JP2024009190A - Bone fortifier dietary supplements - Google Patents

Abstract

To provide bone fortifier dietary supplements with a high osteogenesis promoting effect.SOLUTION: A bone fortifier dietary supplement is characterized by containing as an active ingredient isoflavone, and specific components of plant materials, such as Hordeum vulgare, Ipomoea batatas, Peucedanum japonicum, Pinus, Terminalia, Cocos nucifera, Aristotelia Chilensis, and Brassica oleracea.SELECTED DRAWING: Figure 1

Description

The present invention relates to a bone-strengthening agent, and more particularly, to a bone-strengthening agent containing isoflavones and certain other ingredients as active ingredients.

In recent years, osteoporosis has been on the rise, especially among elderly women. This osteoporosis is said to be caused by poor absorption of calcium from the intestines and decreased secretion of female hormones with age.

On the other hand, soy isoflavones, also called phytoestrogens, have estrogen-like effects on female hormones, and are known to promote bone formation and suppress bone resorption (bone destruction). .

Examples of such preparations using soy isoflavones include periodontal disease prevention preparations characterized by containing soy isoflavone aglycones (see Patent Document 1), and preparations characterized by containing fermented plant extracts and isoflavones. A bone strengthening agent containing a milk-derived basic protein fraction and/or a milk-derived basic protein fraction decomposition product and soybean isoflavones as active ingredients (see Patent Document 2) (see document 3) has been proposed.

Japanese Patent Application Publication No. 2002-121146 JP2012-240946A Japanese Patent Application Publication No. 2013-184959

An object of the present invention is to provide a bone strengthening agent that has a high osteogenesis promoting effect.

The present inventors conducted extensive research and investigation into the bone-strengthening ability of isoflavones, and found that a combination of isoflavones and certain other components can provide a high bone formation promoting effect. It's arrived. That is, it has been found that by combining isoflavones with certain other components that have little or low bone formation promoting ability, it is possible to synergistically improve the bone formation promoting ability.

That is, the present invention relates to a bone strengthening agent characterized by containing isoflavones and at least one component selected from the group consisting of (a) to (e) below as active ingredients.
(a) At least one type of plant material selected from barley, sweet potato, long-term grass, pine, terminaria, coconut, maqui berry, and kale (b) At least one type of additive selected from reduced maltose and calcium stearate (c) Asparagine , cysteine, glutamine, glutamic acid, glycine, leucine, lysine, phenylalanine, serine, and valine (d) polyphenol consisting of chlorogenic acid (e) vitamin B1, vitamin B2, vitamin B6, vitamin B12, At least one vitamin/mineral selected from sodium pantothenate, niacin, folic acid, vitamin K, magnesium, iron, selenium, and calcium.

The bone strengthening agent of the present invention may be obtained by adding an active ingredient consisting of isoflavones and at least one component selected from the group consisting of (a) to (e).

In the bone strengthening agent of the present invention, the blending mass ratio of isoflavones and other active ingredients is preferably in the range of 0.5:1 to 70:1.
Moreover, the bone strengthening agent of the present invention is preferably in the form of a tablet, capsule, powder, granule, or liquid.

The present invention also relates to a bone strengthening method (excluding medical treatment) characterized by ingesting the bone strengthening agent of the present invention.

According to the bone strengthening agent of the present invention, a high bone formation promoting effect can be obtained and bones can be strengthened.

It is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + plant material) of the present invention is applied to an osteoblast cell line (MC3T3-E1). The case using grass and pine is shown. It is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + plant material) of the present invention is applied to an osteoblast cell line (MC3T3-E1). The case is shown below. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavones + additives) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses reduced maltose as an additive, and the graph on the right uses calcium stearate as an additive. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + amino acid) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses asparagine as the amino acid, and the graph on the right uses cysteine as the amino acid. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + amino acid) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses glutamine as the amino acid, and the graph on the right uses glutamic acid as the amino acid. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + amino acid) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses glycine as the amino acid, and the graph on the right uses leucine as the amino acid. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + amino acid) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses lysine-hydrochloride as the amino acid, and the graph on the right uses phenylalanine as the amino acid. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + amino acid) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses serine as the amino acid, and the graph on the right uses valine as the amino acid. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + polyphenol) of the present invention is applied to an osteoblast cell line (MC3T3-E1), using chlorogenic acid as the polyphenol. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavones + vitamins and minerals) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The left graph uses vitamin B1 as the vitamin, and the right graph uses vitamin B2 as the vitamin. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavones + vitamins and minerals) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The left graph uses vitamin B6 as the vitamin, and the right graph uses vitamin B12 as the vitamin. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavones + vitamins and minerals) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses sodium pantothenate as the vitamin, and the graph on the right uses niacin as the vitamin. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavones + vitamins and minerals) of the present invention was applied to an osteoblast cell line (MC3T3-E1). The graph on the left uses folic acid as the vitamin, and the graph on the right uses vitamin K as the vitamin. It is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + vitamins and minerals) of the present invention is applied to an osteoblast cell line (MC3T3-E1). , the case using serine is shown. It is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + vitamins and minerals) of the present invention is applied to an osteoblast cell line (MC3T3-E1). From the left, the minerals are eggshell calcium, The case using seaweed calcium and fish calcium is shown. FIG. 2 is a diagram showing the results of Runx2 gene expression when the bone strengthening agent (isoflavone + kale) of the present invention was applied to an osteoblast cell line (MC3T3-E1).

