellent in portability, so the present invention Foods can be consumed as supplements to improve the effect of osteoporosis.

The above-mentioned health food refers to food that has a more active health maintenance or promotion effect compared to general food, and health supplement food refers to food for the purpose of health supplementation. In some cases, the terms health functional food, health food, and health supplement are used interchangeably.

Specifically, the health functional food is a food prepared by adding the composition of the present invention to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspending it, and consuming it may cause certain health problems. It means bringing about an effect, but unlike regular drugs, it has the advantage of not having any side effects that may occur when taking the drug for a long time since it is made from food.

The food composition may further include a physiologically acceptable carrier. The type of carrier is not particularly limited and any carrier commonly used in the art can be used.

Additionally, the food composition may contain additional ingredients that are commonly used in food compositions to improve smell, taste, vision, etc. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, etc. Additionally, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chromium (Cr); and amino acids such as lysine, tryptophan, cysteine, and valine.

In addition, the food composition contains preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching powder, high bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxide) roxitoluene (BHT), etc.), colorants (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG monosodium glutamate, etc.), sweeteners (dulcine, cyclemate, saccharin) , sodium, etc.), flavorings (vanillin, lactones, etc.), leavening agents (alum, D-potassium hydrogen tartrate, etc.), strengtheners, emulsifiers, thickeners (grease), coating agents, gum base agents, anti-foam agents, solvents, improvers, etc. May contain food additives. The additives can be selected depending on the type of food and used in an appropriate amount.

As an example of the food composition of the present invention, it can be used as a health drink composition, and in this case, it can contain various flavoring agents or natural carbohydrates as additional ingredients like ordinary drinks. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; polysaccharides such as dextrins and cyclodextrins; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol. Sweeteners include natural sweeteners such as thaumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame can be used. The ratio of the natural carbohydrate may be generally about 0.01 to 0.04 g, specifically, about 0.02 to 0.03 g per 100 ml of the health drink composition of the present invention.

In addition to the above, the health drink composition includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, It may contain alcohol or carbonating agent. Additionally, it may contain pulp for the production of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients can be used independently or in combination.

The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health drink composition of the present invention.

Another aspect of the present invention for achieving the above object provides a feed composition for preventing or improving osteoporosis containing wheat bran extract.

At this time, the definitions of the terms “wheat,” “bran,” “extract,” “osteoporosis,” “prevention,” and “improvement” are as described above.

Since the wheat bran extract according to the present invention exhibits excellent osteoclast differentiation inhibition and osteoblast formation ability, it can be included in a feed composition for the purpose of preventing or improving osteoporosis, and the feed composition can be consumed by animals on a daily basis. High effectiveness in preventing or improving osteoporosis can be expected.

As used herein, the term "feed" means any natural or artificial diet, meal, etc., or a component of the meal, for or suitable for eating, ingestion, and digestion by animals.

The type of feed is not particularly limited, and feed commonly used in the art can be used. Non-limiting examples of the feed include plant feed such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, gourds or grain by-products; Examples include animal feeds such as proteins, inorganic substances, fats and oils, mineral oils, oils and fats, single-cell proteins, zooplanktons or foods. These may be used alone or in combination of two or more types.

The pharmaceutical composition for preventing or treating osteoporosis containing the wheat bran extract of the present invention exhibits excellent osteoclast differentiation inhibition and osteoblast formation ability, and can therefore be provided as a composition for preventing, improving or treating osteoporosis.

Figure 1 shows the results of comparing the effects of wheat bran water extract and wheat bran alcohol extract on the inhibition of differentiation of osteoclasts depending on their concentration.
Figure 2 shows the results of comparing the effects of different concentrations of wheat bran water extract and wheat bran alcohol extract on promoting differentiation of osteoblasts.

Hereinafter, the present invention will be described in more detail through examples. These examples are for illustrating the present invention in more detail, and the scope of the present invention is not limited by these examples.

Example 1. Wheat bran extract raw material

We conducted an analysis of the tocopherol, anthocyanin, starch, and non-starch contents of short and bran, which are by-products generated when milling Saegeumgang wheat, Baekjung wheat, and Ariheuk, which are the major wheat varieties currently being expanded in Korea. Among these, Ari black bran was used as a raw material for extract production.

