Bone formation promoter and oral composition for promoting bone formation

Abstract

To discover, from among safe natural products, one having the action of promoting bone formation, and provide a bone formation promoter containing the same as an active ingredient, and an oral composition for promoting bone formation that comprises the component.SOLUTION: A bone formation promoter contains, as an active ingredient, black ginger extract. An oral composition for promoting bone formation comprises black ginger extract.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an agent for promoting bone formation and an oral composition for promoting bone formation. [Background technology]

[0002] Bone is a tissue whose main components are hydroxyapatite, a type of calcium phosphate, and type I collagen, and plays an important role not only in supporting our bodies but also in maintaining blood calcium levels and producing blood. Bones are formed by calcification of osteoblasts, which are differentiated from mesenchymal stem cells, via bone matrix proteins and matrix vesicles, and are then resorbed (destroyed) by osteoclasts. In this way, bone formation and resorption (destruction) are constantly repeated (bone remodeling), and normal bone density is maintained by a well-balanced metabolism of this bone (Non-Patent Document 1).

[0003] In recent years, the aging of society and changes in dietary habits have disrupted the balance of bone remodeling, and the number of patients with bone diseases has been reported to increase. Osteoporosis, a representative example of bone-related disease, is a disease caused mainly by increased bone resorption leading to a decrease in bone density. In addition to osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontal disease are also bone-related diseases closely related to abnormalities in bone remodeling.

[0004] Therefore, it is believed that by promoting bone formation and correcting abnormalities in bone remodeling, it is possible to prevent, treat and improve bone-related diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis and periodontal disease. Royal jelly, glucosamine and chondroitin sulfate are known to promote bone formation (Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2019-62931 A [Non-patent literature]

[0006] [Non-Patent Document 1] Journal of the Japanese Society of Nephrology, 2014;56(8):1188-1195. Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention aims to find a highly safe natural product that has the effect of promoting bone formation, and to provide a bone formation promoter that contains this product as an active ingredient, as well as an oral composition for promoting bone formation that contains this ingredient. [Means for solving the problem]

[0008] In order to solve the above problems, the bone formation promoter according to the present invention is characterized in that it contains black ginger extract as an active ingredient. Also, the oral composition for promoting bone formation according to the present invention is characterized in that it contains black ginger extract. Effect of the Invention

[0009] According to the present invention, by using black ginger extract derived from natural products as an active ingredient, it is possible to provide a bone formation promoter that is excellent in effectiveness and is highly safe. Furthermore, by incorporating black ginger extract, it is possible to provide an oral composition for promoting bone formation that is excellent in the above-mentioned effects. [Brief description of the drawings]

[0010] [Figure 1] 1 is a graph showing the results of a bone formation promoting effect test. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Hereinafter, an embodiment of the present invention will be described. The bone formation promoter according to the present embodiment contains black ginger extract as an active ingredient. The oral composition for promoting bone formation according to the present embodiment contains black ginger extract.

[0012] Black ginger is a plant of the genus Kaempferia in the family Zingiberaceae, and its scientific name is Kaempferia parviflora. Black ginger is distributed in Southeast Asia, such as Thailand, and is easily available in this region.

[0013] The black ginger extract can be easily obtained by a method generally used for plant extraction. The black ginger extract includes an extract of black ginger, a dilution or concentrate of the extract, a dried product obtained by drying the extract, or a crude or purified product thereof.

[0014] There are no particular limitations on the constituent parts of black ginger that can be used as the extraction raw material, and they can be appropriately selected depending on the purpose. For example, the rhizome of black ginger can be used.

[0015] The above-mentioned plant extract can be obtained by drying the extraction raw material, and then subjecting it to extraction with an extraction solvent, either directly or after crushing using a crusher. Drying can be performed in the sun or using a commonly used dryer. The raw material can also be used after pretreatment such as degreasing with a non-polar solvent such as hexane or benzene. By performing pretreatment such as degreasing, black ginger can be efficiently extracted with a polar solvent.

[0016] As the extraction solvent, it is preferable to use a polar solvent, such as water or a hydrophilic organic solvent, which is preferably used alone or in combination of two or more at room temperature or at a temperature below the boiling point of the solvent.

[0017] Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, etc., as well as water that has been subjected to various treatments. Treatments that can be applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, etc. Therefore, water that can be used as an extraction solvent in this embodiment also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered physiological saline, etc.