The bone strengthening agent of the present invention is characterized in that it contains isoflavones and at least one component selected from the group consisting of (a) to (e) below (hereinafter sometimes referred to as other components) as active ingredients. shall be. The bone-strengthening agent of the present invention has a high ability to promote bone formation, strengthens bones through an increase in bone mass, and can thereby prevent and treat osteoporosis.

[Isoflavone]
Isoflavones, which are active ingredients of the bone strengthening agent of the present invention, are flavonoid compounds that are abundantly contained in leguminous plants, particularly soybeans, and soybean isoflavones derived from soybeans are preferred as the isoflavones in the present invention. Isoflavones may be aglycones or glycosides. In addition, isoflavones may be purified or may be a mixture of raw materials (for example, soybeans) with other components. Soybean isoflavones are commercially available, and commercially available products can be used.

[Other ingredients]

(a) Plant material In the bone strengthening agent of the present invention, at least one plant material selected from barley, sweet potato, long-term grass, pine, terminaria, coconut palm, maqui berry, and kale is used as an active ingredient along with isoflavones. is preferred.

These plant materials may be any part of the plant, such as leaves, stems, roots, flowers, fruits, trunks, branches, etc., and may include the plant materials themselves (including dried materials), crushed products, and squeezed juice. , extracts, and other processed plant materials can be used. Examples of the pulverized product include powder, granules, and the like. The squeezed juice or extract may be in liquid form, but it can also be used in the form of a paste or dry powder. The extract can be obtained by extraction using an appropriate solvent, and examples of the solvent that can be used include water (hot water), ethanol, and aqueous ethanol. Commercially available plant materials can be used as these plant materials.

As the barley, two-row barley, six-row barley, etc. can be used. The parts used as the plant material of the present invention are preferably stems and leaves, with young leaves being particularly preferred.

Sweet potato refers to a plant belonging to the Convolvulaceae family, and is generally called sweet potato. The varieties of sweet potato are not particularly limited, and examples include Suio, Joy White, Koganesengan, Shiro Yutaka, Sweet Mustache, and Ayamurasaki. The parts used as the plant material of the present invention are preferably stems and leaves, with young leaves being particularly preferred.

Chomeiso is a perennial plant also called Botanbofuu that belongs to the Apiaceae family. The parts used as the plant material of the present invention are preferably leaves and roots.

Examples of the pine include Pinus Martima, larch, Japanese black pine, Japanese red pine, and among these, Pinus Martima, which is rich in proanthocyanidins, is preferred. The part used as the plant material of the present invention is preferably bark, and extracts obtained from pine bark are particularly preferred. In addition to proanthocyanidins, this extract contains oligomeric proanthocyanidins at a high concentration, and preferably contains 20% by mass or more of oligomeric proanthocyanidins based on the dry mass of the extract.

Examples of Terminalia include Terminalia bellirica (belerica), Terminalia catappa, Terminalia tomentosa, Terminalia citrina, Terminalia phellocarpa, and Terminalia phellocarpa. These include Minalia coplandii, Terminalia brassi, Terminalia ivorensis, Terminalia superba, Terminalia arjuna, and Terminalia chebula. Among them, Terminalia bellirica (belerica) and Terminalia chebula are preferred. The part used as the plant material of the present invention is preferably a fruit.

Coco palm is a plant of the palm family, and the fruit (endosperm) is preferable as the part used as the plant material of the present invention.

Maqui berry is a plant of the Portonaceae family that is native to Chilean Patagonia, and its scientific name is Aristotellia chilensis. The part used as the plant material of the present invention is preferably a fruit.