Example 2. Preparation of wheat bran extract

Example 2-1. Preparation of wheat bran water extract

First, 2 L of distilled water was added to 1 kg of Ari black bran, extracted by stirring for 24 hours at room temperature, and the process of filtering with filter paper was repeated three times, and each filtrate was collected. All collected filtrates were collected and concentrated using a vacuum concentrator to obtain a wheat bran water extract.

Example 2-2. Preparation of wheat bran spirit extract

Next, wheat bran alcohol extract was obtained by the same process, except that alcohol was used instead of distilled water.

Example 3. Comparison of the inhibitory effect on osteoclast differentiation depending on the extract solvent of wheat bran

It was confirmed whether the wheat bran extract obtained in Example 2 exhibited the ability to inhibit differentiation of osteoclasts.

Specifically, osteoclast precursor cells were treated with the wheat bran water extract and alcohol extract obtained in Example 1 at various concentrations (1, 10, 30, 100, or 300 μg/ml), and then treated with RANKL (an osteoclast differentiation-inducing cytokine). Differentiation was induced by adding 10 ng/ml), and after 4 days, tartrate resistant acid phosphatase (TRAP), a molecular marker related to osteoclast differentiation, was stained and observed under an optical microscope (Figure 1). At this time, the activity of TRAP was performed by measuring the absorbance at 405 nm using Tartrate resistant acid phosphatase Reagents from Sigma Aldrich.

As a result, as shown in Figure 1, the effect of suppressing osteoclast activity was confirmed even when treated with 10 μg/ml of wheat bran water extract, and at a concentration of 30 μg/ml or more, the activity of osteoclasts was increased by about 90%. The suppressing effect could be confirmed.

Example 4. Comparison of the effect of promoting osteoblast differentiation according to the extract solvent of wheat bran

It was confirmed whether the wheat bran extract obtained in Example 2 exhibited the ability to promote differentiation of osteoblasts.

Specifically, the wheat bran water extract and alcohol extract obtained in Example 1 at various concentrations (1, 10, 30, 100 or 300 μg/ml) to C2C12, an osteoblast progenitor cell, and BMP-2 (an osteoblast differentiation-inducing cytokine) 100 ng/ml) was simultaneously treated to induce differentiation into osteoblasts. To confirm the formation and differentiation ability of osteoblasts, alkaline phosphatase (ALP), a molecular marker related to osteoblast differentiation, was stained and observed under an optical microscope (Figure 2). At this time, the activity of ALT was measured using Alkaline Phosphatase Reagents from Thermo Fisher Scientific.

As a result, as shown in Figure 2, it was confirmed that approximately 50% of osteoblasts were formed when treated with 30 μg/ml of wheat bran alcohol extract.

From the above description, those skilled in the art to which the present invention pertains will understand that the present invention can be implemented in other specific forms without changing its technical idea or essential features. In this regard, the embodiments described above should be understood in all respects as illustrative and not restrictive. The scope of the present invention should be construed as including the meaning and scope of the patent claims described below rather than the detailed description above, and all changes or modified forms derived from the equivalent concept thereof are included in the scope of the present invention.

Claims (8)

A pharmaceutical composition for preventing or treating osteoporosis, comprising a wheat bran extract. According to clause 1,
A pharmaceutical composition, wherein the wheat variety is Ari black. According to clause 1,
The wheat bran extract is a pharmaceutical composition obtained by extracting wheat bran with one or more solvents selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof. According to clause 1,
A pharmaceutical composition, wherein the wheat bran extract inhibits differentiation of osteoclasts. According to clause 1,
A pharmaceutical composition wherein the wheat bran extract promotes differentiation of osteoblasts. A method for preventing or treating osteoporosis, comprising administering the pharmaceutical composition of any one of claims 1 to 5 to an entity other than a human. A food composition for preventing or improving osteoporosis, comprising a wheat bran extract. A feed composition for preventing or improving osteoporosis, comprising a wheat bran extract.