[0018] Examples of hydrophilic organic solvents that can be used as the extraction solvent include lower aliphatic alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones, such as acetone and methyl ethyl ketone; and polyhydric alcohols having 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin.

[0019] When a mixture of two or more polar solvents is used as an extraction solvent, the mixing ratio can be adjusted appropriately. For example, when a mixture of water and a lower aliphatic alcohol is used as an extraction solvent, the mixing ratio of water to lower aliphatic alcohol is preferably 9:1 to 1:9 (volume ratio), and more preferably 7:3 to 2:8 (volume ratio). When a mixture of water and a lower aliphatic ketone is used, the mixing ratio of water to lower aliphatic ketone is preferably 9:1 to 2:8 (volume ratio), and when a mixture of water and a polyhydric alcohol is used, the mixing ratio of water to polyhydric alcohol is preferably 8:2 to 1:9 (volume ratio).

[0020] In the present invention, there is no need to employ a special extraction method for extracting a substance having bone formation promoting activity from black ginger, which is the extraction raw material, and the extraction can be carried out at room temperature or under reflux heating using any extraction device.

[0021] Specifically, the rhizome of black ginger as the extraction raw material is put into a treatment tank filled with an extraction solvent, and then left to stand for 30 minutes to 2 hours while stirring occasionally as necessary to elute the soluble components, and then filtered to remove solids, and the extraction solvent is distilled off from the obtained extract liquid, and dried to obtain the extract. The amount of the extraction solvent is usually 5 to 15 times (by mass) the amount of the extraction raw material. When water is used as the extraction solvent, the extraction conditions are usually 50°C to 95°C for about 1 to 4 hours. When a mixed solvent of water and ethanol is used as the extraction solvent, the extraction conditions are usually 40°C to 90°C for about 30 minutes to 4 hours. The extract obtained by extraction with a solvent can be used as it is as the bone formation promoter of the present invention, as long as the extraction solvent is highly safe.

[0022] The obtained black ginger extract may be subjected to treatments such as dilution, concentration, drying, purification, etc. according to conventional methods to obtain a diluted or concentrated extract, a dried product of the extract, or a crude or purified product thereof.

[0023] The black ginger extract obtained as described above has excellent bone formation promoting activity and can be used as an active ingredient of a bone formation promoter. The bone formation promoter according to the present embodiment can be used in a wide range of applications such as medicines, quasi-drugs, cosmetics, food and beverages, etc.

[0024] The bone formation promoter according to this embodiment may consist of black ginger extract alone, or may be a formulation of a composition containing black ginger extract.

[0025] The bone formation promoter according to this embodiment can be formulated into any dosage form, such as powder, granules, tablets, liquid, etc., according to a conventional method using a pharma- ceutically acceptable carrier such as dextrin, cyclodextrin, or any other auxiliary agent. In this case, examples of auxiliary agents that can be used include excipients, binders, disintegrants, lubricants, stabilizers, flavorings, and odorants. The bone formation promoter can be used by being blended with other compositions (e.g., external preparations, oral compositions, etc.), and can also be used as tablets, capsules, etc.

[0026] When the bone formation promoter according to this embodiment is formulated, the content of the black ginger extract is not particularly limited and can be appropriately set depending on the purpose.

[0027] In addition, in the bone formation promoter of this embodiment, other natural extracts having bone formation promoting activity can be mixed with the black ginger extract and used as active ingredients, if necessary.

[0028] The bone formation promoter of this embodiment can be administered to a patient by oral administration, transdermal administration, etc., and a method suitable for prevention, treatment, etc. can be appropriately selected depending on the type of disease.

[0029] Furthermore, the dosage of the bone formation promoter of this embodiment may be increased or decreased as appropriate depending on the type and severity of the disease, individual differences between patients, the administration method, administration period, and the like.

[0030] The bone formation promoter according to the present embodiment can be used for the prevention, treatment, or amelioration of bone-related diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontal disease through the bone formation promoting effect of the black ginger extract, which is an active ingredient. However, the bone formation promoter according to the present embodiment can be used for all applications in which it is meaningful to exert the bone formation promoting effect in addition to these applications.

[0031] Furthermore, since the bone formation promoter according to this embodiment has an excellent bone formation promoting effect, it can be suitably used as a reagent for research into the mechanism of action thereof.

[0032] The bone formation promoter of the present embodiment has an excellent bone formation promoting effect, and is therefore suitable for incorporation into, for example, an external preparation or an oral composition. In this case, the black ginger extract may be incorporated as is, or a bone formation promoter formulated from the black ginger extract may be incorporated.