Kale is a Brassicaceae plant, and leaves and stems are preferable as the parts used as the plant material of the present invention. Specifically, preferred are dried and pulverized kale, dried and powdered kale slurry or squeezed juice, and extracts obtained from kale or its dried product. In particular, it is preferable for kale to be subjected to treatments such as drying and extraction immediately after harvesting. If it takes time to process, it is preferable to store the kale by storage means commonly used by those skilled in the art, such as low temperature storage, to prevent deterioration of the quality of the kale. The variety of kale is not particularly limited, and various types of kale such as kitchen kale, tree kale, bush kale, mallow kale, collard, and green leaf kale can be used.

(b) Additives In the bone strengthening agent of the present invention, it is preferable to use at least one additive selected from reduced maltose and calcium stearate as an active ingredient together with isoflavones. Reduced maltose and calcium stearate are additives used in the manufacture of tablets and the like, and reduced maltose is usually used as an excipient and calcium stearate as a lubricant.

(c) Amino acids In the bone strengthening agent of the present invention, in addition to isoflavones, at least one amino acid (salt ) is preferably used. Examples of the salt include sodium salt, hydrochloride, and the like.

(d) Polyphenol In the bone strengthening agent of the present invention, it is preferable to use polyphenol consisting of chlorogenic acid as an active ingredient together with isoflavone.

(e) Vitamins and minerals In addition to isoflavones, the bone strengthening agent of the present invention contains vitamin B1, vitamin B2, vitamin B6, vitamin B12, sodium pantothenate, niacin, folic acid, vitamin K, magnesium, iron, It is preferable to use at least one vitamin/mineral selected from selenium and calcium. Note that iron, selenium, magnesium, and calcium as minerals in the present invention include the form of compounds containing these metals.

The bone strengthening agent of the present invention is not particularly limited as long as it contains isoflavones and other predetermined components and can be distinguished from other products in that it is used for bone strengthening, such as The scope of the present invention includes products according to the present invention that are labeled to have a bone-strengthening effect (bone formation promoting effect) on any of the main body, packaging, instruction manual, or promotional material. For example, so-called health foods such as pharmaceuticals (including quasi-drugs), foods for specified health uses, foods with nutritional function claims, and functional foods whose efficacy has been approved by designated organizations such as foods with nutritional function claims, feed, etc. can be mentioned. Examples of so-called health foods include those with labels such as "for maintaining bone health," "for those concerned about bone health," and "preventing bones from becoming brittle."

Examples of the form of the bone strengthening agent of the present invention include tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, pills, and pastes. Agents, cream preparations, caplet preparations, gel preparations, chewable preparations, stick preparations and the like can be mentioned. Among these, tablet, capsule, powder, granule, and liquid forms are particularly preferred. Specifically, examples include packaged beverages filled in plastic bottles, cans, bottles, etc., instant powdered beverages and instant granular beverages that are dissolved in water (hot water), milk, fruit juice, green juice, etc. be able to. These are preferable because they are easy to drink during meals and can enhance palatability.

The content of isoflavones and other ingredients (active ingredients) in the bone strengthening agent of the present invention may be appropriately contained within the range where the effects thereof can be achieved.

Generally, when the bone strengthening agent of the present invention is a medicine or a supplement (tablet, capsule), it is preferable that the active ingredient is contained in an amount of 0.01 to 100% by mass of the total on a dry mass basis. It is more preferably contained in an amount of 0.1 to 85% by mass, and even more preferably 0.5 to 70% by mass.

When the bone strengthening agent of the present invention is a packaged beverage (liquid), it is preferable that the active ingredient is contained in an amount of 0.01 to 15% by mass, and preferably 0.03 to 12.5% by mass of the total in terms of dry mass. The content is more preferably 0.05 to 10% by mass, and even more preferably 0.05 to 10% by mass.

Furthermore, when the bone strengthening agent of the present invention is an instant powder drink (powder) or instant granule drink (granule), the active ingredient is contained in an amount of 0.1 to 80% by mass of the total in terms of dry mass. The content is preferably from 0.5 to 70% by mass, and even more preferably from 1 to 60% by mass.

In order to more effectively exhibit the effects of the present invention, it is preferable that the active ingredient contains 80% or more of the total bone strengthening agent of the present invention (excluding water) in terms of dry mass, and preferably contains 90% or more. It is more preferable that the content is 95% or more, and it is particularly preferable that the content is 100%. Furthermore, when the bone strengthening agent of the present invention contains any of the components (a) to (e), it is preferable that the contained components consist only of the active ingredients of the present invention. That is, when the bone strengthening agent of the present invention contains component (a) (plant material), for example, it is configured so that it does not contain plant materials other than barley, sweet potato, long-term grass, pine, terminaria, coconut palm, maqui berry, and kale. It is preferable to do so.

Although there is no particular restriction on the amount of the bone strengthening agent of the present invention to be ingested, from the perspective of exhibiting the effects of the present invention more markedly, the amount of active ingredient ingested per day should be 0.1 mg/day or more. It is preferable to ingest it, more preferably at least 1 mg/day, even more preferably at least 10 mg/day. The upper limit is not particularly limited, but is, for example, 8 g/day, preferably 4 g/day. Further, it is preferable that the amount of isoflavones ingested by ingesting the bone strengthening agent of the present invention is 30 mg/day or less (in terms of aglycone).

The bone strengthening agent of the present invention can be stored in one container or divided into a plurality of containers, for example, 2 to 3, so that the daily intake amount is the above-mentioned intake amount.

The blended mass ratio of isoflavones and other components is preferably in the range of 0.5:1 to 70:1, more preferably in the range of 0.75:1 to 60:1, in terms of dry mass. , more preferably in the range of 1:1 to 60:1, particularly preferably in the range of 1:1 to 50:1. When the blending ratio of isoflavones and other components is within the above range, the effects of the present invention can be more effectively exhibited.

The bone strengthening agent of the present invention can be manufactured by a known formulation method by adding ingredients other than the orally acceptable active ingredient, if necessary.

In addition, examples of the bone strengthening agent of the present invention include bone strengthening foods containing active ingredients as well as bone strengthening foods obtained by adding active ingredients to foods. Examples include foods in which active ingredients are added to foods that normally do not contain active ingredients. The active ingredients may be added separately, simultaneously, or together with other ingredients other than the active ingredients.

Examples of the bone-strengthening food of the present invention include drinks such as carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, smoothies, and green juice; frozen desserts such as ice cream, ice sorbet, and shaved ice; Noodles such as noodles and instant noodles; Confectionery such as candy, candies, gum, chocolate, tablets, snack foods, biscuits, jellies, jams, creams, baked goods, and bread; Fishery and livestock processed foods such as kamaboko, ham, and sausages. ; Dairy products such as processed milk, fermented milk, and yogurt; Oils and fats and processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressing; Seasonings such as sauces and soy sauce; Curry, stew, and oyakodon Examples include retort pouch foods such as porridge, porridge, Chinese rice bowl, katsudon, tempura bowl, beef bowl, hashed rice, omelet rice, oden, marbodoff, gyoza, shumai, hamburger steak, meatballs, various sauces, and various soups. .

The bone strengthening method of the present invention is characterized by ingesting the bone strengthening agent of the present invention described above, but does not include medical treatment. Examples of the method of the present invention include a method of strengthening bones by providing the bone-strengthening food of the present invention in restaurants and other eating establishments.

Hereinafter, the present invention will be explained based on examples.
[Example 1]
5 × 10 ³ / WeLL (MC3T3 -E1) of boring cell stocks (MC3T3 -E1) cultured in culture (MEMA; ALPHA ModifiCation OF EAGLE's Minum ESSENTIAL MEDIA, 10 % FBS, 1 % PS) Squeezed to 96WELL PLATE in the amount .

Then, 0.1 mL of 0.5 μg/mL isoflavones or a solution prepared by dissolving other components shown in Tables 1 to 5 at predetermined concentrations was added, and cultured for 48 hours. Runx2 gene expression was measured by real-time PCR. (It was confirmed in advance by WST that the concentration was such that 90% or more of the cells would survive compared to the control). Note that the Runx2 gene is a transcription factor essential for osteoblast differentiation, and is known to induce osteoblast differentiation and promote bone formation.

The results are shown in Tables 1 to 5 and FIGS. 1 to 15. The graphs in the figure are, from left to right, "Control - (no addition)", "Control + (addition of 0.5 μg/mL isoflavone alone)", "Addition of other components alone", "0.5 μg/mL isoflavone +Addition of other ingredients” is shown. Further, the numerical value in the explanation at the bottom of the graph indicates the sample concentration; for example, "250-" for barley in the graph of FIG. 1 indicates barley 250 (μg/mL). The concentration unit of added components is μg/mL in all graphs. The graph is expressed as a relative value when the value of control + is set to 1.