[0033] Here, topical preparations are not limited to specific classifications and include a wide range of drugs, quasi-drugs, skin cosmetics, etc. that are used transdermally.

[0034] The amount of black ginger extract in the topical preparation can be adjusted as appropriate depending on the type of topical preparation, but a suitable blending rate is 0.0001 to 10% by mass, and a particularly suitable blending rate is 0.001 to 1% by mass.

[0035] The oral composition refers to a composition that is unlikely to cause harm to human health and is taken orally or by administration through the digestive tract in normal social life, and is not limited to administrative classifications such as food, medicine, and quasi-drug. Therefore, the "oral composition" in this embodiment broadly includes general food, feed, health food, health functional food (specified health food, nutrient functional food, functional food), quasi-drug, medicine, etc. that are taken orally. The oral composition according to this embodiment is preferably an oral composition that can display the favorable effects of black ginger extract on the oral composition or its packaging, and is particularly preferably a health functional food (specified health food, nutrient functional food, functional food), quasi-drug, or medicine.

[0036] By incorporating black ginger extract or a bone formation promoter formulated from black ginger extract into an oral composition, it is possible to make the oral composition suitable for bone formation promotion. The above-mentioned action is preferable because the action effect is easily exerted by being imparted to the oral composition.

[0037] When black ginger extract is added to an oral composition, the amount of black ginger extract added can be appropriately changed in consideration of the purpose of use, symptoms, sex, etc., but it is preferable to adjust the amount of extract to be ingested by an adult per day to about 1 to 1000 mg, taking into consideration the general intake of the oral composition to be added. When the oral composition to be added is in the form of granules, tablets, or capsules, the amount of black ginger extract added is usually 0.1 to 100% by mass or more, preferably 5 to 100% by mass or more, based on the oral composition to be added.

[0038] When producing the oral composition of this embodiment, any auxiliary agent can be added, for example, sugars such as dextrin, starch, etc.; proteins such as gelatin, soy protein, corn protein, etc.; amino acids such as alanine, glutamine, isoleucine, etc.; polysaccharides such as cellulose, gum arabic, etc.; fats and oils such as soybean oil, medium-chain fatty acid triglyceride, etc., to form an oral composition in any shape.

[0039]

[0036] Although there is no particular limitation, specific examples of oral compositions that can incorporate the black ginger extract include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (including concentrated concentrates and powders for adjusting these beverages); frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, harusame, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; sweets such as candy, chewing gum, candies, gum, chocolate, tablet candies, snacks, biscuits, jellies, jams, creams, and baked goods; processed seafood and livestock foods such as kamaboko, ham, and sausages; dairy products such as processed milk and fermented milk; oils and fats and oil-based processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; seasonings such as sauces and sauces; soups, stews, salads, side dishes, and pickles; health functional foods in various other forms; tablets, capsules, and drinks. When black ginger extract is incorporated into these oral compositions, commonly used auxiliary raw materials and additives can be used in combination.

[0040] Although the bone formation promoter, topical agent, and oral composition of this embodiment are suitable for use in humans, they can also be used in animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as their respective functional effects are achieved. EXAMPLES

[0041] The present invention will be specifically explained below by showing test examples, but the present invention is not limited to the following examples in any way.

[0042] [Production Example 1] Production of black ginger extract 100 g of crushed rhizomes of black ginger as the raw material for extraction was added to 1000 mL of 60% ethanol by volume, and the mixture was kept at 80°C for 2 hours with gentle stirring, and then filtered. The filtrate was concentrated under reduced pressure at 40°C and further dried in a vacuum dryer to obtain 23.9 g of extract (powder form) (Sample 1).

[0043] [Test Example 1] Bone formation promotion effect test The black ginger extract (sample 1) obtained in Production Example 1 was tested for its bone formation promoting effect as follows.

[0044] Human mesenchymal stem cells (hMSCs, Lonza) were cultured in α-MEM medium (Life Technologies, containing 10% FBS (HyClone), 1% antibiotics (Life Technologies)) at 37°C and 5% CO. 2 The medium was changed every two days.