For barley, dry and ground powder of young leaves was used.
For sweet potato, dried crushed powder of young leaves was used.
For Chomeisou, dried and ground powder of leaves was used.
For pine, a hot water extract (dry powder) of French maritime pine bark was used.
For Terminalia, a hot water extract (dry powder) of the fruit was used.
As for the coconut, commercially available coconut milk was dried and the oil content was removed.
For Maqui berry, a commercially available dried fruit powder was used.
For kale, dried and ground powder of leaves was used.
For mugwort, finely ground powder of fresh leaves was used.

As shown in Tables 1 to 5 and FIGS. 1 to 15, the combination of isoflavones and specific other components of the present invention synergistically increased the expression level of the Runx2 gene in osteoblast cell lines. Therefore, according to the bone strengthening agent of the present invention, bone formation is promoted and bones can be effectively strengthened.

[Example 2] (Manufacture of tablets)
Soybean isoflavones 25mg, aspartame 10mg, reduced maltose 50mg, calcium stearate 200mg, cysteine 10mg, lysine hydrochloride 5mg, phenylalanine 5mg, serine 0.1mg, niacin 5mg, folic acid 0.05mg, vitamin K 0.1mg, iron 0.01mg , 0.02 mg of magnesium, 50 mg of maqui berry, 0.2 mg of pine bark extract, and 50 mg of fish calcium were compressed to produce tablets.

[Example 3] (Manufacture of capsules)
Soybean isoflavones 50mg, aspartame 180mg, reduced maltose 50mg, calcium stearate 350mg, cysteine 10mg, lysine hydrochloride 5mg, phenylalanine 5mg, serine 0.1mg, niacin 5mg, folic acid 0.05mg, vitamin K 0.1mg, iron 0.01mg , 0.02 mg of magnesium, 50 mg of coconut, and 0.2 mg of seaweed calcium was encapsulated in soft capsules to produce capsules.

[Example 4] (Production of instant powder 1)
Soy isoflavones 50mg, aspartame 180mg, reduced maltose 200mg, maltose 200mg, calcium stearate 200mg, asparagine 250mg, glutamine 25mg, glutamic acid 25mg, glycine 20mg, leucine 20mg, chlorogenic acid 10mg, vitamin B1 0.1mg, vitamin B2 0.1mg, vitamin B6 0.1mg, vitamin B12 0.05mg, sodium pantothenate 0.05mg, folic acid 0.2mg, vitamin K 0.1mg, indigestible dextrin 2000mg, barley grass powder 2000mg, kale powder 2000mg, Sencha finely ground powder 500mg, 250 mg of shellfish calcium was mixed to produce a powder. This powder had good solubility when dissolved in 100 ml of water.

[Example 5] (Production of instant powder 2)
Soybean isoflavones 100mg, reduced maltose 1000mg, maltose 1200mg, sugar 300mg, indigestible dextrin 2000mg, asparagine 250mg, glutamine 25mg, glutamic acid 25mg, glycine 20mg, leucine 20mg, chlorogenic acid 10mg, vitamin B1 0.1mg, vitamin B2 0.1mg , Vitamin B6 0.1mg, Vitamin B12 0.05mg, Sodium pantothenate 0.05mg, Folic acid 0.2mg, Vitamin K 0.1mg, Sweet potato young leaf powder 2000mg, Kale powder 2000mg, Sencha finely ground powder 500mg, Coral uncalcined calcium 10 mg were mixed to produce a powder.
This powder had good solubility when dissolved in 200 ml of water.

[Example 6] (Manufacture of PET bottle liquid)
Soy isoflavones 75mg, reduced maltose 2500mg, asparagine 350mg, glutamine 50mg, glutamic acid 50mg, glycine 50mg, leucine 20mg, valine 20mg, chlorogenic acid 20mg, vitamin B1 0.2mg, vitamin B2 0.2mg, vitamin B6 0.2mg, vitamin B12 0.2mg, sodium pantothenate 0.1mg, folic acid 0.2mg, vitamin K 0.1mg, barley grass powder 2500mg, sweet potato grass powder 2500mg, long life grass 1000mg, pine bark extract 50mg, Terminalia Berylica 250mg, coral uncalcined A liquid preparation was produced by filling a PET bottle with 500 mg of calcium and 500 ml of water and sealing the bottle.

The bone-strengthening agent of the present invention has a bone-strengthening effect and can be used as an oral preparation, so the industrial utility of the present invention is high.

Claims (1)

A food product characterized by containing isoflavones as an active ingredient for maintaining bone health, and further containing at least one plant material selected from the group consisting of pine bark, terminaria, maqui berry, coconut palm, and sweet potato young leaves. .