[0045] 1×10 3hMSCs (passage 5-7) were seeded in a 96-well plate and cultured in the above-mentioned α-MEM medium. After reaching 100% confluence, the medium was replaced with osteogenic differentiation-inducing medium (OS) containing the test sample (sample 1, see Figure 1 for sample concentration). As the osteogenic differentiation-inducing medium, α-MEM medium (containing 10% FBS, 1% antibiotics) containing differentiation factors 10 mM β-glycerophosphate, 100 nM dexamethasone, and 50 μg / ml L-ascorbic acid 2-phosphate was used. As a negative control, α-MEM medium (containing 10% FBS, 1% antibiotics) without differentiation factors (OS(-)) was used. The medium was replaced every 2 days and the cells were cultured for 14 days. For each sample concentration and negative control, the test was performed in duplicate.

[0046] After incubation, the cells were washed with PBS and fixed with 95% ethanol for 10 minutes. Alizarin red staining solution was then added and stained at room temperature for 30 minutes. After staining, the cells were washed several times with distilled water. After confirming calcification by Alizarin red staining, the percentage of the area stained with Alizarin red was calculated by image analysis using Image J. The average percentages for each test concentration and the negative control (repeated 2 times) are shown in Figure 1.

[0047] As shown in FIG. 1, it was confirmed that Sample 1 had an excellent bone formation promoting effect.

[0048] [Formulation example 1] A cream having the following composition was prepared by a conventional method. Black ginger extract (sample 1) 0.05g Sophora root extract 0.1g Scutellaria root extract 0.1g Liquid paraffin 5.0g White beeswax 4.0g Squalane 10.0g Cetanol 3.0g Lanolin 2.0g Stearic acid 1.0g Polyoxyethylene sorbitan oleate (20E.O.) 1.5g Glyceryl monostearate 3.0g Oil-soluble licorice extract 0.1g 1,3-butylene glycol 6.0g Methyl paraoxybenzoate 1.5g Fragrance 0.1g Purified water Remainder (total amount is 100g)

[0049] [Formulation example 2] According to the composition below, a milky lotion was prepared by a conventional method. Black ginger extract (sample 1) 0.10g Jojoba oil 4.00g 1,3-butylene glycol 3.00g Arbutin 3.00g Polyoxyethylene cetyl ether (20E.O.) 2.50g 2.00g olive oil Squalane 2.00g Cetanol 2.00g Glyceryl monostearate 2.00g Polyoxyethylene sorbitan oleate (20E.O.) 2.00g Methyl paraoxybenzoate 0.15g Stearyl glycyrrhetinate 0.10g Phellodendron Bark Extract 0.10g Dipotassium glycyrrhizinate 0.10g Ginkgo leaf extract 0.10g Conchiolin 0.10g Phellodendron bark extract 0.10g Chamomile extract 0.10g Fragrance 0.05g Purified water Remainder (total amount is 100g)

[0050] [Formulation example 3] A beauty essence having the following composition was prepared by a conventional method. Black ginger extract (sample 1) 0.001g Chamomile extract 0.1g Carrot extract 0.1g Xanthan gum 0.3g Hydroxyethylcellulose 0.1g Carboxyvinyl polymer 0.1g 1,3-butylene glycol 4.0g Dipotassium glycyrrhizinate 0.1g Glycerin 2.0g Potassium hydroxide 0.25g Fragrance 0.01g Preservative (methyl parahydroxybenzoate) 0.15g Ethanol 2.0g Purified water Remainder (total amount is 100g)

[0051] [Formulation example 4] Tablets having the following composition were prepared by a conventional method. Black ginger extract (sample 1) 5.0mg Dolomite (containing 20% ​​calcium and 10% magnesium) 83.4mg Casein phosphopeptide 16.7mg Vitamin C 33.4mg Maltitol 136.8mg Collagen 12.7mg Sucrose fatty acid ester 12.0mg

[0052] [Formulation example 5] An oral liquid preparation having the following composition was produced by a conventional method. <Composition in 1 ampoule (100 mL)> Black ginger extract (sample 1) 0.5% by mass Sorbitol 12.0% by mass Sodium benzoate 0.1% by mass Fragrance 1.0% by mass Calcium sulfate 0.5% by mass Purified water remainder (100% by mass) [Industrial Applicability]

[0053] The bone formation promoter of the present invention can greatly contribute to the prevention, treatment, or amelioration of bone-related diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontal disease.

Claims

1. 1. A promoter for promoting bone formation by osteoblasts, comprising an extract from the rhizome of black ginger as an active ingredient.

2. An oral composition for promoting bone formation by osteoblasts, comprising an extract from the rhizome of black ginger.

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